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Published by Robert Bruce at August 29th, 2023 , Revised On September 5, 2023

Biology Research Topics

Are you in need of captivating and achievable research topics within the field of biology? Your quest for the best biology topics ends right here as this article furnishes you with 100 distinctive and original concepts for biology research, laying the groundwork for your research endeavor.

Table of Contents

Our proficient researchers have thoughtfully curated these biology research themes, considering the substantial body of literature accessible and the prevailing gaps in research.

Should none of these topics elicit enthusiasm, our specialists are equally capable of proposing tailor-made research ideas in biology, finely tuned to cater to your requirements.

Thus, without further delay, we present our compilation of biology research topics crafted to accommodate students and researchers.

Research Topics in Marine Biology

Impact of climate change on coral reef ecosystems.
Biodiversity and adaptation of deep-sea organisms.
Effects of pollution on marine life and ecosystems.
Role of marine protected areas in conserving biodiversity.
Microplastics in marine environments: sources, impacts, and mitigation.

Biological Anthropology Research Topics

Evolutionary implications of early human migration patterns.
Genetic and environmental factors influencing human height variation.
Cultural evolution and its impact on human societies.
Paleoanthropological insights into human dietary adaptations.
Genetic diversity and population history of indigenous communities.

Biological Psychology Research Topics

Neurobiological basis of addiction and its treatment.
Impact of stress on brain structure and function.
Genetic and environmental influences on mental health disorders.
Neural mechanisms underlying emotions and emotional regulation.
Role of the gut-brain axis in psychological well-being.

Cancer Biology Research Topics

Targeted therapies in precision cancer medicine.
Tumor microenvironment and its influence on cancer progression.
Epigenetic modifications in cancer development and therapy.
Immune checkpoint inhibitors and their role in cancer immunotherapy.
Early detection and diagnosis strategies for various types of cancer.

Cell Biology Research Topics

Mechanisms of autophagy and its implications in health and disease.
Intracellular transport and organelle dynamics in cell function.
Role of cell signaling pathways in cellular response to external stimuli.
Cell cycle regulation and its relevance to cancer development.
Cellular mechanisms of apoptosis and programmed cell death.

Developmental Biology Research Topics

Genetic and molecular basis of limb development in vertebrates.
Evolution of embryonic development and its impact on morphological diversity.
Stem cell therapy and regenerative medicine approaches.
Mechanisms of organogenesis and tissue regeneration in animals.
Role of non-coding RNAs in developmental processes.

Human Biology Research Topics

Genetic factors influencing susceptibility to infectious diseases.
Human microbiome and its impact on health and disease.
Genetic basis of rare and common human diseases.
Genetic and environmental factors contributing to aging.
Impact of lifestyle and diet on human health and longevity.

Molecular Biology Research Topics

CRISPR-Cas gene editing technology and its applications.
Non-coding RNAs as regulators of gene expression.
Role of epigenetics in gene regulation and disease.
Mechanisms of DNA repair and genome stability.
Molecular basis of cellular metabolism and energy production.

Research Topics in Biology for Undergraduates

41. Investigating the effects of pollutants on local plant species.
Microbial diversity and ecosystem functioning in a specific habitat.
Understanding the genetics of antibiotic resistance in bacteria.
Impact of urbanization on bird populations and biodiversity.
Investigating the role of pheromones in insect communication.

Synthetic Biology Research Topics

Design and construction of synthetic biological circuits.
Synthetic biology applications in biofuel production.
Ethical considerations in synthetic biology research and applications.
Synthetic biology approaches to engineering novel enzymes.
Creating synthetic organisms with modified functions and capabilities.

Animal Biology Research Topics

Evolution of mating behaviors in animal species.
Genetic basis of color variation in butterfly wings.
Impact of habitat fragmentation on amphibian populations.
Behavior and communication in social insect colonies.
Adaptations of marine mammals to aquatic environments.

Best Biology Research Topics

Unraveling the mysteries of circadian rhythms in organisms.
Investigating the ecological significance of cryptic coloration.
Evolution of venomous animals and their prey.
The role of endosymbiosis in the evolution of eukaryotic cells.
Exploring the potential of extremophiles in biotechnology.

Biological Psychology Research Paper Topics

Neurobiological mechanisms underlying memory formation.
Impact of sleep disorders on cognitive function and mental health.
Biological basis of personality traits and behavior.
Neural correlates of emotions and emotional disorders.
Role of neuroplasticity in brain recovery after injury.

Biological Science Research Topics:

Role of gut microbiota in immune system development.
Molecular mechanisms of gene regulation during development.
Impact of climate change on insect population dynamics.
Genetic basis of neurodegenerative diseases like Alzheimer’s.
Evolutionary relationships among vertebrate species based on DNA analysis.

Biology Education Research Topics

Effectiveness of inquiry-based learning in biology classrooms.
Assessing the impact of virtual labs on student understanding of biology concepts.
Gender disparities in science education and strategies for closing the gap.
Role of outdoor education in enhancing students’ ecological awareness.
Integrating technology in biology education: challenges and opportunities.

Biology-Related Research Topics

The intersection of ecology and economics in conservation planning.
Molecular basis of antibiotic resistance in pathogenic bacteria.
Implications of genetic modification of crops for food security.
Evolutionary perspectives on cooperation and altruism in animal behavior.
Environmental impacts of genetically modified organisms (GMOs).

Biology Research Proposal Topics

Investigating the role of microRNAs in cancer progression.
Exploring the effects of pollution on aquatic biodiversity.
Developing a gene therapy approach for a genetic disorder.
Assessing the potential of natural compounds as anti-inflammatory agents.
Studying the molecular basis of cellular senescence and aging.

Biology Research Topic Ideas

Role of pheromones in insect mate selection and behavior.
Investigating the molecular basis of neurodevelopmental disorders.
Impact of climate change on plant-pollinator interactions.
Genetic diversity and conservation of endangered species.
Evolutionary patterns in mimicry and camouflage in organisms.

Biology Research Topics for Undergraduates

Effects of different fertilizers on plant growth and soil health.
Investigating the biodiversity of a local freshwater ecosystem.
Evolutionary origins of a specific animal adaptation.
Genetic diversity and disease susceptibility in human populations.
Role of specific genes in regulating the immune response.

Cell and Molecular Biology Research Topics

Molecular mechanisms of DNA replication and repair.
Role of microRNAs in post-transcriptional gene regulation.
Investigating the cell cycle and its control mechanisms.
Molecular basis of mitochondrial diseases and therapies.
Cellular responses to oxidative stress and their implications in ageing.

These topics cover a broad range of subjects within biology, offering plenty of options for research projects. Remember that you can further refine these topics based on your specific interests and research goals.

Frequently Asked Questions

What are some good research topics in biology?

A good research topic in biology will address a specific problem in any of the several areas of biology, such as marine biology, molecular biology, cellular biology, animal biology, or cancer biology.

A topic that enables you to investigate a problem in any area of biology will help you make a meaningful contribution.

How to choose a research topic in biology?

Choosing a research topic in biology is simple.

Follow the steps:

Generate potential topics.
Consider your areas of knowledge and personal passions.
Conduct a thorough review of existing literature.
Evaluate the practicality and viability.
Narrow down and refine your research query.
Remain receptive to new ideas and suggestions.

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For several years, Research Prospect has been offering students around the globe complimentary research topic suggestions. We aim to assist students in choosing a research topic that is both suitable and feasible for their project, leading to the attainment of their desired grades. Explore how our services, including research proposal writing , dissertation outline creation, and comprehensive thesis writing , can contribute to your college’s success.

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150 Actual Biology Research Paper Topics

Table of contents

1 What Is Biology? What Topics Might Biologists Study?
2 How to Choose a Topic for Biology Research Paper?
3.1 15 Developmental Biology Topics For Research
3.2 15 Immune System Biology Research Topics
3.3 15 Cell Biology Research Topics
3.4 15 DNA Research Topics
3.5 15 Molecular Biology Research Topics
3.6 15 Neurobiology Research Topics
3.7 15 Abortion, Human cloning, and Genetic Researches Topics
3.8 15 Environmental and Ecology Topics for Your Research
3.9 15 Plant Pathology Biology Research Topics
3.10 15 Animals Biology Research Topics
3.11 15 Marine Biology Research Topics
3.12 15 Zoology Research Topics
3.13 15 Genetics Research Topics
3.14 15 Biotechnology Research Topics
3.15 15 Evolutionary Biology Research Topics

Biology is one of the most magnetic fields of study these days. If you want to be a biologist or scientist in the future, there is no better time to start than right now. Biology research topics covered in this article will keep you busy and interested. Writing a research paper is one of the best ways to dip your toes into the field. Before doing that, you need to know some good topics for the research paper . They should be suitable for biology students rather than cutting-edge researchers. On Papersowl.com , we provide as many biology research paper examples as possible so that you have a huge choice.

What Is Biology? What Topics Might Biologists Study?

Biology is simply the study of everything that has a form of life. It includes investigations on plants, animals, and everything found in the environment. It is about studying how life forms grow, develop, and interact with each other. Biology essay topics for research encompass all these and more.

This science uncovers many fields where various life forms are studied. It makes sense to look through these fields to help you decide which suits you the best.

Plant Biology research topics are about studying the plants around us. They disclose information about their existence as a part of the ecosystem, their life cycle, resources they can give us, their ability to preserve them from climate changes, and so on. There are many ideas to choose from, but you must focus on a specific one.

Human Biology research topics are all about us. These topics focus on different body parts, such as the human brain, the human immunological system, the nervous system, etc. In addition, you can discuss DNA modifications in humans and explain why genetic disorders occur in your research projects. Various cell research is also common today.

Biology research topics on the environment are in great demand too. For example, climate change is becoming a more significant threat every day. By studying environmental topics in biology for projects and research, we can come up with ways to combat them and preserve ecosystems.

Microbiology research topics delve into things we can’t see. There are trillions of microbes and bacteria all around us. Knowing about them is essential to understanding what makes us sick and how to fight against them. All microbiology research paper topics are pretty complicated yet very engaging to include in your paper research.

Molecular biology topics dive even deeper into the level of atoms and molecules. The various medicines and drugs we take were all created through molecular-biology research. It is one of the areas full of ideas, but there is yet to be much evidence. Science is advancing in this realm but still needs a lot of time. Topics of molecular biology will need days for research only.

Keep in mind that there are more ideas and variations of this science. We offer more examples in further sections of the article about developmental biology, marine biology, evolutionary biology, etc. Explore them and make your writing appealing and meaningful in the eyes of a professor.

How to Choose a Topic for Biology Research Paper?

When choosing a biology project topic, you must be aware of one or more fields of science. Biology research is critical to the present world. By doing research, we can learn more about genetic disorders, immune disorders, mental health, natural disease resistance, etc. Knowing about each of these could save lives in the future.

For those who may not have the time or resources to do their own research, there are research paper writing services that can provide assistance with the project. And we are always here to help you find your own topic among interesting biology research topics. Here we prepared some useful tips to follow.

Tip 1: The level of interest matters Pay attention to one that interests you, and you might have ideas on how to develop the topic. Passion is fundamental in research, after all.
Tip 2: Explore the topic Try to narrow things down a bit. If the topic is too broad, you may not be able to cover all aspects of it in one research paper. If it is too narrow, the paper could end up too short. Analyze the topic and the ways to approach it. By doing so, you can strike a balance between the two.
Tip 3: Discover the recent developments To make your research paper touchable with the present day, you must explore the latest developments in the field. You can find out what kind of research has been done recently by looking at journals. Check out research papers, topics, research articles, and other sources.
Tip 4: Ensure to get enough resources When choosing a topic, make sure it has plenty of resources available. For example, a research paper on xenobiology or cutting-edge nanobiology might sound attractive. Still, you might have difficulties getting data and resources for those unless you are a researcher at a government lab. Data, resources, complex numbers, and statistics are all invaluable to writing a paper about these topics.

That is why we have selected a range of biological topics. The topics on this list are all hopefully exciting topics for research you could write an excellent paper on. We should also add that easy biology topics to research are rare, and a writer usually needs days to prepare and start writing. Yes, biology research topics for high school students are a bit easier, but still, they need time to explore them.

On the other hand, biology research topics for college students are far more complex and detailed. Some people prefer evolutionary biology research paper topics, and we can agree with this claim. These research areas do have a lot of potential and a lot of data to support the claims. Others prefer cell biology research topics that are a bit specific and fun. Anyway, with this article’s list of easy biology research topics, you will surely find the one matching your interest.

For those who may not have the time or resources to do their own research, there are provide assistance with the project.

15 Developmental Biology Topics For Research

Exploring the processes of how cells grow and develop is exciting. The human body contains millions of cells, and it’s interesting to research their behavior under different conditions. If you feel like writing about it, you can find some interesting biology topics below.

How do stem cells form different tissues?
How are tumors formed?
Duplication of genomes
Plasticity of development
Different birth defects
Interactions between genes and the environment
Anticancer drugs mixtures
Developmental diseases: Origin
Drosophila Oogenesis
Most deadly viruses
Most deadly bacteria in the world
How do germs affect cells?
How does leukemia start?
Development of the cardiovascular system in children
How do autoimmune diseases start and affect the human body?

15 Immune System Biology Research Topics

For decades, many scientists and immunologists have studied the human immune system and tried to explain its reaction to various pathogens. This area allows you to deepen into it and reveal how a body protects itself from harmful impact. Look over the biology research questions below and find your match-up.

How does the human body’s immune system work?
The human immune system: How to strengthen it?
What makes the immunological system weaker?
The notion of auto-immune diseases and their effect on the body’s immune system
The global HIV/aids epidemic
What methods are used to prevent the spread of hives?
Living with auto-immune diseases
Genetics and the immune system: effects and consequences
How do immune disorders affect the body, and what causes them?
Are allergies signs of worrying about an immune disorder?
DNA modification in solving immune disorders
Stress as the biggest ruiner of the immunological system
Vaccines as strong supporters of the immunological system
The perception of vaccines in society
Why do some people refuse vaccines and put others around them in danger?

15 Cell Biology Research Topics

Cell study might seem challenging yet very engaging. It will be a good idea to compare various types of cells and compare them in animals and plants. Make your choice from the list of cell biology research topics below.

The structure of an animal cell
Mitochondria and its meaning in cell development
Cells classification and their functions
Red blood cells and their function in transporting oxygen
White blood cells and their responsibility to fight diseases
How are plant cells different from animal cells?
What would it be if animals had a function to photosynthesize?
Single-celled organisms: What is it, and how do they work?
What processes do cells go through in division?
Invasion of bacteria into the body
Viruses – alive or not?
Fungi: their reproduction and distribution
Cancer cells: Why are they so dangerous?
What methods are used to kill cancer cells?
The role of stem cells and their potential in a body

15 DNA Research Topics

The variety of biology research topics for college students might impress you a lot. This is a science with a large field of investigation, disclosing much scientific information to use in your project. The notion of DNA and its gist are also excellent options to write about.

The structure of the human DNA
The main components of a DNA chain
Why does DNA have a double-helix spiral structure?
The purpose of chromosomes
MRNA and its relation to DNA
Do single-celled organisms have DNA?
Do viruses have DNA?
What happens if you have too many or too few chromosomes?
Analyzing the structure of DNA using computers
Uses for the DNA of extinct organisms like mammoths and dinosaurs
Storing non-genetic information in DNA
Can you write a computer program into human DNA?
How does radiation affect DNA?
Modifying DNA to treat aids
Can we fight cancer through DNA modification?

15 Molecular Biology Research Topics

Do you prefer to research molecules’ chemical and physical composition? We gathered some molecular biology research topics to make your choice easier.

The structure and components of a gene
How do molecules move in and out of a cell?
The basic building blocks of life
How are drugs designed for humans?
How is a vaccine designed to target a specific disease?
Dominant genes vs. recessive genes
Prion disease – why is it so dangerous?
Hormones and their function in the body
Developing artificial hormones from other animals
How to carry out a western blot?
Testing and analyzing DNA using PCR
The three-dimensional structure of a molecule
What is DNA transcription, and how is it used?
The structure of a prion
What is the central dogma of molecular biology?

15 Neurobiology Research Topics

The more you dive into science, the more exciting things you find. That’s about biology. Here, you can choose biology research topics for high school and try to reveal more simply.

Nervous system: its structure and function
Neurons as unique cells playing a central role in the nervous system
What is the maximum reaction speed in a human?
Reaction speed: how to improve it?
Research on Organic Farming
What are the symptoms of Alzheimer’s disease?
Why do we feel happy or sad?
Headaches in terms of Neurobiology
What are the reasons for neurobiological degeneration?
Myths and reality of Amnesia
What causes Alzheimer’s Disease, and what are the consequences of the disease?
What is the treatment for Spinal Cord Injury?
Studies on Narcolepsy and Insomnia: What are the causes?
Is there a connection between Mental Health and Neurobiology?
Emotions in terms of their reflection in the brain

15 Abortion, Human cloning, and Genetic Researches Topics

There are so many scientific researches and theories that society accepts or neglects. You can operate different notions and try to explain them, reflecting their advantages and downsides for a human being. We gathered some enticing life science research topics for high school students that might interest you.

The controversy around abortion: legal or not?
Can abortion be safe?
Human cloning – reality vs. science-fiction
The goals of cloning humans
Are human cloning and transplantation ethical?
Having a “perfect child” through gene therapy: Is it a myth?
How far has gene therapy gone in genetic research?
Advantages and disadvantages of gene therapy
How gene therapy can help beat cancer
How gene therapy can eliminate diabetes
The opportunity to edit genes by CRISPR
DNA modifications in humans to enhance our abilities – an ethical dilemma
Will expensive gene therapy widen the gap between the rich and the poor?
Cloning: the good and the Bad for a Generation
The disadvantages of cloning
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15 Environmental and Ecology Topics for Your Research

The nature around us is so enormous and includes many branches to investigate. If you are keen on the environment and how ecology affects it, the list of follow-up biology paper topics might be helpful to you.

The theory of evolution
How does natural selection work?
How do living organisms adapt to their environment?
The concept of divergent and convergent evolution
Building a sustainable environment
Development of environment-friendly cities
How to control population growth?
Why have recycling resources become so essential in the modern world?
The effect of plastic on the environment
What are the global consequences of deforestation?
What can we expect when losing biodiversity?
Ecological damage: How to prevent it?
How can GMO products affect ecology?
Cloning endangered or extinct species: Is it a good idea?
Is climate change the main reason for disrupting ecology?

15 Plant Pathology Biology Research Topics

Many factors impact human health and the quality of food products matters. These easy biology research topics will be useful if you want to describe the connection between those two concepts.

How do plants protect themselves from diseases?
How to increase the plant’s resistance to diseases?
Diseases distribution among plants
The banana pandemic
How do herbicides influence plants?
Corn blight
Can any plant diseases affect humans?
The issue of stem rust and its impact on wheat
What approaches are used to struggle against invasive plants and affected weeds?
Fertilizers: their pros and cons on plants
Plant disease genetics: its system and structure
What is the connection between ecological changes and plant diseases?
Modifications on food production because of plant diseases
How do fungal and viral diseases appear in plants?
The sweet potato virus

15 Animals Biology Research Topics

It’s hard to find someone who doesn’t like animals. If you are curious about animals scientifically, here you are with biology research paper topics in this field.

Classification of animals
Land-based life: its evolution history
Controversies about keeping animals as pets
Is it ethical to test drugs and products on animals?
Why do nature reserves against zoos?
Evidence on prehistoric aquatic animals growing giant
What species of animals are vegan?
Animals and their social behavior
Primate behavior
How intelligent can other primates be?
Are wolves and dogs intelligent?
Domesticating animals
Hibernation in animals
Why animals migrate
Should we bring back extinct animals?

15 Marine Biology Research Topics

The marine theme is engaging as it reveals so many interesting facts about life forms dwelling under the water. You can make your paper look captivating using biology topics in marine below.

How acidification affects aquatic environments
Evolution in the deep sea
What’s the meaning of camouflage mechanism in sea life?
Consequences of oil spills on marine life
Oldest marine species
How do whales communicate with each other?
How blind fish navigate
Are marine shows and aquariums ethical?
The biology and life cycle of seabirds
How jellyfish are immortal
Plankton ecology
Difference between freshwater and seawater marine life
Coral reefs: their importance and evolution
Saving and restoring coral reefs
Life in the deep-sea ocean trenches

15 Zoology Research Topics

Zoology can be an excellent choice to write about if you are close to animal studies. Look at biology topics to research and choose the one that fits your interest most.

Asian elephants and human speech patterns
Oyster genomes and adaptation
Darwin’s work in the Galápagos Islands
Asian carp: Invasive species analysis
Giant squids: Fact vs. fiction
Coyote and wolf hybrid species in the United States
Parasites and disease
Migration patterns of killer bees
The treatment of species in Melville’s Moby Dick
Biodiversity and plankton
The role of camels and the development of Africa and the Middle East
Muskellunge and adaptive creek mechanisms to small water
Ants and cooperative behavior among species
Animal communication and the origin of language
Speech in African Gray Parrots

15 Genetics Research Topics

Writing about modifications caused on the gene level is pretty challenging but very fascinating. You can select one among the biological questions for research and bring up a meaningful paper.

Genetics and its role in cancer studies
Can genetic code be confidential?
Is it possible to choose the sex of a person before birth?
Genetics as a ray of hope for children with an intellectual disability
What factors in human genetics affect behavior?
Is it somehow possible to improve human personality through genetics?
Are there any living cells in the gene?
Fighting HIV with gene mutations
Genetic mutations
How addictive substances affect genes
Genetic testing: is it necessary?
Cloning: positive or negative outcome for future generations
Pros and cons of genetic engineering
Is the world ready for the bioethics revolution?
The linkage between genetics and obesity

15 Biotechnology Research Topics

The way scientists conduct research today is magnificent. Implementing high-tech innovations in biology research brings new opportunities to study the world. What are these opportunities? Explore biotechnology research topics for college students and disclose the best options for you.

Biotechnology used in plant research
What is the contribution of biotechnology to food?
Pharmacogenetics: What is it, and how it works?
How are anti-cancer drugs produced to be effective?
Nanotechnology in DNA: How to isolate it?
Recent nanotechnology used in HIV treatment
What biotech apps are used to detect foodborne pathogens in food systems?
Genotypes research: Why are they tolerant and sensitive to heavy metal?
High-tech solutions in diagnosing cancer
Forensic DNA and its latest developments
Metabolic changes at the level of cells
Nanotechnology in improving treatments for respiratory viruses
The latest biotech discoveries
Digital evolution: bioresearch and its transformation
The concept of vaccine development

15 Evolutionary Biology Research Topics

Knowing how life forms started their existence is fundamental. And more interesting is to look through the evolution of many processes. If you find this trend of research more engaging, we outlined evolutionary biology research paper topics to diversify your choice.

Darwin’s concept’s impact on science
The evolution concept by Lamarck
Origins of the evolutionary theory
Evolution acceptance: a belief vs. a theory?
Evolutionary in microbiology
Development of robotics
Revealing differences: human brain & animal brain
Preservation of biological resources
Transformations in aging
Adaptive genetic system
Morphometrics’ history
Developmental theory and population genomics
Bacteria ecology’s evolution
Biological changes: impact and evolution
Infectious diseases and their profession

The world of science and biology is vast, making research tedious. Use our list of interesting biology research topics to choose the best issue to write your own paper.

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49 Most Interesting Biology Research Topics

August 21, 2023

In need of the perfect biology research topics—ideas that can both showcase your intellect and fuel your academic success? Lost in the boundless landscape of possible biology topics to research? And afraid you’ll never get a chance to begin writing your paper, let alone finish writing? Whether you’re a budding biologist hoping for a challenge or a novice seeking easy biology research topics to wade into, this blog offers curated and comprehensible options.

And if you’re a high school or transfer student looking for opportunities to immerse yourself in biology, consider learning more about research opportunities for high school students , top summer programs for high school students , best colleges for studying biomedical engineering , and best colleges for studying biology .

What is biology?

Well, biology explores the web of life that envelops our planet, from the teeny-tiny microbes to the big complex ecosystems. Biology investigates the molecular processes that define existence, deciphers the interplay of genes, and examines all the dynamic ways organisms interact with their environments. And through biology, you can gain not only knowledge, but a deeper appreciation for the interconnectedness of all living things. Pretty cool!

There are lots and lots of sub-disciplines within biology, branching out in all directions. Throughout this list, we won’t follow all of those branches, but we will follow many. And while none of these branches are truly simple or easy, some might be easier than others. Now we’ll take a look at a few various biology research topics and example questions that could pique your curiosity.

Climate change and ecosystems

The first of our potentially easy biology research topics: climate change and ecosystems. Investigate how ecosystems respond and adapt to the changing climate. And learn about shifts in species distributions , phenology , and ecological interactions .

1) How are different ecosystems responding to temperature changes and altered precipitation patterns?2) What are the implications of shifts in species distributions for ecosystem stability and functioning?

2) Or how does phenology change in response to climate shifts? And how do those changes impact species interactions?

3) Which underlying genetic and physiological mechanisms enable certain species to adapt to changing climate conditions?

4) And how do changing climate conditions affect species’ abilities to interact and form mutualistic relationships within ecosystems?

Microbiome and human health

Intrigued by the relationship between the gut and the rest of the body? Study the complex microbiome . You could learn how gut microbes influence digestion, immunity, and even mental health.

5) How do specific gut microbial communities impact nutrient absorption?

6) What are the connections between the gut microbiome, immune system development, and susceptibility to autoimmune diseases?

7) What ethical considerations need to be addressed when developing personalized microbiome-based therapies? And how can these therapies be safely and equitably integrated into clinical practice?

8) Or how do variations in the gut microbiome contribute to mental health conditions such as anxiety and depression?

9) How do changes in diet and lifestyle affect the composition and function of the gut microbiome? And what are the subsequent health implications?

Urban biodiversity conservation

Next, here’s another one of the potentially easy biology research topics. Examine the challenges and strategies for conserving biodiversity in urban environments. Consider the impact of urbanization on native species and ecosystem services. Then investigate the decline of pollinators and its implications for food security or ecosystem health.

10) How does urbanization influence the abundance and diversity of native plant and animal species in cities?

11) Or what are effective strategies for creating and maintaining green spaces that support urban biodiversity and ecosystem services?

12) How do different urban design and planning approaches impact the distribution of wildlife species and their interactions?

13) What are the best practices for engaging urban communities in biodiversity conservation efforts?

14) And how can urban agriculture and rooftop gardens contribute to urban biodiversity conservation while also addressing food security challenges?

Bioengineering

Are you a problem solver at heart? Then try approaching the intersection of engineering, biology, and medicine. Delve into the field of synthetic biology , where researchers engineer biological systems to create novel organisms with useful applications.

15) How can synthetic biology be harnessed to develop new, sustainable sources of biofuels from engineered microorganisms?

16) And what ethical considerations arise when creating genetically modified organisms for bioremediation purposes?

17) Can synthetic biology techniques be used to design plants that are more efficient at withdrawing carbon dioxide from the atmosphere?

18) How can bioengineering create organisms capable of producing valuable pharmaceutical compounds in a controlled and sustainable manner?

19) But what are the potential risks and benefits of using engineered organisms for large-scale environmental cleanup projects?

Neurobiology

Interested in learning more about what makes creatures tick? Then this might be one of your favorite biology topics to research. Explore the neural mechanisms that underlie complex behaviors in animals and humans. Shed light on topics like decision-making, social interactions, and addiction. And investigate how brain plasticity and neurogenesis help the brain adapt to learning, injury, and aging.

20) How does the brain’s reward circuitry influence decision-making processes in situations involving risk and reward?

21) What neural mechanisms underlie empathy and social interactions in both humans and animals?

22) Or how do changes in neural plasticity contribute to age-related cognitive decline and neurodegenerative diseases?

23) Can insights from neurobiology inform the development of more effective treatments for addiction and substance abuse?

24) What are the neural correlates of learning and memory? And how can our understanding of these processes be applied to educational strategies?

Plant epigenomics

While this might not be one of the easy biology research topics, it will appeal to plant enthusiasts. Explore how epigenetic modifications in plants affect their ability to respond and adapt to changing environmental conditions.

25) How do epigenetic modifications influence the expression of stress-related genes in plants exposed to temperature fluctuations?

26) Or what role do epigenetic changes play in plants’ abilities to acclimate to changing levels of air pollution?

27) Can certain epigenetic modifications be used as indicators of a plant’s adaptability to new environments?

28) How do epigenetic modifications contribute to the transgenerational inheritance of traits related to stress resistance?

29) And can targeted manipulation of epigenetic marks enhance crop plants’ ability to withstand changing environmental conditions?

Conservation genomics

Motivated to save the planet? Conservation genomics stands at the forefront of modern biology, merging the power of genetics with the urgent need to protect Earth’s biodiversity. Study genetic diversity, population dynamics, and how endangered species adapt in response to environmental changes.

30) How does genetic diversity within endangered species influence their ability to adapt to changing environmental conditions?

31) What genetic factors contribute to the susceptibility of certain populations to diseases, and how can this knowledge inform conservation strategies?

32) How can genomic data be used to inform captive breeding and reintroduction programs for endangered species?

33) And what are the genomic signatures of adaptation in response to human-induced environmental changes, such as habitat fragmentation and pollution?

34) Or how can genomics help identify “hotspots” of biodiversity that are particularly important for conservation efforts?

Zoonotic disease transmission

And here’s one of the biology research topics that’s been on all our minds in recent years. Investigate the factors contributing to the transmission of zoonotic diseases , like COVID-19. Then posit strategies for prevention and early detection.

35) What are the ecological and genetic factors that facilitate the spillover of zoonotic pathogens from animals to humans?

36) Or how do changes in land use, deforestation, and urbanization impact the risk of zoonotic disease emergence?

37) Can early detection and surveillance systems be developed to predict and mitigate the spread of zoonotic diseases?

38) How do social and cultural factors influence human behaviors that contribute to zoonotic disease transmission?

39) And can strategies be implemented to improve global pandemic preparedness?

Bioinformatics

Are you a data fanatic? Bioinformatics involves developing computational tools and techniques to analyze and interpret large biological datasets. This enables advancements in genomics, proteomics, and systems biology. So delve into the world of bioinformatics to learn how large-scale genomic and molecular data are revolutionizing biological research.

40) How can machine learning algorithms predict the function of genes based on their DNA sequences?

41) And what computational methods can identify potential drug targets by analyzing protein-protein interactions in large biological datasets?

42) Can bioinformatics tools be used to identify potential disease-causing mutations in human genomes and guide personalized medicine approaches?

43) What are the challenges and opportunities in analyzing “omics” data (genomics, proteomics, transcriptomics) to uncover novel biological insights?

44) Or how can bioinformatics contribute to our understanding of microbial diversity, evolution, and interactions within ecosystems?

Regenerative medicine

While definitely not one of the easy biology research topics, regenerative medicine will appeal to those interested in healthcare. Research innovative approaches to stimulate tissue and organ regeneration, using stem cells, tissue engineering, and biotechnology. And while you’re at it, discover the next potential medical breakthrough.

45) How can stem cells be directed to differentiate into specific cell types for tissue regeneration, and what factors influence this process?

46) Or what are the potential applications of 3D bioprinting in creating functional tissues and organs for transplantation?

47) How can bioengineered scaffolds enhance tissue regeneration and integration with host tissues?

48) What are the ethical considerations surrounding the use of stem cells and regenerative therapies in medical treatments?

49) And can regenerative medicine approaches be used to treat neurodegenerative disorders and restore brain function?

Biology Research Topics – Final thoughts

So as you take your next steps, try not to feel overwhelmed. And instead, appreciate the vast realm of possibilities that biology research topics offer. Because the array of biology topics to research is as diverse as the ecosystems it seeks to understand. And no matter if you’re only looking for easy biology research topics, or you’re itching to unravel the mysteries of plant-microbe interactions, your exploration will continue to deepen what we know of the world around us.

High School Success

Mariya holds a BFA in Creative Writing from the Pratt Institute and is currently pursuing an MFA in writing at the University of California Davis. Mariya serves as a teaching assistant in the English department at UC Davis. She previously served as an associate editor at Carve Magazine for two years, where she managed 60 fiction writers. She is the winner of the 2015 Stony Brook Fiction Prize, and her short stories have been published in Mid-American Review , Cutbank , Sonora Review , New Orleans Review , and The Collagist , among other magazines.

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200+ Unique And Interesting Biology Research Topics For Students In 2023

Are you curious about the fascinating world of biology and its many research possibilities? Well, you are in the right place! In this blog, we will explore biology research topics, exploring what biology is, what constitutes a good research topic, and how to go about selecting the perfect one for your academic journey.

So, what exactly is biology? Biology is the study of living organisms and their interactions with the environment. It includes everything from the tiniest cells to the largest ecosystems, making it a diverse and exciting field of study.

Stay tuned to learn more about biology research topics as we present over 200 intriguing research ideas for students, emphasizing the importance of selecting the right one. In addition, we will also share resources to make your quest for the perfect topic a breeze. Let’s embark on this scientific journey together!

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What Is Biology?

Table of Contents

Biology is the study of living things, like animals, plants, and even tiny organisms too small to see. It helps us understand how these living things work and how they interact with each other and their environment. Biologists, or scientists who study biology, explore topics like how animals breathe, how plants grow, and how our bodies function. By learning about biology, we can better care for the Earth and all its living creatures.

What Is A Good Biology Research Topic?

A good biology research topic is a question or problem in the field of biology that scientists want to investigate and learn more about. It should be interesting and important, like studying how a new medicine can treat a disease or how animals adapt to changing environments. The topic should also be specific and clear, so researchers can focus on finding answers. Additionally, it’s helpful if the topic hasn’t been studied extensively before, so the research can contribute new knowledge to the field of biology and help us better understand the natural world.

Tips For Choosing A Biology Research Topics

Here are some tips for choosing a biology research topics:

1. Choose What Interests You

When picking a biology research topic, go for something that you personally find fascinating and enjoyable. When you’re genuinely curious about it, you’ll be more motivated to study and learn.

2. Select a Significant Topic

Look for a subject in biology that has real-world importance. Think about whether your research can address practical issues, like finding cures for diseases or understanding environmental problems. Research that can make a positive impact is usually a good choice.

3. Check If It’s Doable

Consider if you have the necessary tools and time to carry out your research. It’s essential to pick a topic that you can actually study with the resources available to you.

4. Add Your Unique Perspective

Try to find a fresh or different angle for your research. While you can build upon existing knowledge, bringing something new or unique to the table can make your research more exciting and valuable.

5. Seek Guidance

Don’t hesitate to ask for advice from your teachers or experienced researchers. They can provide you with valuable insights and help you make a smart decision when choosing your research topic in biology.

Biology Research Topics For College Students

1. Investigating the role of genetic mutations in cancer development.

2. Analyzing the impact of climate changes on wildlife populations.

3. Studying the ecology of invasive species in urban environments.

4. Investigating the microbiome of the human gut and its relationship to health.

5. Analyzing the genetic diversity of endangered species for conservation.

6. Studying the evolution of antibiotic resistance in bacteria.

7. Investigating the ecological consequences of deforestation.

8. Analyzing the behavior and communication of social insects like ants and bees.

9. Studying the physiology of extreme environments, such as deep-sea hydrothermal vents.

10. Investigating the molecular mechanisms of cell division and mitosis.

Plant Biology Research Topics For College Students

11. Studying the impact of different fertilizers on crop yields and soil health.

12. Analyzing the genetics of plant resistance to pests and diseases.

13. Investigating the role of plant hormones in growth and development.

14. Studying the adaptation of plants to drought conditions.

15. Analyzing the ecological interactions between plants and pollinators.

16. Investigating the use of biotechnology to enhance crop traits.

17. Studying the genetics of plant breeding for improved varieties.

18. Analyzing the physiology of photosynthesis and carbon fixation in plants.

19. Investigating the effects of soil microbiota on plant health.

20. Studying the evolution of plant species in response to changing environments.

Biotechnology Research Topics For College Students

21. Investigating the use of CRISPR-Cas9 technology for genome editing.

22. Analyzing the production of biofuels from microorganisms.

23. Studying the application of biotechnology in medicine, such as gene therapy.

24. Investigating the use of bioplastics as a sustainable alternative to conventional plastics.

25. Analyzing the role of biotechnology in food production, including GMOs.

26. Studying the development of biopharmaceuticals and monoclonal antibodies.

27. Investigating the use of bioremediation to clean up polluted environments.

28. Studying the potential of synthetic biology for creating novel organisms.

29. Analyzing the ethical and social implications of biotechnological advancements.

30. Investigating the use of biotechnology in forensic science, such as DNA analysis.

Molecular Biology Research Topics For Undergraduates

31. Studying the structure and function of DNA and RNA molecules.

32. Analyzing the regulation of gene expression in eukaryotic cells.

33. Investigating the mechanisms of DNA replication and repair.

34. Studying the role of non-coding RNAs in gene regulation.

35. Analyzing the molecular basis of genetic diseases like cystic fibrosis.

36. Investigating the epigenetic modifications that control gene activity.

37. Studying the molecular mechanisms of protein folding and misfolding.

38. Analyzing the molecular pathways involved in cancer progression.

39. Investigating the molecular basis of neurodegenerative diseases.

40. Studying the use of molecular markers in genetic diversity analysis.

Life Science Research Topics For High School Students

41. Investigating the effects of different diets on human health.

42. Analyzing the impact of exercise on cardiovascular fitness.

43. Studying the genetics of inherited traits and diseases.

44. Investigating the ecological interactions in a local ecosystem.

45. Analyzing the diversity of microorganisms in soil or water samples.

46. Studying the anatomy and physiology of a specific organ or system.

47. Investigating the life cycle of a local plant or animal species.

48. Studying the effects of environmental pollutants on aquatic organisms.

49. Analyzing the behavior of a specific animal species in its habitat.

50. Investigating the process of photosynthesis in plants.

Biology Research Topics For Grade 12

51. Investigating the genetic basis of a specific inherited disorder.

52. Analyzing the impact of climate change on a local ecosystem.

53.Studying the biodiversity of a particular rainforest region.

54. Investigating the physiological adaptations of animals to extreme temperatures.

55. Analyzing the effects of pollution on aquatic ecosystems.

56. Studying the life history and conservation status of an endangered species.

57. Investigating the molecular mechanisms of a specific disease.

58. Studying the ecological interactions within a coral reef ecosystem.

59. Analyzing the genetics of plant hybridization and speciation.

60. Investigating the behavior and communication of a particular bird species.

Marine Biology Research Topics

61. Studying the impact of ocean acidification on coral reefs.

62. Analyzing the migration patterns of marine mammals.

63. Investigating the physiology of deep-sea creatures under high pressure.

64. Studying the ecology of phytoplankton and their role in the marine food web.

65. Analyzing the behavior of different species of sharks.

66. Investigating the conservation of sea turtle populations.

67. Studying the biodiversity of deep-sea hydrothermal vent communities.

68. Analyzing the effects of overfishing on marine ecosystems.

69. Investigating the adaptation of marine organisms to extreme cold in polar regions.

70. Studying the bioluminescence and communication in marine organisms.

AP Biology Research Topics

71. Investigating the role of specific enzymes in cellular metabolism.

72. Analyzing the genetic variation within a population.

73. Studying the mechanisms of hormonal regulation in animals.

74. Investigating the principles of Mendelian genetics through trait analysis.

75. Analyzing the ecological succession in a local ecosystem.

76. Studying the physiology of the human circulatory system.

77. Investigating the molecular biology of a specific virus.

78. Studying the principles of natural selection through evolutionary simulations.

79. Analyzing the genetic diversity of a plant species in different habitats.

80. Investigating the effects of different environmental factors on plant growth.

Cell Biology Research Topics

81. Investigating the role of mitochondria in cellular energy production.

82. Analyzing the mechanisms of cell division and mitosis.

83. Studying the function of cell membrane proteins in signal transduction.

84. Investigating the cellular processes involved in apoptosis (cell death).

85. Analyzing the role of endoplasmic reticulum in protein synthesis and folding.

86. Studying the dynamics of the cytoskeleton and cell motility.

87. Investigating the regulation of cell cycle checkpoints.

88. Analyzing the structure and function of cellular organelles.

89. Studying the molecular mechanisms of DNA replication and repair.

90. Investigating the impact of cellular stress on cell health and function.

Human Biology Research Topics

91. Analyzing the genetic basis of inherited diseases in humans.

92. Investigating the physiological responses to exercise and physical activity.

93. Studying the hormonal regulation of the human reproductive system.

94. Analyzing the impact of nutrition on human health and metabolism.

95. Investigating the role of the immune system in disease prevention.

96. Studying the genetics of human evolution and migration.

97. Analyzing the neural mechanisms underlying human cognition and behavior.

98. Investigating the molecular basis of aging and age-related diseases.

99. Studying the impact of environmental toxins on human health.

100. Analyzing the genetics of organ transplantation and tissue compatibility.

Molecular Biology Research Topics

101. Investigating the role of microRNAs in gene regulation.

102. Analyzing the molecular basis of genetic disorders like cystic fibrosis.

103. Studying the epigenetic modifications that control gene expression.

104. Investigating the molecular mechanisms of RNA splicing.

105. Analyzing the role of telomeres in cellular aging.

106. Studying the molecular pathways involved in cancer metastasis.

107. Investigating the molecular basis of neurodegenerative diseases.

108. Studying the molecular interactions in protein-protein networks.

109. Analyzing the molecular mechanisms of DNA damage and repair.

110. Investigating the use of CRISPR-Cas9 for genome editing.

Animal Biology Research Topics

111. Studying the behavior and communication of social insects like ants.

112. Analyzing the physiology of hibernation in mammals.

113. Investigating the ecological interactions in a predator-prey relationship.

114. Studying the adaptations of animals to extreme environments.

115. Analyzing the genetics of inherited traits in animal populations.

116. Investigating the impact of climate change on animal migration patterns.

117. Studying the diversity of marine life in coral reef ecosystems.

118. Analyzing the physiology of flight in birds and bats.

119. Investigating the molecular basis of animal coloration and camouflage.

120. Studying the behavior and conservation of endangered species.

Neuroscience Research Topics
Mental Health Research Topics

Plant Biology Research Topics

121. Investigating the role of plant hormones in growth and development.

122. Analyzing the genetics of plant resistance to pests and diseases.

123. Climate change and plant phenology are being examined.

124. Investigating the ecology of mycorrhizal fungi and their symbiosis with plants.

125. Investigating plant photosynthesis and carbon fixing.

126. Molecular analysis of plant stress responses.

127. Investigating the adaptation of plants to drought conditions.

128. Studying the role of plants in phytoremediation of polluted environments.

129. Analyzing the genetics of plant hybridization and speciation.

130. Investigating the molecular basis of plant-microbe interactions.

Environmental Biology Research Topics

131. Analyzing the effects of pollution on aquatic ecosystems.

132. Investigating the biodiversity of a particular ecosystem.

133. Studying the ecological consequences of deforestation.

134. Analyzing the impact of climate change on wildlife populations.

135. Investigating the use of bioremediation to clean up polluted sites.

136. Studying the environmental factors influencing species distribution.

137. Analyzing the effects of habitat fragmentation on wildlife.

138. Investigating the ecology of invasive species in new environments.

139. Studying the conservation of endangered species and habitats.

140. Analyzing the interactions between humans and urban ecosystems.

Chemical Biology Research Topics

141. Investigating the design and synthesis of new drug compounds.

142. Analyzing the molecular mechanisms of enzyme catalysis.

143.Studying the role of small molecules in cellular signaling pathways.

144. Investigating the development of chemical probes for biological research.

145. Studying the chemistry of protein-ligand interactions.

146. Analyzing the use of chemical biology in cancer therapy.

147. Investigating the synthesis of bioactive natural products.

148. Studying the role of chemical compounds in microbial interactions.

149. Analyzing the chemistry of DNA-protein interactions.

150. Investigating the chemical basis of drug resistance in pathogens.

Medical Biology Research Topics

151. Investigating the genetic basis of specific diseases like diabetes.

152. Analyzing the mechanisms of drug resistance in bacteria.

153. Studying the molecular mechanisms of autoimmune diseases.

154. Investigating the development of personalized medicine approaches.

155. Studying the role of inflammation in chronic diseases.

156. Analyzing the genetics of rare diseases and genetic syndromes.

157. Investigating the molecular basis of viral infections and vaccines.

158. Studying the mechanisms of organ transplantation and rejection.

159. Analyzing the molecular diagnostics of cancer.

160. Investigating the biology of stem cells and regenerative medicine.

Evolutionary Biology Research Topics

161. Studying the evolution of human ancestors and early hominids.

162. The genetic variety of species and between species is being looked at.

163. Investigating the role of sexual selection in animal evolution.

164. Studying the co-evolutionary relationships between parasites and hosts.

165. Analyzing the evolutionary adaptations of extremophiles.

166. Investigating the evolution of developmental processes (evo-devo).

167. Studying the biogeography and distribution of species.

168. Analyzing the evolution of mimicry in animals and plants.

169. Investigating the genetics of speciation and hybridization.

170. Studying the evolutionary history of domesticated plants and animals.

Cellular Biology Research Topics

171. Investigating the role of autophagy in cellular homeostasis.

172. Analyzing the mechanisms of cellular transport and trafficking.

173. Studying the regulation of cell adhesion & migration.

174. Investigating the cellular responses to DNA damage.

175. Analyzing the dynamics of cellular membrane structures.

176. Studying the role of cellular organelles in lipid metabolism.

177. Investigating the molecular mechanisms of cell-cell communication.

178. Studying the physiology of cellular respiration and energy production.

179. Analyzing the cellular mechanisms of viral entry and replication.

180. Investigating the role of cellular senescence in aging and disease.

Good Biology Research Topics Related To Brain Injuries

181. Analyzing the molecular mechanisms of traumatic brain injury.

182. Investigating the role of neuroinflammation in brain injury recovery.

183. Studying the impact of concussions on long-term brain health.

184. Analyzing the use of neuroimaging in diagnosing brain injuries.

185. Investigating the development of neuroprotective therapies.

186. Studying the genetics of susceptibility to brain injuries.

187. Analyzing the cognitive and behavioral effects of brain trauma.

188. Investigating the role of rehabilitation in brain injury recovery.

189. Studying the cellular and molecular changes in axonal injury.

190. Looking into how stem cell therapy might be used to help brain injuries.

Biology Quantitative Research Topics

191. Investigating the mathematical modeling of population dynamics.

192. Analyzing the statistical methods for biodiversity assessment.

193. Studying the use of bioinformatics in genomics research.

194. Investigating the quantitative analysis of gene expression data.

195. Studying the mathematical modeling of enzyme kinetics.

196. Analyzing the statistical approaches for epidemiological studies.

197. Investigating the use of computational tools in phylogenetics.

198. Studying the mathematical modeling of ecological systems.

199. Analyzing the quantitative analysis of protein-protein interactions.

200. Investigating the statistical methods for analyzing genetic variation.

Importance Of Choosing The Right Biology Research Topics

Here are some importance of choosing the right biology research topics:

1. Relevance to Your Interests and Goals

Choosing the right biology research topic is important because it should align with your interests and goals. Studying something you’re passionate about keeps you motivated and dedicated to your research.

2. Contribution to Scientific Knowledge

Your research should contribute something valuable to the world of science. Picking the right topic means you have the chance to discover something new or solve a problem, advancing our understanding of the natural world.

3. Availability of Resources

Consider the resources you have or can access. If you pick a topic that demands resources you don’t have, your research may hit a dead end. Choosing wisely means you can work efficiently.

4. Feasibility and Manageability

A good research topic should be manageable within your time frame and capabilities. If it’s too broad or complex, you might get overwhelmed. Picking the right topic ensures your research is doable.

5. Real-World Impact

Think about how your research might benefit the real world. Biology often has implications for health, the environment, or society. Choosing a topic with practical applications can make your work meaningful and potentially change lives.

Resources For Finding Biology Research Topics

There are numerous resources for finding biology research topics:

1. Online Databases

Look on websites like PubMed and Google Scholar. They have lots of biology articles. Type words about what you like to find topics.

2. Academic Journals

Check biology magazines. They talk about new research. You can find ideas and see what’s important.

3. University Websites

Colleges show what their teachers study. Find teachers who like what you like. Ask them about ideas for your own study.

4. Science News and Magazines

Read science news. They tell you about new things in biology. It helps you think of research ideas.

5. Join Biology Forums and Communities

Talk to other people who like biology online. You can ask for ideas and find friends to help you. Use websites like ResearchGate and Reddit for this.

Conclusion

Biology Research Topics offer exciting opportunities for exploration and learning. We’ve explained what biology is and stressed the importance of picking a good research topic. Our tips and extensive list of over 200 biology research topics provide valuable guidance for students.

Selecting the right topic is more than just getting good grades; it’s about making meaningful contributions to our understanding of life. We’ve also shared resources to help you discover even more topics. So, embrace the world of biology research, embark on a journey of discovery, and be part of the ongoing effort to unravel the mysteries of the natural world.

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212 Unique Biology Research Topics For Students And Researchers

Every student studying something related to biology — botany, marine, animal, medicine, molecular or physical biology, is in an interesting field. It’s a subject that explores how animate and inanimate objects relate to themselves. The field unveils the past, the present, and what lies in the future of the relationship between the living and nonliving things.

This is precisely why you need custom and quality biology topics for your college and university essay or project. It’ll make it easy to brainstorm, research, and get to writing straight away. Before the deep dive, what is biology?

What Is Biology?

Everyone knows it’s the scientific study of life, but beyond that, biology facilitates the comprehension of living and nonliving things. It’s a branch that explores their anatomy, behavior, distribution, morphology, and physiology.

For example, it understands how genes are classified and constituted into generations. It encompasses various branches, including botany, medicine, genetics, ecology, marine biology, zoology, and molecular biology.

Here are what some of these mean:

Botany: This study of plants examines their structure, physiology, ecology, economic importance, and distribution, among others. It also deals with their biochemical processes, properties, and social interactions between plants. It extends to how plants are vital for human life, survival, and growth and how they play a significant role in stabilizing environmental health. Zoology: Zoology studies animal behavior, brain, structure, physiology, class, and distribution. It’s the general study of the lives of both living and extinct animals. It explains animal classification, the animal kingdom, evolution, habitat, embryology, and life span. Physiology: Physiology deals with the daily functions of the human body: How it works and the factors that make it work. It examines molecular behavior, the chemistry and physics behind locomotion, and how the cells in the living organisms’ body function. It helps understand how humans and animals get sick and what can be done to alleviate pain. Microbiology: Dealing with microorganisms, it examined how viruses, algae, fungi, bacteria, protozoa, and slime molds become parts of human life. They’re regarded as microbes, which play substantial roles in the human biochemical processes, including climate change, biodegradation, biodeterioration, food spoilage, biotech, and epidemiology. Marine Biology: This is the scientific study of organs in the sea. It understands their family classification, how they survive, and what makes wild marine animals different from domesticated and consumable ones. It also explores their interaction with the environment through several processes. The marine biologist studies marines in their natural environment, collects data on their characteristics, human impact on their living, and how they relate with themselves.

Now that you know all these, here are some custom biology topics to research for your university or college essay and paper.

Controversial Biology Topics

There are many controversial subjects in every field, and biology isn’t exempt from controversy. If you’d like to create an original essay through diverse opinions, here are biology topics for you:

What are your thoughts on the post-Roe V Wade world?
How can the post-Roe V Wade policy affect developing countries looking up to America for their laws?
Abortion and feminism: discuss
Does saving life justify cloning?
Explain the principle of abortion in medical practice
The effects of cloning in medicine
How does genetics contribute to obesity?
Explain why a parent could have Hepatitis B virus and only one of five offspring have the virus
Is homosexuality really in the gene?
How does depression correlate with genetics?
Additives and how they affect the genes
Examine how genetic mutations work
Discuss the grounds that you could prove for legalizing human cloning
Which is more immoral: Human or animal cloning?
How is nanotechnology different from biotechnology?
Discuss the manifestation of nanotechnology in science
Explain three instances where public opinion has held back scientific inventions
How does transgenic crop work?
Would you say genetically modified food is safe for consumption?
Explain why sexual abuse leads to trauma.

Biology Research Paper Topics

You’d need to write an extensive paper on biology one day. This could be when you’re in your final year in college or the university or submitting to a competition. You’d need Biology topics to research for brainstorming, and here are 30 of them:

Stem cells and tissue formation processes
Why are there different congenital disabilities?
Mixtures in anticancer drugs?
What are the complexities of existing HIV drugs?
What is the contribution of chemotherapy to cancer?
Examine the chemotherapy process and why it doesn’t work for some patients.
Explain the origin of developmental diseases
How do germs affect the cells?
What are the consequences of the sun on the white person’s and black person’s skin?
Why are some diseases treatable through drugs while some are not?
Scientific lessons learned from COVID-19 and ideas to tackle the next virus
If animals are carriers of the virus, what should be done to them?
Examine five animals in extinction and what led to it
Discuss the subject of endangered species and why people should care
Is a plant-based diet sustainable for human health?
Account for the consequence of living on Mars on human health
Discuss the inconveniences involved in space travel
How does space flight contribute to environmental disasters
Discuss the emergence of leukemia
Explain how the immune systems in humans work
Evaluate the factors that weaken the immunological system
What would you consider the deadliest virus?
Autoimmune: what is it, origin and consequences
Immune disorder: origin and how it affects the body
Does stress affect the ability to have sex?
Contribution of vaccine to eradicating disease: Discuss
What are the complexities in taking the Hepatitis B vaccine while being positive?
Allergies: why do humans have them?
DNA modification: how does it work?
Explain the misconceptions about the COVID-19 vaccines.

Interesting Biology Topics

Biology doesn’t have to be boring. Different aspects of biology could be fun to explore, especially if you’ve had a flair for the study since your elementary school classes.

You can either write an essay or paper with the following interesting biology research topics:

Human emotions and conflicts with their intellectual intelligence
Emotions: Its influence on art and music and how the perception of art influences the world
The consequences of marijuana and alcohol on teenagers
Compare and contrast how alcohol affects teenagers and adults
Discuss the contributions of neuroscience to the subject of emotional pain
Explain how the brain process speech
Discuss the factors that cause autism
Explain what is meant when people say humans are animals
Why do scientists say humans are pessimists?
Factors contributing to the dopamine levels human experience
How does isolation affect the human brain?
What factors contribute to instinctive responses?
Noise pollution: how it affects living organisms
Fire ecology: The contributions of plants to fire outbreak
Explain the science behind how hot temperature, soil, and dry grass start a fire
Microbes: what do you understand by bioremediation?
Explain urban ecology and the challenges it pokes to solve
Discuss how excessive internet usage affects the human memory
Evaluate how conservation biology contributes to the extinction prevention efforts
Discuss the role of satellites and drones in understanding the natural world
Why do we need space travel and studies?
Explain the limitations of limnology studies
What are infectious-disease-causing agents all about?
Discuss what epigenetics studies encompass
Why is cancer research essential to the world?
Discuss climate change: Governments are not interested, and there is no alternative
How is behavioral science studies a core part of the understanding of the world?
Discuss the issues with genetic engineering and why it’s a challenge
Evaluate the strengths and weaknesses in the arguments for a plant-based diet
Create a survey amongst students of biology asking why they chose to study the course.

Biology Research Topics For College Students

If you find any of the above beyond your intellectual and Research capacity, here are some topics you can handle. You can use these for your essays, projects, quizzes, or competitions.

These custom yet popular biology research topics will examine famous personalities and other discourse in biology:

Effects of the human hormone on the mind
Why do men get erect even when they’re absentminded?
How does women’s arousal work?
How can melatonin be valuable for therapy?
Risky behavior: Hormones responsible for the risk
Stem and cloning: what is the latest research on the subject?
Hormones: changes in pregnancy
Why do pregnant women have an appetite for random and remote things?
The role of physical activities in hormone development
Examine the benefits and threats of transgenic crops
The fight against COVID-19: assess current successes
The fight against smallpox: assess current successes
The fight against HIV: history, trends, and present research
Discuss the future of prosthetic appliances
Examine the research and the future of mind-controlled limbs
What does cosmetic surgery mean, and why is it needed?
Analyze the meaning and process of vascular surgery
Discuss the debate around changes in genital organs for males and females in transgender bodies
How do donors and organ transplants work?
Account for the work of Dr. Malcom E Miller
Discuss the contribution of Charles Darwin to human evolution
Explain the trends in biomedicine
Discuss the functions of x-rays in botany
Assess the most efficient systems for wildlife preservation
Examine how poverty contributes to climate hazards
Discuss the process involved in plant metabolism
The transformation of energy into a living thing: discuss
Prevention for sexually transmitted disease: What are the misconceptions?
Analyze how the human body reacts to poison
Russian Poisoning: What are the lessons scientists must learn?
COVID-19: Discuss the efforts by two or three governments to prevent the spread
Discuss the contributions of Pfizer during the pandemic.

Marine Biology Research Topics

This subject explains orgasms in the sea, how they survive, and their interaction with their environment. If you have a flair for this field, the following Biology research topics may interest you:

Discuss what quantitative ecology through modeling means
Smallest diatoms and marine logistics: discuss
How is the shark studied?
Acidification of seas: Causes and consequences
Discuss the concept of the immortality of Jellyfishes
Discuss the differences between seawater and freshwater in marine study
Account for some of the oldest marine species
Discuss the evolution of the deep sea
Explain whales’ communication techniques
What does plankton ecology encompass?
The importance of coral reefs to seawater
Challenges that encompass geological oceanography
How tourism affects natural animal habitat
Discuss some instances of the domestication of wild marine animals
Coastal zone: pros and cons of living in such areas
How do sharks perceive enemies?
Analyze why some animals can live in water but can’t live on land
Explain how plants survive in the sea
Compare and contrast the different two species of animals in the water
How can marine energy be generated, stored, and used?

Molecular Biology Research Topics

Focusing on the construct of cells and analysis of their composition, it understands the alteration and maintenance of cellular processes. If you’d like to focus on molecular biology, here are 15 good biology research topics for you:

Ethical considerations in molecular genetics
Discuss the structure and component of the gene
Examine the restrictions in DNA
What are the peculiarities in modern nucleic acid analysis
What goes into the Pharmaceutical production of drugs
Evaluate the building blocks of life
Discuss the systems of RNA translation to protein
PCR: How DNA is tested and analyzed
Why is prion disease so dangerous?
Compare and contrast recessive genes vs. dominant genes
Can there be damage to the human DNA, and can it be repaired?
Constraints in the research of microarray data analysis
Protein purification: How it evolves
Objectives of nucleic acid
Explain the structure of a prion.

Biology Research Topics For High School

Your teachers and professors will be awed if you create impeccable essays for your next report. You need to secure the best grades as you move closer to graduation, and brainstorming any of these popular biology research topics will help:

Identify the most endangered species
The challenges to animal extinction
What are the things everyone should know about sea life?
Discuss the history of genetics
Explain the biological theory of Charles Darwin
How did the lockdown affect social interaction?
Why do some people refuse the vaccine?
Origin of genetics
What is animal hunting, and why is it fashionable
Explain the evolution of a virus
Role of lockdown in preventing deaths and illnesses
Invasive species: What does it mean?
Endangered animals: How do they survive in the face of their hazards?
Lockdown and their role in reducing coronavirus transmission
Vaccine distribution: Ideas for global distribution
Why can viruses become less virulent?
Discuss the evolution of the world
Explain the evolution of the planet
Explain what Elon Musk means when he says life on Mars is possible
What does herd immunity mean?
Flu: why is there a low incidence in 2020?
Relationship between archaeology and biology
Antiviral drug: What it means
Factors leading to the evolution of humans
Give instances of what natural selection means
What is considered the dead branches of evolution
Whale hunting: What it means and the present trends
Who is Stephen Jay, and what is his role in paleontology?
Origin of diseases: why must humans fall sick?
Why are humans called higher animals?

Human Biology Research Topics

Human biology understands humans and their relationship between themselves and their environment. It also studies how the body works and the impediments to health. Here are some easy biology research topics to explore on the subject:

How do gut bacteria affect the brain?
What are the ethical concerns around organ transplants?
The consequence of alcohol on the liver
The consequences of extreme salt on the human body
Why do humans need to deworm regularly?
The relationship between obesity and genetics
Genetically modified foods: Why are they needed?
How sun exposure affects human skin
Latest trends: Depression is hereditary
Influence of music on the human brain
What are the stages of lung cancer
Forensic DNA: latest trends
How visual consumptions affect how humans think
What is the process that leads to pregnancy?
Explain the role of nanotechnology in HIV research
Discuss any experiment with stem cells you know about
Explain how humans consume food
Discuss the process of metabolism as well as its criticality to human health
Explore the consistent challenges technology poses to human health
Explain the process of body decay to a skeleton.

Cell Biology Research Topics

There are many evolutionary biology research paper topics formed not by the nomenclature but for what they stand for. Cell biology is one of the most complex branches of the field.

It examines minor units and the living organisms that make them up. The focus is on the relationship between the cytoplasm, membrane, and parts of the cell. Here are some topics to explore for your scientific dissertation writing :

How does chromatin engage in the alterations of gene expression?
What are the usual cell infections, and why does the body have immunity defections?
Identify and account for the heritage of Robert Brown in his core career focus
Explain the structure of the animal cell and why It’s what it is
Identify the cells in the human body as well as their functions
Explain a scenario and justify the context of animals photosynthesizing like plants
Why do bacteria invade the body, and how do they do it?
Why are mitochondria considered the powerhouse of the cell
Use the molecular analysis tool to explain multicellular organisms
Examine how the White blood cells fight disease
What do you understand about the role of cell biology in the treatment of Alzheimer’s Disease
What are the latest research methods in cell biology?
Identify the characteristics of viruses and why they threaten human existence.
Discuss the differences between DNA and RNA
What part of the body is responsible for human functionality for as long as the individual wants?

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350+ Biology Research Topics

Biology is a vast field of study that explores the diverse aspects of life, from the smallest organisms to the complex ecosystems they inhabit. With new discoveries being made every day, the field of biology is constantly evolving and expanding. As a result, there are numerous research topics within biology that can capture the imagination of students, researchers , and professionals alike. Whether you’re interested in genetics, ecology, microbiology, or any other subfield of biology, there is no shortage of fascinating topics to explore. In this post, we will discuss some of the most compelling biology research topics that you can delve into.

Biology Research Topics

Biology Research Topics are as follows:

The role of gut microbiota in human health and disease.
The effects of climate change on animal behavior and physiology.
The molecular mechanisms of cancer development and progression.
The evolutionary origins of human language.
The impact of pesticides on insect populations and ecosystems.
The genetic basis of aging and longevity.
The ecological importance of microbial communities in soil.
The physiology and behavior of marine mammals.
The molecular mechanisms of viral infections.
The evolutionary history of flowering plants.
The ecological impacts of invasive species.
The role of epigenetics in gene regulation and disease.
The evolution of social behavior in animals.
The physiology and ecology of birdsong.
The impact of antibiotics on gut microbiota and human health.
The role of the microbiome in psychiatric disorders.
The evolutionary history of human migrations.
The ecological and physiological effects of light pollution on animals.
The mechanisms of cell division and differentiation.
The ecological impacts of deforestation.
The molecular mechanisms of drug addiction.
The genetic basis of plant resistance to pests and diseases.
The evolutionary history of human diet and nutrition.
The molecular mechanisms of neurodegenerative diseases.
The ecology and evolution of sexual selection.
The physiological and behavioral effects of air pollution on animals.
The role of epigenetics in plant development and stress response.
The evolutionary history of animal domestication.
The molecular mechanisms of genetic diseases.
The ecological impacts of climate change on plants.
The evolutionary history of human mating systems.
The physiological and behavioral effects of noise pollution on animals.
The genetic basis of intelligence and cognitive abilities.
The ecological and physiological effects of ocean acidification on marine organisms.
The molecular mechanisms of immune system function and dysfunction.
The evolutionary history of human social structures.
The ecological impacts of plastic pollution on marine ecosystems.
The genetic basis of animal migration.
The physiological and behavioral effects of light and dark cycles on animals.
The ecological and evolutionary dynamics of symbiosis.
The molecular mechanisms of gene regulation and expression.
The evolutionary history of human disease resistance.
The ecological impacts of overfishing on marine ecosystems.
The genetic basis of animal communication.
The physiological and behavioral effects of temperature changes on animals.
The ecological and evolutionary dynamics of parasitism.
The molecular mechanisms of circadian rhythms.
The evolutionary history of human social cognition.
The ecological impacts of urbanization on wildlife.
The genetic basis of antibiotic resistance in bacteria.
The impact of climate change on insect population dynamics.
The role of the microbiome in the development of autoimmune diseases.
The genetic basis of complex human diseases such as diabetes and heart disease.
The evolution of plant secondary metabolites and their ecological functions.
The effects of anthropogenic noise on animal communication and behavior.
The molecular mechanisms of protein synthesis and folding.
The role of RNA in gene expression and regulation.
The ecology and evolution of microbial symbioses in plants.
The physiological and behavioral effects of air temperature changes on animals.
The genetic basis of crop domestication and improvement.
The evolution of reproductive strategies in animals.
The impacts of plastic pollution on terrestrial ecosystems.
The molecular mechanisms of stem cell differentiation and regeneration.
The ecological dynamics of predator-prey interactions.
The role of gut microbiota in the regulation of host metabolism.
The genetic basis of host-pathogen coevolution.
The evolution of social cognition and cooperation in animals.
The ecological and physiological effects of wildfires on ecosystems.
The molecular mechanisms of transcriptional regulation in eukaryotic cells.
The role of microorganisms in soil nutrient cycling and ecosystem functioning.
The genetic basis of plant-pathogen interactions.
The ecology and evolution of microbial communities in the ocean.
The physiological and behavioral effects of water pollution on aquatic organisms.
The molecular mechanisms of protein degradation and turnover.
The impact of urbanization on pollinator populations and plant-pollinator interactions.
The genetic basis of insecticide resistance in pests.
The evolution of animal cognition and perception.
The ecological and evolutionary dynamics of host-parasite interactions.
The role of epigenetic modifications in plant adaptation to environmental stress.
The physiological and behavioral effects of endocrine disruptors on animals.
The molecular mechanisms of DNA replication and repair.
The impact of ocean warming on coral reef ecosystems.
The genetic basis of animal personality traits.
The ecology and evolution of microbial symbioses in animals.
The physiological and behavioral effects of light quality on plants.
The molecular mechanisms of RNA editing and splicing.
The role of microbial communities in plant-pathogen interactions.
The ecological and evolutionary dynamics of seed dispersal.
The genetic basis of animal coloration and pattern.
The impact of climate change on plant phenology and productivity.
The molecular mechanisms of signal transduction in cells.
The role of microbial communities in the human gut-brain axis.
The ecology and evolution of animal migrations.
The physiological and behavioral effects of chemical pollution on animals.
The genetic basis of animal development and morphogenesis.
The evolution of animal social behavior and communication.
The ecological dynamics of plant-pollinator networks.
The molecular mechanisms of intracellular trafficking and transport.
The role of microbial communities in the degradation of pollutants.
The ecological and evolutionary dynamics of species interactions in ecological communities.
The role of epigenetics in cancer development and progression.
The molecular basis of antibiotic resistance in bacteria.
The impact of climate change on biodiversity and ecosystem functioning.
The genetic basis of aging and age-related diseases.
The evolution of social organization in primates.
The ecological dynamics of plant-fungal interactions.
The role of microbiota in immune system development and function.
The molecular mechanisms of DNA damage and repair.
The physiological and behavioral effects of climate change on marine organisms.
The genetic basis of human variation and diversity.
The evolution of sexual selection and mate choice in animals.
The ecological and evolutionary dynamics of species invasions.
The role of microbiota in brain function and behavior.
The molecular mechanisms of immune system activation and regulation.
The physiological and behavioral effects of pollution on wildlife.
The genetic basis of behavioral disorders and mental illness.
The evolution of plant-pollinator mutualisms.
The ecological dynamics of predator-prey coevolution.
The role of microbiota in metabolic diseases such as obesity and diabetes.
The molecular mechanisms of protein-protein interactions and signaling.
The genetic basis of complex traits such as intelligence and personality.
The evolution of animal communication and language.
The ecological and evolutionary dynamics of mutualistic interactions in ecological communities.
The role of microbiota in the development and maintenance of gut homeostasis.
The molecular mechanisms of neurotransmitter synthesis and release.
The physiological and behavioral effects of artificial light at night on wildlife.
The genetic basis of developmental disorders such as autism and ADHD.
The evolution of host-parasite coevolution and adaptation.
The ecological dynamics of plant-herbivore interactions.
The role of microbiota in the regulation of metabolism and energy balance.
The molecular mechanisms of membrane transport and signaling.
The physiological and behavioral effects of habitat fragmentation on wildlife.
The genetic basis of circadian rhythms and sleep disorders.
The evolution of animal cognition and decision-making.
The ecological and evolutionary dynamics of trophic cascades.
The role of microbiota in the development and function of the respiratory system.
The molecular mechanisms of epigenetic inheritance.
The physiological and behavioral effects of endocrine disruptors on wildlife.
The genetic basis of developmental plasticity and adaptation.
The evolution of animal social learning and culture.
The ecological dynamics of predator-prey interactions in aquatic systems.
The role of microbiota in the regulation of host immunity and inflammation.
The molecular mechanisms of RNA interference and gene silencing.
The physiological and behavioral effects of climate change on migratory animals.
The genetic basis of drug addiction and substance abuse disorders.
The evolution of animal cooperation and conflict resolution.
The ecological and evolutionary dynamics of niche construction.
The role of microbiota in the regulation of host-microbe interactions.
The molecular mechanisms of gene regulation by non-coding RNAs.
The role of epigenetics in gene expression and regulation.
The molecular mechanisms of DNA damage response and repair.
The impact of environmental toxins on human health.
The evolutionary origins of viruses and their impact on hosts.
The genetics of aging and age-related diseases.
The impact of ocean acidification on marine organisms.
The molecular basis of cancer development and progression.
The genetic basis of behavior in animals.
The impact of environmental stressors on plant growth and productivity.
The evolution of sex determination and sexual selection.
The role of the immune system in host-microbe interactions.
The molecular mechanisms of circadian rhythms and sleep.
The impact of air pollution on respiratory health.
The genetic basis of speciation and hybridization.
The role of neurotransmitters in brain function and behavior.
The ecological dynamics of microbial communities in soil.
The impact of climate change on biodiversity and ecosystem services.
The molecular mechanisms of viral entry, replication, and release.
The genetics of plant domestication and diversification.
The role of mitochondrial DNA in aging and disease.
The impact of deforestation on ecosystem functioning.
The molecular basis of drug addiction and treatment.
The genetic basis of adaptation and evolution in response to environmental change.
The role of gut-brain signaling in behavior and disease.
The impact of noise pollution on wildlife populations.
The genetic basis of plant morphology and development.
The role of the microbiome in disease susceptibility and resistance.
The ecological dynamics of plant-insect interactions.
The impact of agricultural practices on soil health and biodiversity.
The molecular mechanisms of gene regulation in development and disease.
The genetic basis of complex traits in humans and animals.
The role of cytokines in immune response and inflammation.
The ecological dynamics of microbial communities in aquatic ecosystems.
The impact of plastic waste on marine ecosystems.
The molecular mechanisms of genome stability and repair.
The genetics of rare and common genetic diseases.
The role of the endocannabinoid system in health and disease.
The ecological dynamics of competition and cooperation in populations.
The impact of light pollution on wildlife behavior and ecology.
The genetic basis of animal migration and navigation.
The role of the microbiome in host metabolism and energy balance.
The impact of climate change on agricultural productivity and food security.
The molecular mechanisms of epigenetic inheritance and transmission.
The genetics of human brain development and disorders.
The role of pheromones in animal communication and behavior.
The ecological dynamics of host-microbe-pathogen interactions.
The effect of diet and nutrition on gut microbiome diversity and composition.
The ecology and evolution of microbial interactions in the soil.
The role of epigenetic modifications in cancer development and progression.
The impact of climate change on marine biodiversity and ecosystem functioning.
The molecular mechanisms of mitochondrial respiration and ATP synthesis.
The role of non-coding RNAs in gene regulation and disease.
The evolution and diversification of flowering plants.
The effects of artificial light at night on animal behavior and physiology.
The genetic basis of adaptation to extreme environments.
The ecology and evolution of plant-microbe interactions.
The physiological and behavioral effects of noise pollution on wildlife.
The molecular mechanisms of DNA methylation and histone modification.
The role of microbial communities in the cycling of nutrients in aquatic ecosystems.
The evolution of animal color vision and perception.
The ecological and evolutionary dynamics of mutualistic interactions.
The impact of deforestation on soil fertility and carbon storage.
The molecular mechanisms of viral replication and pathogenesis.
The role of microorganisms in the biodegradation of plastics.
The ecology and evolution of microbial communities in the human gut.
The physiological and behavioral effects of climate change on birds.
The impact of invasive species on native ecosystems.
The genetic basis of developmental disorders and intellectual disabilities.
The evolution of animal behavior and communication in response to anthropogenic change.
The ecological dynamics of soil carbon sequestration and storage.
The role of microbial communities in the decomposition of organic matter.
The physiological and behavioral effects of air pollution on plants.
The molecular mechanisms of cellular differentiation and tissue development.
The ecology and evolution of plant-animal interactions.
The genetic basis of resistance to herbicides and pesticides in crops.
The impact of urbanization on bird diversity and distribution.
The role of microorganisms in the cycling of carbon and nitrogen in soil.
The ecological and evolutionary dynamics of invasive species interactions.
The physiological and behavioral effects of climate change on reptiles and amphibians.
The role of microbial communities in the degradation of petroleum hydrocarbons.
The genetic basis of plant development and growth.
The evolution of animal migration and dispersal.
The impact of land use change on freshwater biodiversity.
The molecular mechanisms of membrane transport and ion channels.
The role of microorganisms in the cycling of sulfur and phosphorus in soil.
The physiological and behavioral effects of ocean acidification on marine organisms.
The genetic basis of behavior and personality traits in humans.
The evolution of plant reproductive strategies and pollination systems.
The ecological and evolutionary dynamics of predator-prey coevolution.
The impact of environmental stressors on gene expression and epigenetics.
The evolution of sexual reproduction and mating systems in plants.
The role of microorganisms in bioremediation of contaminated sites.
The physiological and behavioral effects of climate change on fish.
The molecular mechanisms of chromatin remodeling and gene regulation.
The genetic basis of adaptation to high altitude environments.
The ecology and evolution of plant-insect interactions.
The impact of pesticide use on insect biodiversity and ecosystem functioning.
The role of microorganisms in nitrogen fixation and cycling.
The genetic basis of neurodegenerative diseases and cognitive decline.
The evolution of social behavior and cooperation in animals.
The ecological and evolutionary dynamics of plant invasions.
The physiological and behavioral effects of noise pollution on humans.
The molecular mechanisms of RNA splicing and alternative splicing.
The role of microorganisms in biogeochemical cycling of trace elements.
The genetic basis of adaptation to extreme temperatures.
The ecology and evolution of microbial communities in soil and water.
The impact of climate change on insect phenology and distribution.
The molecular mechanisms of protein folding and misfolding.
The role of microorganisms in biodegradation of environmental pollutants.
The evolution of animal cognition and intelligence.
The ecological and evolutionary dynamics of predator-prey interactions.
The impact of anthropogenic noise on marine mammals.
The role of microorganisms in biofilm formation and quorum sensing.
The genetic basis of speciation and hybridization in plants.
The evolution of parental care and offspring development in animals.
The ecological and evolutionary dynamics of food web interactions.
The physiological and behavioral effects of air pollution on human health.
The molecular mechanisms of transcriptional regulation and gene expression.
The role of microorganisms in plant growth promotion and disease suppression.
The genetic basis of adaptation to drought stress in crops.
The ecology and evolution of microbial interactions in the ocean.
The impact of land use change on soil erosion and nutrient cycling.
The molecular mechanisms of autophagy and programmed cell death.
The role of microorganisms in biodegradation of pharmaceuticals.
The genetic basis of immune system variation and disease susceptibility.
The evolution of animal social networks and communication systems.
The ecological and evolutionary dynamics of biodiversity loss.
The physiological and behavioral effects of light pollution on nocturnal animals.
The molecular mechanisms of DNA repair and genome stability.
The role of microorganisms in the production of biofuels and bioplastics.
The genetic basis of adaptation to salinity stress in plants.
The ecology and evolution of microbial symbioses with plants and animals.
The impact of climate change on plant-pollinator interactions.
The molecular mechanisms of cellular senescence and aging.
The role of microorganisms in biodegradation of synthetic organic compounds.
The genetic basis of variation in complex traits in humans.
The evolution of animal social behavior and cultural transmission
The genetic basis of cancer development and progression.
The role of microorganisms in the gut microbiome and human health.
The genetic basis of phenotypic plasticity and adaptation in plants.
The evolution of animal migration and navigation.
The ecological and evolutionary dynamics of community assembly.
The physiological and behavioral effects of light and dark cycles on circadian rhythms.
The molecular mechanisms of protein synthesis and degradation.
The role of microorganisms in nitrogen and carbon cycling in aquatic ecosystems.
The genetic basis of sex determination and differentiation in animals.
The ecology and evolution of predator-prey coevolution.
The impact of anthropogenic activities on marine biodiversity and ecosystems.
The role of microorganisms in bioleaching and biomining of metals.
The genetic basis of inherited disorders and genetic diseases.
The evolution of animal social behavior and communication systems.
The ecological and evolutionary dynamics of competition and coexistence.
The physiological and behavioral effects of endocrine disruptors on human health.
The molecular mechanisms of cell division and mitosis.
The role of microorganisms in biodegradation of plastics and synthetic materials.
The genetic basis of epigenetic inheritance and regulation.
The ecology and evolution of mutualistic symbioses in plants and animals.
The impact of habitat fragmentation on species diversity and ecosystem functioning.
The role of microorganisms in bioremediation of oil spills.
The genetic basis of drug resistance in pathogens and cancer cells.
The evolution of animal personality and individual variation.
The ecological and evolutionary dynamics of biotic interactions in freshwater ecosystems.
The physiological and behavioral effects of artificial sweeteners on human health.
The molecular mechanisms of intracellular trafficking and secretion.
The role of microorganisms in biocontrol of plant pathogens and pests.
The genetic basis of hybridization and introgression in animals and plants.
The ecology and evolution of plant-pollinator mutualisms.
The impact of climate change on marine ecosystems and fisheries.
The molecular mechanisms of genome editing and gene therapy.
The role of microorganisms in biogas production and carbon capture.
The genetic basis of developmental disorders and birth defects.
The evolution of animal coloration and camouflage.
The ecological and evolutionary dynamics of invasive species.
The physiological and behavioral effects of air pollution on wildlife.
The molecular mechanisms of signal transduction and cell signaling.
The role of microorganisms in biodegradation of pharmaceuticals and personal care products.
The genetic basis of reproductive isolation and speciation.
The ecology and evolution of microbial interactions with plants and insects.
The impact of climate change on bird migration and breeding patterns.
The molecular mechanisms of protein-protein interactions and protein complexes.
The role of microorganisms in bioremediation of heavy metals.
The evolution of animal cognition and learning.
The ecological and evolutionary dynamics of biodiversity hotspots.
The impact of ocean acidification on marine ecosystems.
The genetics of complex diseases and personalized medicine.
The evolution of plant defense mechanisms against herbivores.
The role of microorganisms in soil carbon sequestration.
The physiological and behavioral effects of light on plant growth and development.
The molecular mechanisms of cancer metastasis and invasion.
The ecology and evolution of microbial communities in the human body.
The impact of climate change on migratory bird populations.

About the author

Muhammad Hassan

Researcher, Academic Writer, Web developer

200+ Funny Research Topics

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Developing a Research Question

From Laurier Library.

Selecting and Narrowing a Topic

Choose an area of interest to explore. .

For you to successfully finish a research project, it is important to choose a research topic that is relevant to your field of study and piques your curiosity. The flip side is that curiosity can take you down long and winding paths, so you also need to consider scope in how to effectively cover the topic in the space that you have available. If there's an idea or concept you've recently learned that's stuck with you, that might be a good place to start !

Gather background information.

You may not know right away what your research question is - that's okay! Start out with a broad topic, and see what information is out there through cursory background research. This will help you explore possibilities and narrow your topic to something manageable. Do a few quick searches in OneSearch@IU or in other relevant sources. See what other researchers have already written to help narrow your focus.

Narrow your topic.

Once you have a sense of how other researchers are talking about the topics you’re interested, narrow down your topic by asking the 5 Ws

Who – population or group (e.g., working class, college students, Native Americans)
What – discipline or focus (e.g., anthropological or art history)
Where – geographic location (e.g., United States; universities; small towns; Standing Rock)
When – time period or era (17 th century; contemporary; 2017)
Why – why is the topic important? (to the class, to the field, or to you)

Broad topic: Native American representations in museums

Narrowed topic: Museum efforts to adhere to NAGPRA

Adapted from: University of Michigan. (2023 Finding and Exploring your topic. Retrieved from https://guides.lib.umich.edu/c.php?g=283095&p=1886086

From Topic to Research Question

So, you have done some background research and narrowed down your topic. Now what? Start to turn that topic into a series of questions that you will attempt to answer the course of your research. Keep in mind that you will probably end up changing and adjusting the question(s) you have as you gather more information and synthesize it in your writing. However, having a clear line of inquiry can help you maintain a sense of your direction, which will then in turn help you evaluate sources and identify relevant information throughout your research process.

Exploratory questions.

These are the questions that comes from a genuine curiosity about your topic. When narrowing down your topic, you got a good sense of the Who, What, When, and Where of things. Now it’s time to consider

Asking open-ended “how” and “why” questions about your general topic, which can lead you to better explanations about a phenomenon or concept
Consider the “so what?” of your topic. Why does this topic matter to you? Why should it matter to others? What are the implications of the information you’re discovering through the search process to the Who and the What of your topic?

Evaluate your research question.

Use the following to determine if any of the questions you generated would be appropriate and workable for your assignment.

Is your question clear ? Do you have a specific aspect of your general topic that you are going to explore further? Will the reader of your research be able to keep it in mind?
Is your question focused? Will you be able to cover the topic adequately in the space available? Are you able to concisely ask the question?
Is your question and arguable ? If it can be answered with a simple Yes or No, then dig deeper. Once you get to “it depends on X, Y, and Z” then you might be getting on the right track.

Hypothesize.

Once you have developed your research question, consider how you will attempt to answer or address it.

What connections can you make between the research you’ve read and your research question? Why do those connections matter?
What other kinds of sources will you need in order to support your argument?
If someone refutes the answer to your research question, what is your argument to back up your conclusion?
How might others challenge your argument? Why do those challenges ultimately not hold water?

Adapted from: George Mason University Writing Center. (2018). How to write a research question. Retrieved from https://writingcenter.gmu.edu/writing-resources/research-based-writing/how-to-write-a-research-question

Sample research questions.

A good research question is clear, focused, and has an appropriate level of complexity. Developing a strong question is a process, so you will likely refine your question as you continue to research and to develop your ideas.

Unclear : Why are social networking sites harmful?

Clear: How are online users experiencing or addressing privacy issues on such social networking sites as Facebook and TikTok?

Unfocused: What is the effect on the environment from global warming?

Focused: How is glacial melting affecting penguins in Antarctica?

Simple vs Complex

Too simple: How are doctors addressing diabetes in the U.S.?

Appropriately Complex: What are common traits of those suffering from diabetes in America, and how can these commonalities be used to aid the medical community in prevention of the disease?

General Online Reference Sources

Reference sources like dictionaries and encylopedias provide general information about various subjects. They also include definitions that may help you break down your topic and understand it better. Sources includes in these entries can be springboards for more in-depth research.

A note on citation: Reference sources are generally not cited since they usually consist of common knowledge (e.g. who was the first United States President). But if you're unsure whether to cite something it's best to do so. Specific pieces of information and direct quotes should always be cited.

Encyclopedias and specialized reference resources in: Arts, Biography, History, Information and Publishing, Law, Literature, Medicine, Multicultural Studies, Nation and World, Religion, Science, Social Science

Why Use References Sources

Reference sources are a great place to begin your research. They can help you:

gain an overview of a topic
explore potential research areas
identify key issues, publications, or authors in your research area

From here, you can narrow your search topic and look at more specialized sources.

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Last Updated: Dec 1, 2023 11:57 AM
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Perspective
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Published: 09 November 2023

Enduring questions in regenerative biology and the search for answers

Ashley W. Seifert ORCID: orcid.org/0000-0001-6576-3664 1 ,
Elizabeth M. Duncan ORCID: orcid.org/0000-0003-2003-6417 1 &
Ricardo M. Zayas ORCID: orcid.org/0000-0002-6272-0519 2

Communications Biology volume 6 , Article number: 1139 ( 2023 ) Cite this article

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Differentiation
Regeneration

The potential for basic research to uncover the inner workings of regenerative processes and produce meaningful medical therapies has inspired scientists, clinicians, and patients for hundreds of years. Decades of studies using a handful of highly regenerative model organisms have significantly advanced our knowledge of key cell types and molecular pathways involved in regeneration. However, many questions remain about how regenerative processes unfold in regeneration-competent species, how they are curtailed in non-regenerative organisms, and how they might be induced (or restored) in humans. Recent technological advances in genomics, molecular biology, computer science, bioengineering, and stem cell research hold promise to collectively provide new experimental evidence for how different organisms accomplish the process of regeneration. In theory, this new evidence should inform the design of new clinical approaches for regenerative medicine. A deeper understanding of how tissues and organs regenerate will also undoubtedly impact many adjacent scientific fields. To best apply and adapt these new technologies in ways that break long-standing barriers and answer critical questions about regeneration, we must combine the deep knowledge of developmental and evolutionary biologists with the hard-earned expertise of scientists in mechanistic and technical fields. To this end, this perspective is based on conversations from a workshop we organized at the Banbury Center, during which a diverse cross-section of the regeneration research community and experts in various technologies discussed enduring questions in regenerative biology. Here, we share the questions this group identified as significant and unanswered, i.e., known unknowns. We also describe the obstacles limiting our progress in answering these questions and how expanding the number and diversity of organisms used in regeneration research is essential for deepening our understanding of regenerative capacity. Finally, we propose that investigating these problems collaboratively across a diverse network of researchers has the potential to advance our field and produce unexpected insights into important questions in related areas of biology and medicine.

A cross-species analysis of systemic mediators of repair and complex tissue regeneration

Gene regulatory programmes of tissue regeneration

Dedifferentiation: inspiration for devising engineering strategies for regenerative medicine

Introduction.

Modern scientific research generally reflects Thomas Kuhn’s notion of normal science , whereby technological advances enable researchers to pursue incremental confirmations of existing theory 1 . This approach does, on occasion, produce unexpected insight into outstanding problems, but its fidelity to conventional frameworks discourages the sort of creative experimentation and custom tool-building that produces paradigm-shifting results. Moreover, deploying new technology just because it is available can create the illusion of advancement, i.e., posing questions that have already been answered with less-advanced methods but are proffered as unresolved in order to apply the latest sophisticated (and usually expensive) technology. This is often done with good intentions, e.g., the hope of discovering something new with more sensitive detection or detail, but ultimately does not actually remove the most critical barriers that must be surmounted to move a field forward 2 . Furthermore, this kind of “modern science” incentivizes specialization and, in doing so, focuses effort away from bigger questions that require interdisciplinary efforts and have the potential to advance multiple fields.

In an attempt to think beyond “ normal science , ” we wrote this perspective piece to synthesize and share ideas discussed at a Banbury Center workshop on enduring questions in regenerative biology (Box 1 ). As a group broadly representative of the regeneration field, we reflected on the significant progress made in the past four decades and discussed the types of ambitious community-led projects that we need to pursue to uncover answers to new and enduring questions. There was a strong feeling that by doing this collectively and with the input of experts from other disciplines, regeneration researchers would be better prepared to harness existing or new technologies and design experiments that can begin to address these questions. When scientific collectives assemble to examine major problems, it motivates collaborative efforts across research groups and disciplines. Knowledge creation in one field often spurs progress in related areas, generating benefits for science far beyond the original goals.

Despite the varied expertise among workshop participants and wide-ranging discussions about how regeneration occurs among diverse species, we found broad agreement on identifying several enduring, fundamental questions where scientists should direct their efforts. Importantly, our task was to identify common problems that are not overly reductionist or specific to a particular organism. In essence, we focused on the forest to identify major driving questions while at the same time considering why some trees remain undescribed, hidden, or unknown. We found common ground on the notion that regeneration remains vastly understudied, in part because the most commonly used model organisms do not have robust regenerative capacities. Unsurprisingly, there was no strong impetus for creating new technologies to specifically study regeneration; the enduring technological hurdle in our field is the application of specific transgenic tools to highly regenerative research models. Thus, the perspective put forth here represents a synthesis of focused discussions that aim to stimulate an exchange of ideas and future collaborations between experts in many fields, including regeneration.

Box 1 Banbury Center Workshop

The ideas presented in this paper emerged from discussions at a Cold Spring Harbor Laboratory Banbury Center workshop organized by the authors (for information about The Banbury Center, see https://www.cshl.edu/banbury/ ). The workshop (Enduring Questions in Regenerative Biology) convened biologists and technologists to consider how basic research can advance our understanding of what endows some species and tissues with regenerative capacity, discuss if new tools and technologies are needed to sustain progress in this endeavor, and to consider how these findings could create the next generation of regenerative therapeutics. The workshop participants worked together to identify enduring questions in regenerative biology and why they persist before exploring collaborative approaches to answer them. The three authors were joined at the Banbury Center workshop by Carrie Adler, Maria Barna, Jeff Biernaskie, Sarah Calve, Joshua Currie, Celina Juliano, Je Hyuk Lee, Malcolm Maden, Francesca Mariani, Phillip Newmark, Bret Pearson, Tania Rozario, Tatiana Sandoval Guzmán, Jennifer Simkin, Mansi Srivastava, Kryn Stankunas, and Bo Wang. We note that in addition to discussions at the Banbury Center, participants contributed to reviewing and editing this paper.

Which key processes comprise regeneration?

Despite general agreement for defining regeneration (see Box 2 ), what remains ill-defined is the set of component processes that comprise regeneration from induction to resolution. While it is clear that regeneration is induced by significant tissue loss or wounding, when and how regeneration-specific processes can be distinguished from those that occur during wound healing and fibrotic repair remain unresolved. Historically, many researchers studied tissue repair mechanisms holistically across diverse species despite varied healing outcomes, i.e., fibrotic or regenerative 3 . However, modern (1980s-present) wound/tissue repair research has largely been siloed from epimorphic regeneration research because studies on wound repair rely heavily on mice, rats, and humans (i.e., non-regenerative species in which wound healing normally generates scar tissue). Similarly, research into epimorphic regeneration has relied on a few highly regenerative invertebrate and vertebrate models (e.g., Hydra , planarians, zebrafish, salamanders). As regeneration research expands its scope to include new research organisms that can be genetically manipulated and maintained in a laboratory setting 4 or that enable comparisons of regenerative success and failure between closely related and divergent species, our definition of “regenerative capacity” needs re-evaluation. For instance, does a species’ “regenerative capacity” signify the inheritance of a single, albeit complex, trait or a combination of separate, interwoven processes? If the latter, are all component processes required for successful regeneration, or might some tissues/species omit one or more? Conversely, do all non-regenerative organisms diverge at the same stage of this progression? Ultimately, refining the definition of regenerative capacity returns us to a fundamental question: what are the component events that comprise regeneration? Defining these components allows one to determine the extent to which they share similarities with or are distinct from processes that occur during fibrotic repair. Thus, we identified a set of fundamental processes that occur across most regenerative species (summarized in Table 1 ).

After defining component processes common to regeneration, we considered how these events might vary across an ever-broadening set of organisms. For instance, complex tissue regeneration may be evolutionarily constrained such that the entire regenerative response, including all component processes, is canalized with low variation between species for any specific process or set of interrelated processes (Fig. 1a, b ). This could be true even if regenerative ability has evolved multiple times in different lineages. Conversely, regeneration could have arisen via convergent evolution (i.e., homoplasy) and variability among component processes may be large across the entire process set or for most of the processes (Fig. 1c ). Alternatively, variation across species could be relatively large for some processes yet low for others, i.e., high conservation of specific processes (Fig. 1d ). Defining the processes outlined in Table 1 as component parts of regeneration provides a framework to study each one across organisms and facilitates the generation of testable hypotheses to ask what is lacking (or modified) in non-regenerative organisms. For example, one testable hypothesis is that events one through five outlined in Table 1 constitute a general wound response that occurs in all animals, regardless of subsequent steps, with regeneration requiring a distinct mechanism that transitions tissues into regenerative healing (steps six through nine, Table 1 ). Another hypothesis is that specific events occur during the early wounding response to trigger regenerative healing.

a Two example species that exhibit epimorphic regeneration: Acomys cahirinus (spiny mouse) and Schmidtea mediterranea (freshwater planarian). Complex tissue regeneration of the ear pinna (spiny mouse) and head (planarian) is depicted as occurring from an initial tissue injury through complete regeneration. Individual processes as presented in Table 1 are contained within three general phases of regeneration: wound healing, blastema formation, and morphogenesis. Because the timescale over which these processes occur in individual species is highly variable, regeneration in a is depicted independent of time. b – d Three alternative hypotheses describing variability between comparable processes across regenerative species as a function of time. b Variability between component processes during the time course of regeneration is either low (i.e., genetic, molecular, and cellular mechanisms are highly conserved across species, bottom arrow) or high (mechanisms are not well conserved, upper arrow). c The initial injury response between species is very similar, but variability increases for mechanisms associated with cell activation, cell cycle progression, blastema formation, and morphogenesis, and then becomes more similar again during the differentiation and scaling phases of regeneration. The hypothesis represented in d asserts that variation between species is relatively large for processes that occur during wound healing, but low in the processes involved in blastema formation; after blastema formation, process variability may remain low (conserved) or increase (divergent).

In line with the second hypothesis, one enduring question is whether a particular injury signal predicts the final healing outcome. For example, is there a unique trigger for wound healing versus regeneration 5 ? Many investigators have advanced the hypothesis that particular immune cells and their products are specifically required for regeneration, independent of their role in regulating and resolving inflammation 6 . For instance, studies in several adult regeneration models suggest blocking immune cell infiltration (e.g., monocytes and macrophages) or depleting specific immune cell subtypes (e.g., macrophages) prevents normal wound healing and the transition to regenerative healing 7 , 8 , 9 , 10 , 11 . In contrast, removing similar immune cell types when trying to stimulate regeneration can enhance the response (microglia) 12 . However, it remains an open question if immune phenotypes exist that regulate and promote regeneration-specific processes. The hypothesis that regeneration-promoting immune cell states exist could be tested by comparing immune system responses across different types of injuries in the same species, i.e., where one injury induces regeneration and the other does not (e.g., lizard tails vs. limbs). This hypothesis could also be tested by comparing the immune response in different aged animals or closely related species in which identical tissues heal via regeneration and fibrotic repair, respectively. Comparing the regenerative response in divergent regenerative species may also offer insight into whether components of the immune response are permissive or instructive relative to regeneration.

Component processes and the transitions between them are also critical to define because they establish a framework for generating specific datasets (i.e., cell type and time-point specific) that can capture cell state changes to compare across species. Specifically, changes in chromatin state or genomic architecture, which impact gene regulatory networks (GRNs) and their outputs, may be broadly conserved at these cellular and temporal transitions 13 . Importantly, cell state changes accompanying reactivation of developmental genes can provide signposts for exploring chromatin states associated with activation or repression of gene expression and thus provide insight into both activation and constraint of regenerative ability 14 . These types of comparisons also lay the groundwork for evaluating cell-type evolution models as they relate to the presence or absence of regenerative capacity 15 , 16 . Lastly, breaking regeneration into component processes provides a framework for comparing cellular transitions as they occur during regeneration and embryonic development (Boxes 3 and 4 ).

Box 2 Regeneration, tissue renewal, and all things in between

When scientists use the term regeneration , they do not always distinguish between processes that share similar features or outcomes, making it difficult for researchers outside the field to understand the significance of a given experiment. For example, it has become popular for researchers to conduct “regeneration” experiments on amphibian and fish embryos or at different stages of imaginal disc development as a proxy for studying regeneration in adult animals 99 , 100 , 101 . However, most regeneration biologists agree that tissue repair in embryos reflects tissue restoration via embryonic regulation 102 , 103 . While experimental results using these models may provide insight into how specific signaling pathways respond to cell damage or loss, such embryonic “regeneration” is often restricted to an early developmental window when tissue morphogenesis is still ongoing and should not reflect the regenerative capacity of that species’ fully differentiated tissue. Moreover, we cannot assume the regulatory mechanisms used to rebuild tissue in embryos are the same as those needed to restore developmental potency to adult cells (see Box 3 ).

Those studying regeneration in animals and plants generally use the term “regeneration” to refer to reparative regeneration: the faithful replacement of mature tissues, organs, or body parts in response to injury to restore the original structure and function. However, Thomas Hunt Morgan specified two modes of reparative regeneration that were not sharply separated: epimorphosis and morphallaxis. He defined epimorphosis as that mode where the “ proliferation of material precedes the development of the new part ” and morphallaxis as the mode “…in which a part is transformed directly into a new organism or part of an organism without proliferation at the cut-surfaces ” 36 . Although some researchers have argued that a strict division does not exist between these two modes 104 , 105 , most agree that epimorphosis is likely occurring in most regenerative organisms. In contrast, morphallaxis might be restricted to specific species or tissues (e.g., in the planarian intestine 106 ). Animals such as flatworms deploy both modes in that a mass of new, proliferative tissue accumulates at the injury site prior to regeneration but cell re-arrangements also occur to integrate old and new cells and complete the regenerative process 107 , 108 . Regardless, these terms remain useful when discussing complex tissue or organ regeneration in response to injury.

The applicability of “epimorphic” regeneration becomes less clear when our attention turns to examples such as muscle or hair follicle replacement in mammals (popular in vivo models also referred to as regenerative phenomena). In fact, these examples and others wherein dedicated multipotent stem cells underpin the turnover of single lineage tissues (e.g., feathers, gastrointestinal lining, blood, etc.) were historically referred to as “physiological regeneration” and are more aptly examples of tissue homeostasis or renewal . Far from being unique, this type of tissue “regeneration” is ubiquitous among almost all multicellular eukaryotes, in contrast to the epimorphic regeneration capacity of complex tissues, organs, and body parts in select animals. Thus, we should be cautious when equating ubiquitous, homeostatic phenomena to those with a more restricted phylogenetic distribution and a spontaneous, irregular starting point (i.e., injury-induced epimorphic regeneration).

But what happens when our neatly divided paradigms collide? For example, invertebrates such as planarians and Hydra exhibit high tissue turnover and almost unlimited regenerative capacity (i.e., whole-body regeneration). Although their response to injury features hallmarks of epimorphic regeneration, including the accumulation of proliferating cells at the wound site, they also maintain pluripotent somatic cells that constantly replenish the entire animal, such that all their tissues (including those that are not typically replenished in vertebrates, like the central nervous system) are in a perpetual state of renewal. Nevertheless, such animals provide an opportunity for studying the intersection of regeneration, homeostatic tissue renewal, and repair as they apply to all organisms. These examples underscore how a term like regeneration can be used in reference to functionally different processes, even though the differences may seem nuanced to those outside the field. This is especially evident when defining the basic component processes that comprise regeneration (Table 1 ) and determining the degree to which examples of regeneration in diverse species (or life stages) represent convergent or homologous events.

Box 3 Where do developmental and regenerative processes most overlap?

In reconsidering regeneration as a set of fundamental processes starting with wound healing, it becomes apparent that to say regeneration merely recapitulates development is an oversimplification. Since early animal regeneration experiments and evidentiary support of cell theory swept aside preformationist notions of development, a major point of inquiry has been the degree to which development and regeneration represent similar events deployed during different life stages. Historically, the relationship between development and regeneration put one in service of the other, depending on the scientific era. For example, 19th century embryologists studied regeneration to better understand developmental processes. However, late 20th century technological advances for assessing gene expression and function provided the means for studying genetic interactions during embryonic development directly in the embryo. The rise of genetic model organisms to study development then, in turn, created both an opportunity to leverage these research models for studying regeneration and a framework to uncover the genetic basis for regeneration, an approach that still dominates the field today.

This more recent mode of inquiry has operated under the assumption that the evolution of the embryo predates the evolution of regeneration, and thus, researchers contextualize their studies by asking what developmental pathways are redeployed during regeneration. On the contrary, might regeneration have provided the molecular building blocks and genetic circuits for embryonic development? Observations made by a number of experimental embryologists have hinted that patterning processes regulating regeneration in metazoan embryos were already present in early unicellular organisms 36 , 109 , 110 . If viewed through contemporary molecular biology and genetics, it is possible that genetic circuits necessary to restore patterns in the first multicellular organisms were later co-opted to help build the embryo. While the evolution of molecular mechanisms underlying regeneration and embryonic development may echo the conundrum of the chicken or the egg, considering alternative hypotheses about their relationship has value for understanding how regenerative ability is missing or curtailed in some animals.

Box 4 The concept of de-differentiation

Despite being one of the most common terms used by the regeneration community, de-differentiation remains ambiguously defined conceptually and experimentally. When used in the context of a cell participating in regeneration, de-differentiation originally referred to a loss of the terminally differentiated state in favor of a reacquired capacity to proliferate (Table 1 ). Elizabeth Hay cautioned about the extension of de-differentiation to include expanded lineage plasticity anticipating that it would lead to terminological chaos 111 . However, many contemporary biologists extend the definition to imply the loss of a stable phenotype (or identity) and the reacquisition of cellular plasticity 112 (i.e., differentiation potential). Experimental evidence for the extended definition of de-differentiation, as defined here, is supported in part by studies leveraging scRNA-seq comparisons of tissue undergoing development versus those undergoing regeneration, where cells undergoing regeneration begin to resemble embryonic cells found in the developmental anlagen 14 . Conceptually, a useful metaphor revises Waddington’s epigenetic landscape model (where cells were originally envisioned to move downhill only) to accommodate cellular re-programming, as demonstrated in larval Xenopus cells and later by using the Yamanaka factors (Oct4, Sox2, Klf2, and c-Myc) to re-program somatic cells in mammals where cells are now known to possess the potential to move “back up the hill” and de-differentiate to a previously occupied state 113 , 114 , 115 , 116 . Is the modern definition of de-differentiation akin to cellular re-programming (an important, if semantic, distinction)? If de-differentiation is instead partial re-programming, how do cells partially re-program naturally? And are there specific regulatory factors that limit complete reversion to a pluripotent state? Does de-differentiation always imply at least partial cellular re-programming, or trans-differentiation, in which cells gain the potential to switch fates? These questions should challenge us to consider defining de-differentiation more precisely, including how it does or does not differ from re-programming. In doing so, we can ask functionally relevant questions. Which cell types undergo de-differentiation? Do multiple cell types have the capacity to de-differentiate in different contexts, or are there specialized cells that have the capacity to respond to injury signals and act as progenitor cells?

Another perplexing question is whether cells in animals with pluripotent somatic cells can (or ever) undergo de-differentiation. As evolution gave way to the germline-somatic division, did multiple differentiation strategies arise? For example, did one pathway lead to the evolution of adult stem cells (e.g., satellite cells, intestinal crypt cells, hematopoietic stem cells) while another evolved multipotent progenitors (e.g., pericytes and fibroblasts) as a means for tissue renewal? These and other questions could be tested experimentally by combining lineage tracing, single-cell dissociation, next-generation sequencing, and genomic profiling before and after injury and over sufficient time scales.

What constitutes the beginning of regeneration?

Cells detect and respond to injury regardless of the healing outcome (regeneration or scarring), which raises another outstanding question: to what degree do different healing trajectories overlap (Fig. 2a–d )? For example, the ERK/MAPK signaling pathway is rapidly induced upon tissue injury in both non-regenerating and regenerating species and inhibition of its activation impairs wound healing and regeneration 5 , 17 , 18 , 19 , 20 , 21 . What remains unclear is whether the requirement of ERK/MAPK signaling in regeneration directly results from its role in wound healing or if this pleiotropic pathway induces multiple downstream mechanisms that are separately required for multiple regeneration steps (Table 1 ). Similarly, are there inductive molecules with the dual capacity to promote regeneration and antagonize fibrosis? 22 In broader terms, is it possible to identify a set of conserved cellular and molecular mechanisms that initiate regeneration and thus define the “beginning” of regeneration? As discussed above, it remains unclear whether the early events of wound healing are common across most species and contexts with the unique regenerative response initiated later, or if the different healing trajectories (regeneration vs. scarring) are established during the healing process (Fig. 2c, d ). If the latter, how can we discover molecular signals and cell states specific to regeneration?

a , b Examples of variation in regenerative ability across species. a Tissue healing is quite different between closely related (~18 mya) Acomys cahirinus (spiny mouse) and Mus musculus (laboratory mouse; Adobe Stock Image used with educational license) where Acomys exhibit complex tissue regeneration in the ear pinna and identical injuries heal with scar tissue (and no regeneration) in Mus . b While two flatworm species Schmidtea mediterranea (orange) and Dendrocoelum lacteum (gray) are capable of head regeneration, D. lacteum exhibits poor head regeneration from posterior fragments ( S. mediterranea has near limitless regenerative ability from any fragment). c Comparing regeneration and fibrotic repair, the early events that occur prior to new tissue formation could be similar between species, only to diverge as mechanisms specific to regeneration or fibrotic repair are activated. In the example presented, this divergence occurs immediately prior to activation of a developmental state (i.e., blastema formation), although under this hypothesis it could occur later. d An alternative is that regenerative and fibrotic healing are evolutionarily distinct and thus upon injury two different healing trajectories, and their mechanistic underpinnings, are expressed.

To distinguish between regenerative responses and more general repair processes, it can be useful to identify events that occur during both regeneration and embryonic development. As embryogenesis unfolds in a temporal sequence beginning from fertilization, tissues, and organs arise at precise positions and prescribed times based on a specific developmental plan. Although it is also difficult to ascribe an initiating event in organ development, developmental biologists largely agree that the formation of a tissue anlagen or primordium is associated with precursor cells that are competent to receive inductive signals. In response to inductive signals (cell-autonomous or non-cell-autonomous), precursor cells launch a developmental program and self-organize into tissues comprising a diverse array of differentiated cell types. Thus, it may be appropriate to consider the beginning of regeneration per se as the point when injury-activated cells accumulate at the injury site and adopt a development-like state (Table 1 ). This would align the beginning of regeneration with anlagen formation and distinguish wound healing from events specific to regeneration (Fig. 2c ).

In support of this proposition, data from salamanders suggests that injury-induced cell accumulation is necessary but insufficient for regeneration (reviewed in ref. 23 ). Across countless experiments, researchers performed surgical interventions to study how nerve-secreted signals regulate the regenerative response in ambystomid salamanders and newt limbs 24 , 25 . These results show that wound healing and proliferative cell accumulation occur after denervating a limb, but aggregated cells fail to progress to morphogenesis. In further support of this idea, inhibiting certain signaling pathways (e.g., Wnt and Hedgehog signaling) allows damaged tissue to repair, but regeneration does not occur 26 , 27 , 28 . Together, these findings support the concept that the ability to accumulate proliferative cells is a necessary but insufficient feature that distinguishes wound healing processes from regeneration. Instead, it suggests the transition to regeneration is characterized by proliferative cells acquiring the ability to undergo patterning, differentiation, and growth, a state often referred to as blastema formation 29 . However, data linking signaling pathways and nerves to regenerative competence also points to the existence of other essential cellular and molecular events that are required for regeneration to begin in a robust and recognizable way 26 , 27 , 28 . Thus, while the blastema is a common element of what may represent an evolutionarily conserved regenerative feature, it also highlights the critical need to determine which specific cellular and molecular characteristics of the local cellular environment are essential for regeneration to proceed.

The discussion of molecular signals that initiate regeneration evokes broader questions about what initiates the start of regeneration. For example, how is the amount of loss or damage requiring regeneration detected? Are specific regenerative programs only initiated after significant cell loss? If so, what are the mechanisms that activate them? There are many unknowns regarding injury-sensing mechanisms. Are there particular molecules or physiological changes communicating the amount or extent of tissue damage? Does the loss of cell-cell contacts act additively or in parallel to chemical sensing mechanisms? Does the new interaction of cells from different anatomical positions stimulate the regenerative program 30 , 31 , 32 ? Overall, the common theme that emerges from these questions is the need to expand data collection on regenerative ability within and across species, particularly by adding data from more examples of failed or intermediate regenerative success. More comprehensive data will allow researchers to better identify cellular, molecular, and functional commonalities in successful regenerative processes versus unsuccessful ones.

What constitutes the end of a regenerative process?

Indisputably, the most desirable outcome of a regeneration process is to regain tissue shape and function. Thus, understanding and defining when and how a regenerative process restores a functional state is equally important to determining how it starts. Most descriptions of tissue or whole-body regeneration indicate that repair processes shift to a remodeling and growth/scaling phase after the initial expansion of cellular material and patterning 33 . But exactly how regeneration restores form and function is not clearly defined. For example, as cells accumulate and proliferate, how do they appropriately regulate pathways that terminate cell cycle progression and how is this balanced with tissue scaling? Work on the Hippo pathway has demonstrated that its signals can be modulated to regulate growth during development 34 . A similar use of this pathway likely controls growth during regeneration 34 , 35 . However, precisely clarifying when regenerative healing and tissue restoration shift to a growth phase and identifying the molecular mechanisms that regulate this transition is a major objective for our field.

One possibility is that the end of regeneration recapitulates the patterning and growth of embryonic organs, where growth ultimately becomes regulated at the organismal level. For example, regeneration in molting animals (e.g., crustaceans) produces a miniature facsimile of the original appendage, which is only capable of additional growth upon subsequent molts 36 , 37 , 38 . In zebrafish, caudal fin regeneration is generally consistent with the overall size of the animal, but genetic mutants do exist in which regenerating fins lose their allometry and produce dramatically overgrown fins 39 . Nonetheless, regeneration generally restores missing tissues, their structures, and their functions, suggesting that although the precise mechanisms underlying the integration of new and existing tissue may vary across species, they achieve a common output.

In trying to understand why regeneration is absent in some animal species or tissue types, one hypothesis is that regeneration initiators are missing or not sufficiently activated, while another suggests that some animals lack the capacity to create restorative cell states. Another hypothesis is that mechanisms that normally terminate phases of regenerative healing have been co-opted to inhibit regeneration completely. For example, the evolution of “molecular brakes” in some animals may have rendered certain tissues regeneration-incompetent (e.g., heart muscle and the auditory epithelium) 40 . The acquisition of molecular breaks is also observed within an animal’s lifetime: neonatal mammals can regenerate a subset of tissues, including cardiac muscle 41 . Notably, cardiac muscle has been observed to regenerate in newborn mice for approximately one week before this ability is lost 42 . Could this apparent loss of regenerative ability as the animal ages result from inhibitory mechanisms that halt a specific component process? Comparisons across regenerative versus non-regenerative species/tissues are likely to assist in exploring this hypothesis 29 . In addition, a greater emphasis on pinpointing mechanisms that terminate or inhibit regenerative processes in cases where regeneration appears to be interrupted or halted after successful initiation may have profound implications for understanding how reduced regenerative capacity evolved in certain animal lineages.

Notably, unbridled overgrowth of regenerating tissue is rarely observed, supporting the hypothesis that regenerative species have mechanisms that provide tight control over proliferation and morphogenesis. Furthermore, reports of tumors in highly regenerative species are uncommon in the literature, although not unknown (reviewed in 43 , 44 ). Neoplasms can be induced in newts 45 and zebrafish (reviewed in 46 ), and epidermal neoplasms occur with some frequency in captive salamander colonies (see “De-Mystifying Salamander Cancers” Facebook group). In spite of these observations, the idea that highly regenerative organisms live tumor-free and are resistant to developing cancer remains a widely held belief 43 , 47 . Interestingly, epimorphic regeneration often requires highly conserved pathways that are associated with cancer, and disrupting tumor suppressor genes such as Hippo, p53, or PTEN in planarians and zebrafish can occasionally lead to the formation of tumor-like structures 48 , 49 , 50 , 51 . Thus, while the incidence of significant, bona fide tumorigenesis in highly regenerative animals appears low, it seems likely that pathways commonly dysregulated in human cancer are tightly controlled during regenerative healing 52 , 53 , 54 , 55 . Alternatively, the expansion of tumor suppressor gene families in mammals may correlate with their reduced ability to regenerate 54 . For example, the human ARF protein produced as an alternately spliced gene product from the p16 locus appears to be absent from the genomes of many regenerative species 54 . In addition, injecting newt myotubes with a plasmid encoding the human tumor suppressor p16 INK4a blocks de-differentiation and cell cycle re-entry 56 . Therefore, tumor suppressor genes may represent another layer of complexity that negatively regulates regenerative responses in mammals. Unraveling the functional relationship between tumor suppression, cell cycle control, and regeneration will require either in vivo genome editing or the introduction of genetically edited cells. However, these tools are currently limited to only a few regenerative organisms.

How does patterning happen across different scales to generate proportioned organs and tissues?

Understanding the mechanisms by which organisms set and restore size and shape is a formidable challenge in development and regeneration. Evidence from divergent organisms indicates that patterning and growth during regeneration depend on the activation of major components of developmental GRNs and signaling pathways. For example, a conserved role for Wnt signaling in re-establishing polarity during regeneration is supported by work in many regeneration systems, including Hydra , acoels, planarians, and amphibians 13 , 27 , 57 , 58 . Despite redeploying conserved developmental pathways, these processes need to operate on very different timescales and, in some cases, across orders of magnitude in scale, which remains difficult to reconcile with current knowledge about patterning in fields of cells.

In one illustration of how organisms can cope with scaling problems, Drosophila embryos balance cell proliferation and apoptosis to regulate proportion during development. Specifically, Bicoid protein is distributed in a gradient across the developing embryos and organizes anterior development 59 , 60 . Yet classic experiments revealed that increases in Bicoid dosage levels, which expand the anterior fate map of the embryo and should give rise to patterning defects, can produce normal larvae 60 . This restoration of proper proportion is driven by increased cell death in the expanded anterior regions, suggesting that the embryos have mechanisms for sensing and adjusting the relative proportion of anterior fated cells 61 . Cell death has also been implicated as a key process required in Hydra , planarian, and mammalian liver regeneration 62 . But how do cells detect when there are too few or too many cells and adjust the rate of proliferation or cell death? How do they maintain the correct ratio of specific cell types, particularly in a replacement tissue that must match the scale of the existing animal? Clearly, these are complex, challenging problems that are relevant to both development and regeneration, making experiments in one context informative for the other.

Besides balancing cell proliferation and death to achieve a proper number of building blocks, injured tissues must specify the fates of new cells and rearrange them appropriately to establish tissue size, proportion, and function. One historical view of how this is accomplished is that cells carry information in a Cartesian code to interpret positional details, and this code is deployed in response to morphogen gradients for pattern formation 63 . A molecular version of this theory is that cells have different chromatin and transcriptomic states based on their developmental history and can both emit and respond to signals in their local environment. Therefore, overall patterning can vary depending on the type or strength of the signals present and the state of cells interpreting the morphogenic cues. A striking example of the importance of this type of injury-induced communication is the dysregulation of canonical Wnt signaling in planarians, which disrupts anteroposterior polarity and leads to the regeneration of ectopic heads or tails 57 . In addition, the Wnt-signaling pathway also plays a role in regulating the proportion of new tissues, as disrupting the striatin-interacting phosphatase and kinase (STRIPAK) complex increases worm length by expanding the posterior wnt1 signaling center and dysregulating axial scaling 64 .

Important regeneration and growth signals are likely not restricted to secreted ligands and well-known signaling pathways. They likely involve ECM components, biomechanical inputs, redox state fluctuations, and changes in metabolic states 65 , 66 , 67 , 68 . Ion sensing has also been linked to organ size and regeneration 69 . For example, the zebrafish mutant longfin exhibits fin overgrowth due to ectopic expression of the ion channel Kcnh2a 39 . Thus, ion sensing and regulation may be a genetically encoded and tunable mechanism for “reading” positional information and producing the correct amount of growth. However, we do not yet know what controls the strength of different types of signals in different contexts and how the regulatory pathways in development might differ from those activated during regeneration. Additionally, although particular signaling pathways may be conserved across contexts, the exact cellular and molecular mechanisms in which they are deployed may differ depending on the size, proportion, and types of tissue being replaced. To this end, embryos typically develop on a much smaller scale than the replacement tissue that is produced during restorative regeneration, so while embryonic pathways may be re-used during regeneration, there are likely key mechanistic differences in how they are employed during the latter.

Is regeneration driven by gene regulatory modules that are conserved across species?

One rapidly expanding area of interest in regeneration biology is the application of genomic tools to understand how gene expression is regulated over time, in different injury and tissue contexts, and between species. Many recent studies have focused on identifying regulatory elements, particularly enhancers, that are potentially unique or specifically activated after injury in regenerative organisms/tissues (see Box 5 ). These efforts are rational extensions of studies showing that enhancers are sites of dynamic genome interactions with gene promoters during cell fate transitions in various developmental contexts and organisms 70 , 71 , 72 , 73 , 74 . Further, the genetic tools and cell culture systems used routinely in Drosophila and ex vivo mammalian cells to dissect regulatory mechanisms are not yet optimized in most highly regenerative organisms. Thus, it is reasonable to use paradigms emerging from traditional models as the basis for targeted experiments in regenerative organisms as a starting point for uncovering gene regulatory modules that function during regeneration. However, given that the genome regulatory mechanisms that drive regenerative processes and transitions may be different from those operating in non-regenerative species, it is also critical for our field to expand our hypotheses and approaches beyond those that emerge from studies in common animal models. To ensure that we identify the key regulatory mechanisms, including potentially novel ones, that control essential regenerative processes, we must invest the resources needed to customize problem-specific tools in regenerative models. For example, there are chemical biology tools (e.g., degrons, azide-labeled non-canonical amino acids) that are not commonly used in our fields but would allow us to address specific, mechanistic questions arising from decades of observational and functional studies.

Any individual group studying genome regulation during regeneration will likely find that evaluating all possible mechanisms of genome regulation is a formidable challenge. Thus, innovation and impactful discovery in this area will particularly benefit from coordinated interaction and collaboration across research groups so that experimental design and genomic data collection can be readily comparable. In addition, a broad view of genomic regulation across multiple regenerative species will allow us to identify conserved mechanisms, even if the specific genetic modules they activate or silence are different 13 (Fig. 3 ). Whether there is greater conservation of upstream genome regulatory mechanisms, the specific proteins orchestrating them, or the genetic modules they target is not likely to have a single or simple answer (Fig. 3 ). However, we can better distinguish which molecular mechanisms are functionally significant during regeneration by focusing on how specific genetic modules that are known to be activated and essential for regeneration are regulated in regenerative versus non-regenerative contexts.

a In this model, specific gene modules (e.g., coding genes and enhancers) are conserved among various species but regulated differently after injury. This model represents situations where specific genes (e.g., gene X) are present in multiple species, but only activated after injury in regenerative species. It also reflects the possibility that injury-induced genes are activated by different mechanisms in different regenerative species. b In this model, injury induces similar genome regulatory mechanisms (e.g., changes in histone modifications and the expression of pioneering transcription factors) but they have different functional outcomes due to evolutionary differences in the presence and arrangement of specific genetic modules (e.g., the enhancer is only present at this locus in regenerative organisms).

For example, in the regeneration-competent zebrafish retina, expression of transcription factor ascl1 is induced upon retinal injury and required for retinal regeneration 75 , 76 . Interestingly, Ascl1 is conserved in mice and required for their retinal development 77 , 78 , but Ascl1 expression is not induced after injury of the non-regenerative mouse retina 79 , 80 . This observation inspired experiments in which Asl1 was ectopically expressed in explanted adult mouse retinas 81 . However, although Ascl1 functions like a pioneer factor in some ways (e.g., inducing transcription of some relevant target genes), ectopic Ascl1 expression alone was insufficient to induce functional de-differentiation, proliferation, or redifferentiation in injured mouse retinas 81 . Yet, importantly, further experiments found that treatment of mouse retinas with ectopic Ascl1 expression in combination with a histone deacetylase (HDAC) inhibitor (which broadly increases genome accessibility) is significantly more successful in activating productive de-differentiation, proliferation, and redifferentiation of mouse cells 82 . These results are exciting, as they suggest it is indeed possible to reactivate existing genes and induce regeneration in non-regenerative tissues 83 . Nevertheless, many unanswered questions remain: are HDACs facilitating Ascl1 binding to the genome, and if so, at which loci? Which of these newly bound Ascl1 loci are functionally important, and for which steps in the regenerative processes? Why is the induced regeneration of mouse retinas still less robust than the endogenous regeneration process in zebrafish? What regulatory mechanisms or targeted gene expression programs are missing (or inhibitory)? Experiments addressing these specific questions have the potential to both further our understanding of retinal regeneration and uncover widely conserved molecular mechanisms that regulate essential genetic modules in other regenerative contexts.

From a broader perspective, there are many interesting and unanswered questions regarding the role of genome structure and function in regenerative processes. For example, is it relevant that many regenerative organisms, including vertebrates (e.g., axolotls) and invertebrates (e.g., planarians), have large genomes containing significant amounts of repetitive sequence? What do the repetitive sequences signify? Are these sequences serving as regulatory platforms for transcription factor binding, or do they play more instructive roles in regulating cellular plasticity? Interestingly, studies in mammalian stem cells and early embryos suggest that transient activation of repetitive regions plays a major role in regulating gene expression and chromatin state at critical developmental transitions 84 , 85 , 86 . Are similar mechanisms operating during cell state transitions after an injury? As with the other major knowledge gaps in our field, more comparative studies across species and developmental contexts will be needed to unravel the answers to these questions.

Box 5 Challenges in identifying regeneration-specific enhancers

Enhancers are non-coding regulatory elements in the genome that interact with gene loci to regulate their expression. A single enhancer typically contains recognition motifs for multiple transcription factors (TFs). It also requires the productive binding of multiple TFs for activation 117 , 118 , 119 , a feature that facilitates the integration of various inputs (e.g., cell type-specific TFs and signaling-specific TFs) to create a new output. Studies in regenerative animals and tissues have uncovered enhancers that show increased chromatin accessibility after injury and whose increased openness correlates with the expression of wound-induced genes 120 , 121 , 122 , 123 , 124 , 125 , 126 . In some of these studies 122 , 123 , 125 , 126 , activated enhancers were identified based on a gain of histone H3 lysine 27 acetylation (H3K27ac), a modification known to mark active enhancers across multiple organisms and contexts 127 , 128 . Recently, other studies have used the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) 120 , 125 or tissue-specific transgenes expressing epitope-tagged histones 121 to detect wound-induced increases in genome accessibility or nucleosome turnover, respectively, at specific genomic loci. Together, these approaches are an important first step in addressing whether there are unique regulatory elements in the genomes of regenerative organisms and specific injury-activated mechanisms in these animals that can reactivate developmental GRNs (Fig. 3 ).

These pioneering studies raise important questions that require further investigation. First, are the methods used sufficient for identifying functional enhancers? Emerging data from the transcription field suggest that these approaches may only identify a small subset of functional enhancers due, in part, to the following considerations: (1) individual genes are often regulated by multiple enhancers 129 , 130 , 131 , (2) enhancers identified by chromatin profiling do not correlate very well with assays of enhancer function 132 and, similarly, (3) not all injury-activated enhancers were found to be functionally required for regeneration 123 . Additional transgenic approaches will be needed to pinpoint injury-regulated enhancers that are functionally relevant and work in synergy with other genomic regulatory elements.

Second, how can we best identify the TFs that activate or are recruited to injury-regulated enhancers? Although sequence analysis of regulatory regions marked by specific chromatin modifications or increased accessibility is a valid and worthwhile first step, these algorithms depend on known TF recognition site information. As a result, they cannot identify the binding sites of novel TFs or even TFs with poorly characterized binding motifs. It is also very likely that regeneration enhancers will require the binding of multiple TFs to activate downstream genes specifically and robustly. In addition to using established omics methodologies, our field should optimize and develop biochemical approaches that address specific, outstanding questions about gene activation upon injury and during the regenerative response. Although such methods can be technically challenging, especially when starting with complex tissues versus cultured cells, the rewards would be high if they allowed the identification of relevant binding factors at essential gene loci.

Third, what are the mechanisms that specifically activate these enhancers after an injury? For example, does it matter which histone acetyltransferase (i.e., p300 or CBP) acetylates a specific enhancer upon injury? Also, is H3K27ac even required for the activation and function of these enhancers? The latter question is particularly relevant given that enhancer H3K27ac is dispensable for activating gene expression in static cell culture but necessary for cell state transitions such as differentiation 133 . Another recent study reaffirmed that not all enhancers require the same core cofactors, such as the H3K27ac acetyltransferases p300 and CBP, to activate downstream target genes 134 . Although high conservation makes H3K27ac a convenient mark for identifying enhancer locus candidates, it will be necessary for our field to generate custom reagents that recognize the homologs of other cofactors, e.g., Mediator and BRD4, in regenerative species to identify those enhancers that are specifically regulated by these other complexes.

Concluding remarks

One of the oldest and most enduring questions identified by regenerative and developmental biologists is why regenerative ability is unevenly distributed among metazoans 87 . Why, with over two centuries of regeneration research behind us and major technological advances in molecular biology, next-generation sequencing, and genetic engineering occurring at an ever-quickening pace, does this problem continue to challenge our field? First, evolutionary problems that span large phylogenetic distances are notoriously difficult to address experimentally, and debates about the adaptive nature of regenerative ability remain unresolved. Second, tackling this question necessitates expanding the diversity of species used in regeneration studies 88 , which faces significant financial and practical barriers. Understandably, many scientists prefer to take advantage of the extensive toolkits available in a small subset of genetic model organisms and shy away from the risks associated with learning or developing a new model system. Of course, the decision to study a new model or species should be driven by scientific questions.

In our discussions at the Banbury workshop, there was broad consensus that comparative studies are essential to identifying the possible cell states, mechanisms, and functions critical for those processes outlined in Table 1 . Unfortunately, experimental workflows designed for one species are rarely practical across multiple species due to various confounding factors (e.g., regeneration timing, anatomical differences, genome quality disparities, the need for species-specific expertise, etc.). Instead, the field should invest in collectively designing experimental pipelines that can be deployed across species in individual laboratories with high fidelity. Such pipelines would use existing technologies to generate data that may not be significant in any species but could synergize to generate and address many testable hypotheses. Multi-species studies can provide a platform to test the widely held position that a core regenerative program is conserved among metazoans, and its unequal distribution reflects loss and re-emergence in distant lineages. As the number of species used in regeneration research grows within taxonomic groups and across increasingly distant lineages, it will also provide an opportunity to rigorously examine if the alternative hypothesis may be true: that regeneration has independently evolved in numerous lineages. If the latter hypothesis was shown to be true, it would radically expand potential avenues to explore in regenerative therapies.

Adding to the complexity of discovering the mechanistic basis for interspecific differences in regenerative ability, cellular changes associated with aging (e.g., mutations, metabolism, epigenetic states) are gaining recognition as complementary problems with solutions that may help unlock the potential to stimulate regeneration in humans. Suggestively, animals with the capacity for whole-body regeneration, like Hydra and planarians, appear to be negligibly senescent 89 , animals with indeterminate growth have high regenerative ability 90 , and recent work in spiny mice suggests connective tissue cells from these regenerative mammals are highly resistant to stress-induced cellular senescence 91 . Moreover, long-lived animals and those with post-metamorphic life stages often lose or have diminished regenerative capacities in adulthood compared to their fetal, neonatal, or juvenile life stages 92 . While the cellular and molecular mechanisms underlying this loss remain poorly understood, possibilities include changes in how cells sense injury signals, cell-autonomous features that prevent cell activation or cell state alternations, or a decline in homeostatic cellular and tissue renewal (Table 1 and Box 2 ). Together, it is increasingly clear that major advances in dissecting the molecular logic of regeneration (and reconstructing it in humans) cannot occur by studying a handful of organisms. Instead, expanding the collective effort of many research labs across an increasing diversity of organisms can provide answers to some enduring questions in animal biology while potentially unlocking new breakthroughs in human regenerative medicine. Excellent examples of such efforts include comparative studies contrasting species of salamanders, fish, or flatworms 8 , 93 , 94 , 95 , 96 , which revealed cellular and molecular insights.

Of course, science at the scale we suggest requires coordination across organisms, labs, and institutions, not to mention a financial strategy to support such activities. Additionally, there is a need for investigators to invest in multiple approaches to rigorously test conclusions on which subsequent studies are based. Rigor and reproducibility, once a cornerstone of the scientific method, have taken a distant backseat to novelty 97 . Potentially insightful work demonstrated in one model system, or species is strengthened, not weakened, through repeated experimental testing by multiple groups and through testing in other regenerative organisms 98 . We must ask this of our field. Cross-species study reproduction and hypothesis testing provide another dimension related to the conservation and canalization of regenerative mechanisms. To understand the fundamental principles of regeneration, we urge our peers and other scientists to revisit some of the most enduring questions in our field.

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Acknowledgements

We thank the Banbury Center for providing an amazing atmosphere for our vintage workshop experiment and, specifically, Rebecca Leshan for her backing and encouragement. We acknowledge Genentech and The Cold Spring Harbor Laboratory Corporate Sponsor Program for supporting the workshop. In addition to input from all attendees of the Banbury Workshop that informed this perspective article, we thank Francesca Mariani for significant editorial input. In a better-designed version of itself, academia would encourage the type of collaborative effort that went into this paper to be formally recognized with co-authorship. While nothing precludes this arrangement, how current conflict of interest (COI) declarations impact review procedures for grant proposals and promotion panels created unavoidable conflicts among participants to be co-authors. Lastly, we would like to thank John (Jack) Allen and Kelly Ross for their perspectives on an early version of this paper. Research in A.W. Seifert’s lab is funded by NIH grants R01 AR070313, R21 DE028070, the ASAP Collaborative Research Network through the Michael J. Fox Foundation, and DOD CDMRP 6W81XWH2110503. Research in R.M. Zayas’s lab is funded by NIH grant R01 GM135657. Research in E.M. Duncan’s lab is funded through NIH grant R35 GM142679.

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A.W.S., E.M.D., and R.M.Z. recorded detailed notes of discussions from the Banbury Workshop (Box 1 ). A.W.S., E.M.D., and R.M.Z. used the compiled notes to draft the manuscript. R.M.Z. incorporated suggested edits from meeting participants into the drafted manuscript. A.W.S. and E.M.D. created the illustrations with input from R.M.Z. A.W.S., E.M.D., and R.M.Z. revised the document and discussed all major revisions.

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Seifert, A.W., Duncan, E.M. & Zayas, R.M. Enduring questions in regenerative biology and the search for answers. Commun Biol 6 , 1139 (2023). https://doi.org/10.1038/s42003-023-05505-7

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Published: 26 November 2018

The 150 most important questions in cancer research and clinical oncology series: questions 94–101

Edited by Cancer Communications

Cancer Communications

Cancer Communications volume 38 , Article number: 69 ( 2018 ) Cite this article

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Since the beginning of 2017, Cancer Communications (former title: Chinese Journal of Cancer ) has published a series of important questions regarding cancer research and clinical oncology, to provide an enhanced stimulus for cancer research, and to accelerate collaborations between institutions and investigators. In this edition, the following 8 valuable questions are presented. Question 94. The origin of tumors: time for a new paradigm? Question 95. How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma? Question 96. Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor? Question 97. What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction? Question 98. Is high local concentration of metformin essential for its anti-cancer activity? Question 99. How can we monitor the emergence of cancer cells anywhere in the body through plasma testing? Question 100. Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells? Question 101. Is cell migration a selectable trait in the natural evolution of carcinoma?

Until now, the battle against cancer is still ongoing, but there are also ongoing discoveries being made. Milestones in cancer research and treatments are being achieved every year; at a quicker pace, as compared to decades ago. Likewise, some cancers that were considered incurable are now partly curable, lives that could not be saved are now being saved, and for those with yet little options, they are now having best-supporting care. With an objective to promote worldwide cancer research and even accelerate inter-countries collaborations, since the beginning of 2017, Cancer Communications (former title: Chinese Journal of Cancer ) has launched a program of publishing 150 most important questions in cancer research and clinical oncology [ 1 ]. We are providing a platform for researchers to freely voice-out their novel ideas, and propositions to enhance the communications on how and where our focus should be placed [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. In this edition, 8 valuable and inspiring questions, Question 94–101, from highly distinguished professionals from different parts of the world are presented. If you have any novel proposition(s) and Question(s), please feel free to contact Ms. Ji Ruan via email: [email protected].

Question 94: The origin of tumors: time for a new paradigm?

Background and implications.

“There is no worse blind man than the one who doesn’t want to see. There is no worse deaf man than the one who doesn’t want to hear. And there is no worse madman than the one who doesn’t want to understand.” —Ancient Proverb

In the past half-century, cancer biologists have focused on a dogma in which cancer was viewed as a proliferative disease due to mechanisms that activate genes (oncogenes) to promote cell proliferation or inactivate genes (tumor suppressor genes) to suppress tumor growth. In retrospect, these concepts were established based on functional selections, by using tissue culture (largely mouse NIH 3T3 cells) for the selection of transformed foci at the time when we knew virtually nothing about the human genome [ 14 ]. However, it is very difficult to use these genes individually or in combinations to transform primary human cells. Further, the simplified view of uncontrolled proliferation cannot explain the tumor as being a malignant organ or a teratoma, as observed by pathologists over centuries. Recently, the cancer genomic atlas project has revealed a wide variety of genetic alterations ranging from no mutation to multiple chromosomal deletions or fragmentations, which make the identification of cancer driver mutations very challenging in a background of such a massive genomic rearrangement. Paradoxically, this increase the evidences demonstrating that the oncogenic mutations are commonly found in many normal tissues, further challenging the dogma that genetic alteration is the primary driver of this disease.

Logically, the birth of a tumor should undergo an embryonic-like development at the beginning, similar to that of a human. However, the nature of such somatic-derived early embryo has been elusive. Recently, we provided evidence to show that polyploid giant cancer cells (PGCCs), which have been previously considered non-dividing, are actually capable of self-renewal, generating viable daughter cells via amitotic budding, splitting and burst, and capable of acquisition of embryonic-like stemness [ 15 , 16 , 17 ]. The mode of PGCC division is remarkably similar to that of blastomere, a first step in human embryogenesis following fertilization. The blastomere nucleus continuously divides 4–5 times without cytoplasmic division to generate 16–32 cells and then to form compaction/morulae before developing into a blastocyst [ 18 ]. Based on these data and similarity to the earliest stage of human embryogenesis, I propose a new theory that tumor initiation can be achieved via a dualistic origin, similar to the first step of human embryogenesis via the formation of blastomere-like cells, i.e. the activation of blastomere or blastomere-like cells which leads to the dedifferentiation of germ cells or somatic cells, respectively, which is then followed by the differentiation to generate their respective stem cells, and the differentiation arrest at a specific developmental hierarchy leading to tumor initiation [ 19 ]. The somatic-derived blastomere-like cancer stem cell follows its own mode of cell growth and division and is named as the giant cell cycle. This cycle includes four distinct but overlapping phases: the initiation, self-renewal, termination, and stability phases. The giant cell cycle can be tracked in vitro and in vivo due to their salient giant cell morphology (Fig. 1 ).

One mononucleated polyploid giant cancer cell (PGCC) in the background of regular size diploid cancer cells. The PGCC can be seen to be at least 100 times larger than that of regular cancer cells

This new theory challenges the traditional paradigm that cancer is a proliferative disease, and proposes that the initiation of cancer requires blastomere-like division that is similar to that of humans before achieving stable proliferation at specific developmental hierarchy in at least half of all human cancers. This question calls for all investigators in the cancer research community to investigate the role of PGCCs in the initiation, progression, resistance, and metastasis of cancer and to look for novel agents to block the different stages of the giant cell cycle.

The histopathology (phenotype) of cancers has been there all the time. It is just the theory of cancer origin proposed by scientists that changes from time to time. After all, trillions of dollars have been invested in fighting this disease by basing on its genetic origin in the past half-century, yet, little insight has been gained [ 14 ]. Here are two quotes from Einstein: “Insanity: doing the same thing over and over again expecting different results”, and “We cannot solve our problems with the same thinking we used when created them”.

In short, it is time to change our mindset and to start pursuing PGCCs, which we can observe under the microscope. But with very little understanding about these cells, it is time for a shift in paradigm.

Jinsong Liu.

Affiliation

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4095, USA.

Email address

[email protected]

Question 95: How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the world with a dismal 5-year overall survival rate of less than 5%; which has not been significantly improved since the past decades. Although surgical resection is the only option for curative treatment of PDAC, only 15%–20% of patients with PDAC have the chance to undergo curative resection, leaving the rest with only palliative options in hope for increasing their quality of life; since they were already at unresectable and non-curative stages at their first diagnosis.

The lack of specific symptoms in the early-stage of PDAC is responsible for rendering an early diagnosis difficult. Therefore, more sensitive and specific screening methodologies for its early detection is urgently needed to improve its diagnosis, starting early treatments, and ameliorating prognoses. The diagnosis so far relies on imaging modalities such as abdominal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP), and positron emission tomography (PET). One may propose to screen for pancreatic cancer in high-risk populations, which is highly recommended, however screening intervention for all the people is not a wise choice; when considering the relatively low prevalence of PDAC, and the difficulty for diagnosing it in its early stage [ 20 ].

Therefore, alternative diagnostic tools for early detection of PDAC are highly expected. Among the biomarkers currently used in clinical practice, carbohydrate antigen 19–9 (CA19–9) is among the most useful one for supporting the diagnosis of PDAC, but it is neither sufficiently sensitive nor specific for its early detection. Yachida et al. reported in 2010 that the initiating mutation in the pancreas occurs approximately two decades before the PDAC to start growing in distant organs [ 21 ], which indicates a broad time of the window of opportunity for the early detection of PDAC. With the advancement in next-generation sequencing technology, the number of reported studies regarding novel potential molecular biomarkers in bodily fluids including the blood, feces, urine, saliva, and pancreatic juice for early detection of PDAC has been increasing. Such biomarkers may be susceptible to detect mutations at the genetic or epigenetic level, identifying important non-coding RNA (especially microRNA and long non-coding RNA), providing insights regarding the metabolic profiles, estimating the tumor level in liquid biopsies (circulating free DNA, circulating tumor cells and exosomes), and so on.

Another approach to identifying biomarkers for the early detection of pancreatic cancer is using animal models. In spontaneous animal models of pancreatic cancer, such as Kras-mutated mouse models, it is expected that by high throughput analyses of the genetic/epigenetic/proteomic alterations, some novel biomarkers might be able to be identified. For instance, Sharma et al. reported in 2017 that the detection of phosphatidylserine-positive exosomes enabled the diagnosis of early-stage malignancies in LSL-Kras G12D , Cdkn2a lox/lox : p48 Cre and LSL-Kras G12d/+ , LSL-Trp R172H/+ , and P48 Cre mice [ 22 ].

These analyses in clinical samples or animal models hold the clues for the early detection of PDAC, however, further studies are required to validate their diagnostic performance. What’s most important, will be the lining-up of these identified prospective biomarkers, to validate their sensitivities and specificities. This will determine their potential for widespread clinical applicability, and hopefully, accelerate the early diagnosis of PDAC.

Mikiya Takao 1,2 , Hirotaka Matsuo 2 , Junji Yamamoto 1 , and Nariyoshi Shinomiya 2 .

1 Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan; 2 Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

E-mail address

[email protected]; [email protected]; [email protected]; [email protected]

Question 96: Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers, and nearly half of the patients had metastatic PDAC when they are initially diagnosed. When they are accompanied by metastatic tumors, unlike most solid cancer, PDAC cannot be cured with primary surgical resection alone [ 23 , 24 ]. Also, since PDAC has poor responses to conventional therapies, improvements in adjunctive treatment approach including chemo- and immuno-therapy are earnestly required. From this standpoint, recent results regarding the differences in the molecular evolution of pancreatic cancer subtypes provide a new insight into its therapeutic development [ 25 ], which may lead to the improvement of the prognosis of not only metastatic PDAC but also of locally advanced or recurrent PDAC.

In fact, new chemotherapeutic regimens such as the combination of gemcitabine with nab-paclitaxel and FOLFIRINOX have been reported to show improved prognosis despite a lack of examples of past successes in the treatment of patients with metastatic PDAC who had undergone R0 resection [ 26 ]. While many mutations including KRAS , CDKN2A , TP53, and SMAD4 are associated with pancreatic carcinogenesis, no effective molecular targeted drug has been introduced in the clinical setting so far. A recent report of a phase I/II study on refametinib, a MEK inhibitor, indicated that KRAS mutation status might affect the overall response rate, disease control rate, progression-free survival, and overall survival of PDAC in combination with gemcitabine [ 27 ].

While immunotherapy is expected to bring a great improvement in cancer treatment, until now, immune checkpoint inhibitors have achieved limited clinical benefit for patients with PDAC. This might be because PDAC creates a uniquely immunosuppressive tumor microenvironment, where tumor-associated immunosuppressive cells and accompanying desmoplastic stroma prevent the tumor cells from T cell infiltration. Recently reported studies have indicated that immunotherapy might be effective when combined with focal adhesion kinase (FAK) inhibitor [ 28 ] or IL-6 inhibitor [ 29 ], but more studies are required to validate their use in clinical practice.

As such, we believe that if the dynamic monitoring of drug sensitivity/resistance in the individual patients is coupled with precision treatment based on individualized genetics/epigenetics/proteomics alterations in the patients’ tumor, this could improve the treatment outcomes of PDAC.

Mikiya Takao 1,2 , Hirotaka Matsuo 2 , Junji Yamamoto 1 , and Nariyoshi Shinomiya 2.

Question 97: What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?

Recently, cancer immunotherapy has shown great clinical benefit in multiple types of cancers [ 30 , 31 , 32 ]. It has provided new approaches for cancer treatment. However, it has been observed that only a fraction of patients respond to immunotherapy.

Much effort has been made to identify markers for immunotherapeutic response. Tumor mutation burden (TMB), mismatch repair (MMR) deficiency, PD-L1 expression, and tumor infiltration lymphocyte (TIL) have been found to be associated with an increased response rate in checkpoint blockade therapies. Unfortunately, a precise prediction is still challenging in this field. Moreover, when to stop the treatment of immunotherapy is an urgent question that remains to be elucidated.

In other words, there is no available approach to determine if a patient has generated a good immune response against the cancer after immunotherapy treatments. All of these indicate the complexity and challenges that reside for implementing novel man-induced cancer-effective immune response therapeutics. A variety of immune cells play collaborative roles at different stages to recognize antigens and eventually to generate an effective anti-cancer immune response. Given the high complexity of the immune system, a rational evaluation approach is needed to cover the whole process. Moreover, we need to perfect vaccine immunization and/or in vitro activation of T cells to augment the function of the immune system; particularly the formation of immune memory.

Edison Liu 1 , Penghui Zhou 2 , Jiang Li 2 .

1 The Jackson Laboratory, Bar Harbor, ME 04609, USA; 2 Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.

[email protected]; [email protected]; [email protected]

Question 98: Is high local concentration of metformin essential for its anti-cancer activity?

Metformin was approved as a first line of anti-diabetic drug since decades. Interestingly, the fact that clinical epidemiological studies have shown that metformin can reduce the risk of a variety of cancers stimulates considerable recognition to explore its anticancer activity.

Although the in vitro and in vivo experimental results have demonstrated that metformin can have some potential anti-tumor effects, more than 100 clinical trials did not achieve such desirable results [ 33 ]. We and others believe that the main problem resides in the prescribing doses used. For cancer treatment, a much higher dose may be needed for observing any anti-tumor activities, as compared to the doses prescribed for diabetics [ 34 , 35 , 36 ].

Further, if the traditional local/oral administration approach is favored, the prescribed metformin may not be at the required dose-concentration once it reaches the blood to have the effective anti-cancer activities. We, therefore, propose that intravesical instillation of metformin into the bladder lumen could be a promising way to treat for bladder cancer, at least. We have already obtained encouraging results both in vitro and in vivo experiments, including in an orthotopical bladder cancer model [ 36 , 37 ]. Now, we are waiting to observe its prospective clinical outcome.

Mei Peng 1 , Xiaoping Yang 2 .

1 Department of Pharmacy, Xiangya Hospital, Central South University. Changsha, Hunan 410083, P. R. China; 2 Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, P. R. China.

[email protected]; [email protected]

Question 99: How can we monitor the emergence of cancer cells anywhere in the body through plasma testing?

The early detection of cancer is still a relentless worldwide challenge. The sensitivity and specificity of traditional blood tumor markers and imaging technologies are still to be greatly improved. Hence, novel approaches for the early detection of cancer are urgently needed.

The emergence of liquid biopsy technologies opens a new driveway for solving such issues. According to the definition of the National Cancer Institute of the United States, a liquid biopsy is a test done on a sample of blood to look for tumorigenic cancer cells or pieces of tumor cells’ DNA that are circulating in the blood [ 38 ]. This definition implies two main types of the current liquid biopsy: one that detects circulating tumor cells and the other that detects non-cellular material in the blood, including tumor DNA, RNA, and exosomes.

Circulating tumor cells (CTCs) are referred to as tumor cells that have been shed from the primary tumor location and have found their way to the peripheral blood. CTCs were first described in 1869 by an Australian pathologist, Thomas Ashworth, in a patient with metastatic cancer [ 39 ]. The importance of CTCs in modern cancer research began in the mid-1990s with the demonstration that CTCs exist early in the course of the disease.

It is estimated that there are about 1–10 CTCs per mL in whole blood of patients with metastatic cancer, even fewer in patients with early-stage cancer [ 40 ]. For comparison, 1 mL of blood contains a few million white blood cells and a billion erythrocytes. The identification of CTCs, being in such low frequency, requires some special tumoral markers (e.g., EpCAM and cytokeratins) to capture and isolate them. Unfortunately, the common markers for recognizing the majority of CTCs are not effective enough for clinical application [ 41 ]. Although accumulated evidences have shown that the presence of CTCs is a strong negative prognostic factor in the patients with metastatic breast, lung and colorectal cancers, detecting CTCs might not be an ideal branch to hold on for the hope of early cancer detection [ 42 , 43 , 44 , 45 ].

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the circulatory system, which is mainly derived from the tumor cell death through necrosis and/or apoptosis [ 46 ]. Given its origin, ctDNA inherently carries cancer-specific genetic and epigenetic aberrations, which can be used as a surrogate source of tumor DNA for cancer diagnosis and prognostic prediction. Ideally, as a noninvasive tumor early screening tool, a liquid biopsy test should be able to detect many types of cancers and provide the information of tumor origin for further specific clinical management. In fact, the somatic mutations of ctDNA in different types of tumor are highly variable, even in the different individuals with the same type of tumor [ 47 ]. Additionally, most tumors do not possess driver mutations, with some notable exceptions, which make the somatic mutations of ctDNA not suitable for early detection of the tumor.

Increased methylation of the promoter regions of tumor suppressor genes is an early event in many types of tumor, suggesting that altered ctDNA methylation patterns could be one of the first detectable neoplastic changes associated with tumorigenesis [ 48 ]. ctDNA methylation profiling provides several advantages over somatic mutation analysis for cancer detection including higher clinical sensitivity and dynamic range, multiple detectable methylation target regions, and multiple altered CpG sites within each targeted genomic region. Further, each methylation marker is present in both cancer tissue and ctDNA, whereas only a fraction of mutations present in cancer tissue could be detected in ctDNA.

In 2017, there were two inspiring studies that revealed the values of using ctDNA methylation analysis for cancer early diagnosis [ 49 , 50 ]. After partitioning the human genome into blocks of tightly coupled CpG methylation sites, namely methylation haplotype blocks (MHBs), Guo and colleagues performed tissue-specific methylation analyses at the MHBs level to accurately determine the tissue origin of the cancer using ctDNA from their enrolled patients [ 49 ]. In another study, Xu and colleagues identified a hepatocellular carcinoma (HCC) enriched methylation marker panel by comparing the HCC tissue and blood leukocytes from normal individuals and showed that methylation profiles of HCC tumor DNA and matched plasma ctDNA were highly correlated. In this study, after quantitative measurement of the methylation level of candidate markers in ctDNA from a large cohort of 1098 HCC patients and 835 normal controls, ten methylation markers were selected to construct a diagnostic prediction model. The proposed model demonstrated a high diagnostic specificity and sensitivity, and was highly correlated with tumor burden, treatment response, and tumor stage [ 50 ].

With the rapid development of highly sensitive detection methods, especially the technologies of massively parallel sequencing or next-generation sequencing (NGS)-based assays and digital PCR (dPCR), we strongly believe that the identification of a broader “pan-cancer” methylation panel applied for ctDNA analyses, probably in combination with detections of somatic mutation and tumor-derived exosomes, would allow more effective screening for common cancers in the near future.

Edison Liu 1 , Hui-Yan Luo 2 .

[email protected]; [email protected]

Question 100: Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?

Though several anticancer agents are approved to treat different types of cancers, their full potentials have been limited due to the occurrence of drug resistance. Resistance to anticancer drugs develops by a variety of mechanisms, one of which is increased drug efflux by transporters. The ATP-binding cassette (ABC) family drug efflux transporter P-glycoprotein (P-gp or multi-drug resistance protein 1 [MDRP1]) has been extensively studied and is known to play a major role in the development of multi-drug resistance (MDR) to chemotherapy [ 51 ]. In brief, overexpressed P-gp efflux out a wide variety of anticancer agents (e.g.: vinca alkaloids, doxorubicin, paclitaxel, etc.), leading to a lower concentration of these drugs inside cancer cells, thereby resulting in MDR. Over the past three decades, researchers have developed several synthetic P-gp inhibitors to block the efflux of anticancer drugs and have tested them in clinical trials, in combination with chemotherapeutic drugs. But none were found to be suitable enough in overcoming MDR and to be released for marketing, mainly due to the side effects associated with cross-reactivity towards other ABC transporters (BCRP and MRP-1) and the inhibition of CYP450 drug metabolizing enzymes [ 52 , 53 ].

On the other hand, a number of phytochemicals have been reported to have P-gp inhibitory activity. Moreover, detailed structure–activity studies on these phytochemicals have delineated the functional groups essential for P-gp inhibition [ 53 , 54 ]. Currently, one of the phytochemicals, tetrandrine (CBT-1 ® ; NSC-77037), is being used in a Phase I clinical trial ( http://www.ClinicalTrials.gov ; NCT03002805) in combination with doxorubicin for the treatment of metastatic sarcoma. Before developing phytochemicals or their derivatives as P-gp inhibitors, they need to be investigated thoroughly for their cross-reactivity towards other ABC transporters and CYP450 inhibition, in order to avoid toxicities similar to the older generation P-gp inhibitors that have failed in clinical trials.

Therefore, the selectivity for P-gp over other drug transporters and drug metabolizing enzymes should be considered as important criterias for the development of phytochemicals and their derivatives for overcoming MDR.

Mohane Selvaraj Coumar and Safiulla Basha Syed.

Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.

[email protected]; [email protected]

Question 101: Is cell migration a selectable trait in the natural evolution of carcinoma?

The propensity of solid tumor malignancy to metastasize remains the main cause of cancer-related death, an extraordinary unmet clinical need, and an unanswered question in basic cancer research. While dissemination has been traditionally viewed as a late process in the progression of malignant tumors, amount of evidence indicates that it can occur early in the natural history of cancer, frequently when the primary lesion is still barely detectable.

A prerequisite for cancer dissemination is the acquisition of migratory/invasive properties. However, whether, and if so, how the migratory phenotype is selected for during the natural evolution of cancer and what advantage, if any, it may provide to the growing malignant cells remains an open issue. The answers to these questions are relevant not only for our understating of cancer biology but also for the strategies we adopt in an attempt of curbing this disease. Frequently, indeed, particularly in pharmaceutical settings, targeting migration has been considered much like trying “to shut the stable door after the horse has bolted” and no serious efforts in pursuing this aim has been done.

We argue, instead, that migration might be an intrinsic cancer trait that much like proliferation or increased survival confers to the growing tumor masses with striking selective advantages. The most compelling evidence in support for this contention stems from studies using mathematical modeling of cancer evolution. Surprisingly, these works highlighted the notion that cell migration is an intrinsic, selectable property of malignant cells, so intimately intertwined with more obvious evolutionarily-driven cancer traits to directly impact not only on the potential of malignant cells to disseminate but also on their growth dynamics, and ultimately provide a selective evolutionary advantage. Whether in real life this holds true remains to be assessed, nevertheless, work of this kind defines a framework where the acquisition of migration can be understood in a term of not just as a way to spread, but also to trigger the emergence of malignant clones with favorable genetic or epigenetic traits.

Alternatively, migratory phenotypes might emerge as a response to unfavorable conditions, including the mechanically challenging environment which tumors, and particularly epithelial-derived carcinoma, invariably experience. Becoming motile, however, may not per se being fixed as phenotypic advantageous traits unless it is accompanied or is causing the emergence of specific traits, including drug resistance, self-renewal, and survival. This might be the case, for example, during the process of epithelial-to-mesenchymal transition (EMT), which is emerging as an overarching mechanism for dissemination. EMT, indeed, may transiently equip individual cancer cells not only with migratory/invasive capacity but also with increased resistance to drug treatment, stemness potential at the expanse of fast proliferation.

Thus, within this framework targeting pro-migratory genes, proteins and processes may become a therapeutically valid alternative or a complementary strategy not only to control carcinoma dissemination but also its progression and development.

Giorgio Scita.

IFOM, The FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), School of Medicine, University of Milan, Via Festa del Perdono 7, 20122, Italy.

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Cancer Communications. The 150 most important questions in cancer research and clinical oncology series: questions 94–101. Cancer Commun 38 , 69 (2018). https://doi.org/10.1186/s40880-018-0341-9

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Tumor origin
Polyploid giant cancer cell
Pancreatic ductal adenocarcinoma
Liquid biopsy
Spontaneous animal model
Chemotherapy
Immunotherapy
Precision treatment
Vaccine immunization
Circulating tumor cell
Circulating tumor DNA
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Epithelial-to-mesenchymal transition
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Quantum physics proposes a new way to study biology – and the results could revolutionize our understanding of how life works

Quantum Biology Tech (QuBiT) Lab, Assistant Professor of Electrical and Computer Engineering, University of California, Los Angeles

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Imagine using your cellphone to control the activity of your own cells to treat injuries and disease. It sounds like something from the imagination of an overly optimistic science fiction writer. But this may one day be a possibility through the emerging field of quantum biology.

Over the past few decades, scientists have made incredible progress in understanding and manipulating biological systems at increasingly small scales, from protein folding to genetic engineering . And yet, the extent to which quantum effects influence living systems remains barely understood.

Quantum effects are phenomena that occur between atoms and molecules that can’t be explained by classical physics. It has been known for more than a century that the rules of classical mechanics, like Newton’s laws of motion, break down at atomic scales . Instead, tiny objects behave according to a different set of laws known as quantum mechanics .

For humans, who can only perceive the macroscopic world, or what’s visible to the naked eye, quantum mechanics can seem counterintuitive and somewhat magical. Things you might not expect happen in the quantum world, like electrons “tunneling” through tiny energy barriers and appearing on the other side unscathed, or being in two different places at the same time in a phenomenon called superposition .

I am trained as a quantum engineer . Research in quantum mechanics is usually geared toward technology. However, and somewhat surprisingly, there is increasing evidence that nature – an engineer with billions of years of practice – has learned how to use quantum mechanics to function optimally . If this is indeed true, it means that our understanding of biology is radically incomplete. It also means that we could possibly control physiological processes by using the quantum properties of biological matter.

Quantumness in biology is probably real

Researchers can manipulate quantum phenomena to build better technology. In fact, you already live in a quantum-powered world : from laser pointers to GPS, magnetic resonance imaging and the transistors in your computer – all these technologies rely on quantum effects.

In general, quantum effects only manifest at very small length and mass scales, or when temperatures approach absolute zero. This is because quantum objects like atoms and molecules lose their “quantumness” when they uncontrollably interact with each other and their environment. In other words, a macroscopic collection of quantum objects is better described by the laws of classical mechanics. Everything that starts quantum dies classical. For example, an electron can be manipulated to be in two places at the same time, but it will end up in only one place after a short while – exactly what would be expected classically.

In a complicated, noisy biological system, it is thus expected that most quantum effects will rapidly disappear, washed out in what the physicist Erwin Schrödinger called the “ warm, wet environment of the cell .” To most physicists, the fact that the living world operates at elevated temperatures and in complex environments implies that biology can be adequately and fully described by classical physics: no funky barrier crossing, no being in multiple locations simultaneously.

Chemists, however, have for a long time begged to differ. Research on basic chemical reactions at room temperature unambiguously shows that processes occurring within biomolecules like proteins and genetic material are the result of quantum effects. Importantly, such nanoscopic, short-lived quantum effects are consistent with driving some macroscopic physiological processes that biologists have measured in living cells and organisms. Research suggests that quantum effects influence biological functions, including regulating enzyme activity , sensing magnetic fields , cell metabolism and electron transport in biomolecules .

How to study quantum biology

The tantalizing possibility that subtle quantum effects can tweak biological processes presents both an exciting frontier and a challenge to scientists. Studying quantum mechanical effects in biology requires tools that can measure the short time scales, small length scales and subtle differences in quantum states that give rise to physiological changes – all integrated within a traditional wet lab environment.

In my work , I build instruments to study and control the quantum properties of small things like electrons. In the same way that electrons have mass and charge, they also have a quantum property called spin . Spin defines how the electrons interact with a magnetic field, in the same way that charge defines how electrons interact with an electric field. The quantum experiments I have been building since graduate school , and now in my own lab, aim to apply tailored magnetic fields to change the spins of particular electrons.

Research has demonstrated that many physiological processes are influenced by weak magnetic fields. These processes include stem cell development and maturation , cell proliferation rates , genetic material repair and countless others . These physiological responses to magnetic fields are consistent with chemical reactions that depend on the spin of particular electrons within molecules. Applying a weak magnetic field to change electron spins can thus effectively control a chemical reaction’s final products, with important physiological consequences.

Currently, a lack of understanding of how such processes work at the nanoscale level prevents researchers from determining exactly what strength and frequency of magnetic fields cause specific chemical reactions in cells. Current cellphone, wearable and miniaturization technologies are already sufficient to produce tailored, weak magnetic fields that change physiology , both for good and for bad. The missing piece of the puzzle is, hence, a “deterministic codebook” of how to map quantum causes to physiological outcomes.

In the future, fine-tuning nature’s quantum properties could enable researchers to develop therapeutic devices that are noninvasive, remotely controlled and accessible with a mobile phone. Electromagnetic treatments could potentially be used to prevent and treat disease, such as brain tumors , as well as in biomanufacturing, such as increasing lab-grown meat production .

A whole new way of doing science

Quantum biology is one of the most interdisciplinary fields to ever emerge. How do you build community and train scientists to work in this area?

Since the pandemic, my lab at the University of California, Los Angeles and the University of Surrey’s Quantum Biology Doctoral Training Centre have organized Big Quantum Biology meetings to provide an informal weekly forum for researchers to meet and share their expertise in fields like mainstream quantum physics, biophysics, medicine, chemistry and biology.

Research with potentially transformative implications for biology, medicine and the physical sciences will require working within an equally transformative model of collaboration. Working in one unified lab would allow scientists from disciplines that take very different approaches to research to conduct experiments that meet the breadth of quantum biology from the quantum to the molecular, the cellular and the organismal.

The existence of quantum biology as a discipline implies that traditional understanding of life processes is incomplete. Further research will lead to new insights into the age-old question of what life is, how it can be controlled and how to learn with nature to build better quantum technologies.

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People with more copies of ribosomal DNA may have higher risks of developing disease

Ribosomal DNA (rDNA) is present in hundreds of copies in the genome, but has not previously been part of genetic analyses. A new study of 500,000 individuals indicates that people who have more copies of rDNA are more likely to develop inflammation and diseases during their lifetimes.

Standard genetic analysis techniques have not studied areas of the human genome that are repetitive, such as ribosomal DNA (rDNA), a fundamental part of the molecular mechanism which makes proteins in cells. A new study, led by Vardhman Rakyan and Francisco Rodriguez-Algarra from Queen Mary University of London's Blizard Institute in collaboration with David Evans from The University of Queensland's Institute for Molecular Bioscience, has discovered that genetic disposition to disease can be found in these previously understudied areas of the genome. These results suggest that wider genome analysis could bring opportunities for preventative diagnostics, novel therapeutics, and greater insight into the mechanism of different human diseases.

In this study, co-funded by Barts Charity, Rosetrees Trust, and the Biotechnology and Biological Sciences Research Council (BBSRC), samples from 500,000 individuals in the UK Biobank project were analysed. Researchers used new whole genome sequencing (WGS) techniques to identify differences in numbers of copies of rDNA in each sample, and compared them with other health metrics and medical records.

The researchers found that the number of copies of rDNA in an individual showed strong statistical association with well-established markers of systemic inflammation -- such as Neutrophil-to-Lymphocyte ratio (NLR), Platelet-to-Lymphocyte ratio (PLR), and Systemic Immune-Inflammation index (SII). These statistically significant associations were seen in the genomes of individuals of different ethnicities, suggesting a common indicator for risks of future disease.

rDNA copy number was also linked with an individual's kidney function within the sample of individuals of European ancestry. A similar effect was seen in samples from other ancestries, but further research using larger sample sizes will be needed to confirm this connection.

Professor Vardhman Rakyan, from the Genomics and Child Health in the Blizard Institute at Queen Mary, said: "Our research highlights the importance of analysing the whole genome to better understand the factors impacting on our health. This study is also an example of how having access to large biobanks allows us to make unexpected discoveries, and provides new avenues for harnessing the power of genetics to understand human diseases."

Professor David Evans, from The University of Queensland's Institute for Molecular Bioscience, said: "Geneticists have long struggled to fully explain the genetic basis of many common complex traits and diseases. Our work suggests that at least part of this missing heritability resides in difficult to sequence regions of the genome such as those encoding ribosomal copy number variation."

Victoria King, Director of Funding and Impact at Barts Charity, said: "We're delighted to have supported this work which could lead to better prevention and treatment for many different diseases. Using samples from UK Biobank participants, this study highlights the exciting potential of examining previously overlooked areas of the genome."

Human Biology
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Materials provided by Queen Mary University of London . Note: Content may be edited for style and length.

Journal Reference :

Francisco Rodriguez-Algarra, David M. Evans, Vardhman K. Rakyan. Ribosomal DNA copy number variation associates with hematological profiles and renal function in the UK Biobank . Cell Genomics , 2024; 100562 DOI: 10.1016/j.xgen.2024.100562

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The state of advanced recycling in 2024

Recorded by:

Written by:

Marcian Lee, Ph.D.

Kristin Marshall

Associate Research Director

May 13, 2024

Over the past several years, advanced plastic recycling has been one of the most asked-about topics at Lux. This is not surprising as the plastics industry inches closer to deadlines for recycled content mandates and sustainability pledges. Advanced recycling allows for the recycling of previously unrecyclable waste streams and could potentially output virgin-like quality recyclates. However, despite a growing demand for recycled plastics and better plastic recycling technologies, developers have largely struggled to commercialize.

A recent research brief written by Lux Analyst Dr. Marcian Lee, tracks a total of 169 scale-up announcements (including pilot or demonstration plants) across the Americas, EMEA, and APAC and finds over 6 Mtonne/y announced advanced recycling capacity, with 2 Mtonne/y of this capacity not having a clear timeline or is planned for beyond 2026. This constitutes a three-fold increase in capacity over the next three years.

The technologies considered are (1) pyrolysis (heating of plastic waste in an inert environment to recover a liquid hydrocarbon product which acts as a crude or naphtha substitute), (2) solvolysis (solvolysis for depolymerizing PET via glycolysis, hydrolysis, and methanolysis, as well as solvolysis for PU, PA and PC among other plastics), (3) thermochemical depolymerization (conversion of plastic waste into a chemical-rich gas or monomers where specific chemicals (e.g. styrenes, BTX, methanol) can be recovered directly without the need for cracking or other downstream conversion processes), and (4) dissolution (solvents dissolve the target polymer, contaminants are then filtered out, and then the target polymer precipitated).

Some key highlights from the report are:

The period between 2024 and 2025 is a key inflection point for pyrolysis where we may see 1 Mtonne/y of completed global pyrolysis capacity – a sign of the tech’s commercial maturity.
Momentum in APAC is going strong, and we can expect a growth in the number of scale-up projects in the region. The EU may see a boost in large capacity scale-up commitments as its regulations on advanced recycling and mass balance begin to firm up.
The current announced capacity for dissolution shows little growth, but we predict that it will grow more quickly as tech developers are beginning to identify suitable applications.

Dr. Lee concludes that the projected growth in advanced recycling capacity bodes well for technology developers in general, and the growing venture capital funding trends share this optimistic outlook. While there are still some mixed signals from regional policies on advanced recycling technologies, especially pyrolysis, overall regulatory trends are not entirely adverse; advanced recycling technology adopters will likely still be able to operate viably albeit with some limitations (fuels exempted mass balance for recycled content attribution, for example).

For more information or to set up a call with Dr. Lee or one of our other analysts, please do not hesitate to reach out to us at [email protected] .

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