The role of electricity in biology has been a longstanding subject of fascination, with common understanding that action potentials generated by the movement of electrically charged ions across nerve cell membranes is how nerves work. But our popular understanding of electricity in biology has stalled, somewhat, at nerves. What is less common knowledge is that ions are trafficked across the membranes of all cells: all cells have an electrochemical gradient. More interestingly, bioelectric potentials and bioelectrical communication among cells are increasingly thought to be responsible for the different shapes that living systems have, known as morphogenesis.
One of the ways in which this bioelectric potential is achieved is by the distribution of positively charged protons across a membrane, through the action of V-ATPase proton pumps. These V-ATPase proton pumps have mostly been known for their roles in acidifying various intracellular membranes, but are now implicated as cell-surface regulators of voltage potential that drives several aspects of large-scale anatomical control, including the regeneration of appendages as well as the growth of cancer cells.
The Guy Foundation is delighted to announce that it has awarded a grant of $290,778 towards understanding the way in which V-ATPase function might be linked to whole body form. The project is being undertaken by Professor Mike Levin at Tufts University and Professor Wayne Frasch at Arizona State University. Professor Levin suggests that “birth defects, traumatic injury, and other dysregulations of body anatomy such as aging and cancer could all be addressed if we solved one major open problem: how to control which complex structures cells will build”. Advances made by the Levin lab and collaborators have recently involved the development of a Xenobot. Xenobots are proto-organisms that self-assemble from isolated groups of skin cells. While they are capable of motion and display individual as well as group behaviours, they are simple and tractable enough to be ideal organisms with which to investigate bioelectricity and the related role of V-ATPase in enabling cells to cooperate toward these novel functional forms. Professor Wayne Frasch, leader of
The Biomedicine and Biotechnology Faculty at Arizona State University and an expert on ATPase and its different isoforms said, “The V-ATPases are not only a major contributor to cellular membrane potential, but they are highly regulated by a network of sensors that respond to the availability of metabolites needed for cellular growth and differentiation. Genetic mutations of these proton pumps are associated with devastating diseases and cancer. As a result, they are a likely driver of organismal development”.
The project is one that is close to Guy Foundation Founder and Chairman, Professor Geoffrey Guy’s interests. He remarked “The Foundation has always had an interest in how bioenergetics may play a role in the way in which information is propagated across living systems. I am delighted to say the Foundation played a key role in thinking up the notion behind this project, through contributing to the interaction and cross-talk between cutting-edge scientists in our online lectures, which advance beyond the confines of engrained thinking and consider profound questions at the nexus of physics and biology. Fascinated by the question of bioelectricity and ATPase function in one such lecture session, we instigated discussions with Professor Levin and Professor Frasch and our team were instrumental in shaping this collaborative research project. We are intrigued to see whether the energetics of the V-ATPase proton pump influence morphogenetic information in living organisms and how this might be leveraged towards new therapeutics”.