Peter Devreotes, the 2019 winner of ASCB’s E.B Wilson Medal, studies chemotaxis—how cells move in response to extracellular cues and attractants. In a way, chemotaxis mirrors Devreotes’ personal journey toward cell biology.
“In early grade school, my father, who was a mechanical engineer, would teach me math at home. So initially I was inspired by him. I still have his slide rules and drafting equipment,” Devreotes said. “Through high school and college, I was amazed at the discoveries of great physicists—early and modern. I am still impressed by the work of early electrophysiologists who brought rigorous theory to biological processes like membrane potential. I am also impressed by transformative breakthroughs such as green fluorescent protein (GFP) or single-molecule imaging in cell biology.”
Devreotes earned his BS in physics in 1971 at the University of Wisconsin, Madison, and then earned his PhD in biophysics in 1977 from Johns Hopkins University. After a Damon Runyon Fellowship at the University of Chicago, Devreotes returned to Johns Hopkins to join the faculty in 1980. He’s been the director of the Department of Cell Biology since 2000.
“When I look back it seems like I was on a predetermined course from physics through biophysics and biochemistry to cell biology,” said Devreotes, the Isaac Morris and Lucille Elizabeth Hay Professor of Cell Biology at the Johns Hopkins School of Medicine. “Really, at each point, I just switched to what seemed like the most exciting area. Right now, I think there is a great deal to learn about the behavior of molecular networks in cells. Discoveries in this area of cell biology will transform medicine.”
The Story of Chemotaxis
Nominated by several of his peers and colleagues, Devreotes’ scientific legacy thus far is telling the story of chemotaxis. Douglas Robinson, also a professor of cell biology at Johns Hopkins, wrote in his nomination letter, “Peter is incredibly deserving of this award as he has made several seminal discoveries in directed cell migration, has been a leader in bringing systems-level analysis to cell biology, and has been an active member of ASCB for many years.”
Robinson explained how Devreotes’ “attention to the dynamic interplay between the variety of cellular systems using clever experimental design and computational approaches sets chemotaxis on a higher plane of elegant understanding that researchers of other cellular processes aspire to.”
First, Devreotes identified how G-protein coupled receptors (GPCR) are involved in chemotaxis. Although these chemoattractant receptors, as well as their associated heterotrimeric G-proteins, are distributed uniformly around the cell surface, Devreotes was able to elucidate how the activation of GPCR produces phosphoinositides and causes asymmetric signaling. These signals are interpreted into the wavelike motion of the cell membrane, created by the alternating assembly and disassembly of the actin cytoskeleton. Lastly, Devreotes developed mathematical models for these systems.
“When I look back it seems like I was on a predetermined course from physics through biophysics and biochemistry to cell biology.”
Devoted to Dictyostelium
Throughout his career, Devreotes has used the amoeba Dictyostelium discoideum as his model organism.
“Dictyostelium is like an experimentally tractable immune cell. You can move quickly to learn fundamental mechanisms of chemotaxis, motility, cytokinesis, macropinocytosis, phagocytosis, and host-pathogen interactions,” he said. “These mechanisms are also shared with epithelial cells and fibroblasts. It is amazing how much this small community of researchers has contributed to knowledge of these processes. Other models such as Drosophila, zebrafish, etc., are better for understanding the complexity of development.”
Sticking with Dictyostelium for studies of motility and chemotaxis has sometimes proved to be challenging. “Despite its advantages, there is pressure from journals and funding agencies favoring studies in ‘relevant’ organisms. About half of the projects in the lab now are focused on human cells. But I must say that most of the new insights are still coming from Dictyostelium,” he said.
Basic questions in science still retain importance and value, despite a research landscape that seems to favor translational or clinical endeavors, he noted.
“One just has to look over a longer time period,” Devreotes said. “Most of the major technology and medical advances of today derive from curiosity-driven basic research. It is just short-sighted for funding agencies to be focused so strictly on translational research. Imagine if they made that decision in 1945 and stuck with it. We would have none of the miraculous diagnostics and treatments we have today.”
Cell Biology for the 21st Century
Devreotes said a good day in the lab is a day that uncovers new data that challenges old. “I think I am most excited about rigorous data that contradicts our current working model. I know we are about to move forward,” he said.
Devreotes said he thinks the behavior of molecular networks will be among the most important questions for future cell biologists because they could reveal potential therapies.
“Dictyostelium is like an experimentally tractable immune cell.”
“Cellular networks have internal feedback loops that confer excitable properties. I have had a fantastic time working with my friend control engineer Pablo Iglesias (also at Johns Hopkins), whose group brings computational simulation as a tool for understanding network behavior. I think that excitability controls many of the spontaneous behaviors that cells display,” he said. “Gene profiles and external cues influence behavior by altering these excitable properties. Currently, therapies target specific molecules, but in reality, these are altering network behavior. With a better understanding of networks, better interventions or combinations of interventions will be available.”
He said being a member of ASCB “has tremendously broadened my perspective. Serving on ASCB Council makes you proud to be part of the community and you feel that your contribution will help younger scientists.”
And as for younger scientists, his advice is simple. “Choose a big problem that you are passionate about, use imagination, and work hard to learn new truths about it. Try to tune out the peer pressure to publish in ‘elite’ journals and focus on results. Work together collaboratively with your colleagues,” he said.
What does the future hold for Peter Devreotes? “After 20 years, I am stepping down as Director of Cell Biology and I will devote more time to research. We still want to understand how cells sense and move toward directional cues.”
This will also give him more time to devote to outside passions. “I like biking, boating, fishing, being outdoors. My wife and I share hiking and birding. I am also interested in design. We recently designed and built an awesome house.”
Devreotes will present the 2019 E.B Wilson lecture on Tuesday, December 10, at 3:15 pm during the 2019 ASCB|EMBO Meeting in Washington, DC.
About the Author:
Mary Spiro is ASCB's Science Writer and Social Media Manager.