SNARE function and phosphoinositide induced conformational and oligomeric changes

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

Cellular communication is important for a multitude of physiological processes. Organelles are membrane bound structures within the cell that communicate through the transport and fusing of materials in vesicles. Many proteins control fusion, yet the role of the membrane itself remains unclear. Membranes contain specialized lipids, and it is known that altering these lipids will negatively impact vesicle fusion; however, the mechanism of this is unknown. The investigator will study how lipids affect protein function during fusion to paint a better picture of this process. The Broader Impact activities include training of scientists at all levels. In addition, the investigator is also a member of the Boy Scouts of America and will serve as a merit badge counselor for Chemistry, Nuclear Science, and Public Health where he hopes to spark a life-long curiosity in science. Eukaryotes rely on membrane fusion to maintain cellular homeostasis, including processes such as exocytosis, endocytosis, and exosome release, making it imperative to understand the processes that make membrane fusion possible. SNARE proteins are critical in the membrane fusion process and in this project, the investigator seeks to understand how SNARE proteins drive membrane fusion. This project focuses on the SNARE protein Vam7, which is known to trigger vesicle fusion; however, Vam7’s regulation by the lipid environment is unclear. The investigator will use biochemical and biophysical approaches to understand how membrane lipids interact with Vam7 domains, elucidate how lipid binding induces Vam7 conformational changes and multimerization, and investigate how Vam7 lipid binding and multimerization can affect different stages of macroautophagy. The completion of this project will define the how Vam7 is regulated by the membrane to promote fusion. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.