Researcher: Dr. Sangita Sinha
Project Title: Investigating Beclin 1 structure
Autophagy, a conserved, catabolic eukaryotic pathway is essential for cellular homeostasis. Beclin 1 is a key conserved autophagy effector, but the mechanism by which it mediates autophagy is unknown. Our central hypothesis is that Beclin 1 is an interaction hub for autophagy, with various competing interactions either facilitating or inhibiting autophagy. The goal of this proposal is to investigate the structure and function of an uncharacterized Beclin 1 N-terminal region; establish the structure and conformation of multi-domain Beclin 1 constructs in the basal autophagy-inactive state; probe conformational changes upon binding of the autophagy inhibitor, Bcl-2; investigate how these different interactions compete with or complement each other; and investigate the role of highly conserved Beclin 1 residues in autophagy. This work will provide invaluable information about Beclin 1 structure, conformation and oligomerization, and elucidate how selected interactions modulate Beclin 1 structure and function. Pending funding of an R01 proposal, funds from this CoBRE Pilot proposal will support ongoing work and publication of our substantial results.