Understanding evolution at the cellular level

By Krista McPherson

November 24 is Evolution Day, which commemorates Charles Darwin's work in evolution. In honor of that, we are featuring Michael Lynch, director of the Biodesign Center for Mechanisms of Evolution, and his work pioneering a new field of research, evolutionary cell biology.

“Evolutionary biology and cell biology are both highly sophisticated fields, but they have grown up with almost no contact, even though all things biological (including evolution) start at the cellular level,” said Michael Lynch, director of the Biodesign Center for Mechanisms of Evolution at Arizona State University. 

Under Lynch’s leadership, the center is working to change that, unlocking a new wave of discoveries in a budding sector of science, evolutionary cell biology.  

In 2021, the National Science Foundation awarded ASU a $12.5 million grant to build the Biological Integration Institute for Mechanisms of Cellular Evolution, housed within the center. With an emphasis in interdisciplinary research beyond biology, that funding has helped the center grow from a single lab to around 100 participants within ASU and outside collaborations, both domestically and internationally.  

In addition to expanding the foundation of science, Lynch is training the next generation of scientists and researchers. All of the research done in his center is run by grad students and postdoctoral researchers, as well as a sizable amount of undergraduate students, to explore the world of genetics and evolution.  

“We do everything possible to encourage their creativity and to manage things in a way that maximizes their career potential,” said Lynch. As much as students learn from Lynch, he too learns new perspectives and information from working with students from different disciplines and colleagues across the Biodesign Institute.  

Below, Lynch talks about the science in the center and his own background and inspiration. Answers are edited for length and clarity.  

Question:  What is the research focus of your center? 

Answer: We are developing a new field of evolutionary cell biology, attempting to understand how cells alter their structures and functions via genetic changes, and how various lineages of organisms are constrained in different ways. Our focus is specifically at the molecular level, especially on single-celled species, which constitute the vast majority of organisms on the planet (both in terms of numbers and biomass). Integrating data with mathematical theory, we are attempting to develop a comprehensive view of the mechanisms by which evolution proceeds. 

Q: Why is this work important to society? 

A: The cell is the unit of all of life, and hence where an organism’s success and failure begins. Many of the current threats of human society are evolutionary in nature, such as the emergence of novel pathogens, the threats to agriculture and natural systems from invasive species, the proliferation of cancerous mutant cells in the human body and the ability to adapt to global warming.  

Q: What is the biggest challenge in this field of research? 

A: Two of the major challenges in evolutionary biology are connecting genomic changes arising by mutation with the downstream phenotypic changes and developing mathematical laws to help understand such links. Another major challenge is to understand the extent to which evolution is guided by natural selection alone, as opposed to being driven by mutational forces and chance variation. The major limitation here is intellectual in nature — evolutionary biology and cell biology are both highly sophisticated fields, but have grown up with almost no contact, even though all things biological (including evolution) start at the cellular level. We are trying to build a novel center that breaks down these barriers.  

Q: If someone gave your center $100 million, what would you do with it? 

A: Two things. First, I would develop a state-of-the-art facility so that our insight into cells is minimally constrained by technical limitations and major financial constraints that come with things like genome sequencing and proteomic costs. This would include not just fancy machinery, but also highly trained research scientists to guide their implementation. We really are limited financially with respect to the mass of data that we require to understand evolution; sample sizes are currently far too small to make the kind of inferences that we’d like (owing, among other things, to the rarity of mutations). 

Second, I would establish one or more “evolutionary observatories,” where long-term studies could be performed on the suite of natural populations of interacting species, possibly even having replicated microcosms that would allow controlled experiments. One of the most pressing problems now facing humanity is global warming — what types of species are most likely to proliferate or decline towards extinction with a specified temperature increase?  

Q: Can you talk about research in your lab that aligns with Biodesign’s nature-inspired research? 

A: We are specifically focused on how the design of organisms comes about, and the degree to which this is adaptive or nonadaptive. How close has natural selection brought traits to the maximum possible level of perfection? Where can improvements be made? What are the weak links that might be capitalized on in management programs, such as the eradication of pests and pathogens?  

Q: How did you become interested in science, and in particular, the field you are in? 

A: I started out in ecology as a graduate student and eventually wove my way to evolutionary biology after starting as a faculty member, a field where it becomes possible to establish the big picture of the tree of life, where it came from and where it might go. And to do so by integrating predictive and explanatory mathematical theory with detailed observations at the molecular and cellular level. 

Q: What key events set you on your research path? 

A: A lot of serendipity. I went to a small undergraduate institution, and nearly headed off to medical school, but learned about a thing called research in my final year. I then got lucky by having gained acceptance into one of the best programs in the country at the time. From there, I went immediately into my first faculty position, focused on the biology and ecology of lakes, but then became intensely interested in genetics and evolution. As the latter fields became more and more mathematical and molecular, I was positioned to capitalize on my various backgrounds to try to pull things together.   

Q: What is the most fun aspect of your work in the center? 

A: I enormously enjoy building bridges between different areas of science, and the center is an unconventional group, uniquely positioned to do just that. In some sense, the field of evolutionary biology has become a bit stagnant, as it has failed to make the links between other key branches of the life sciences. Cell biology is the last great frontier, which is precisely where the center is focused. In addition, few things give me more pleasure than helping our graduate students and postdocs fulfill their career aspirations. 

Q: What is your favorite thing about working at Biodesign? 

A: It provides both a physical and intellectual setting that helps make all this possible, and the new faculty that I’ve been able to hire are great colleagues. We’ll now see if we can put everything together. 

Q: Has your teaching and mentorship helped inform your research, and if so, in what ways? 

A: There is no better way to understand a subject and where the key unknowns lie than to teach a course in the area. I try to integrate ideas from a lot of different areas — a luxury that comes with age and the cumulative time that allows such breadth — and teaching helps crystallize things. I’ve also been lucky to have a lot of creative and motivated graduate students, sometimes bringing in new areas of expertise into the lab. That’s an ideal situation in my opinion, as sort of mutualistic, joint mentoring goes on.