Molecular Mechanisms of Lysosome Biogenesis

University Of Arizona, Tucson AZ

Investigators

Abstract

INTELLECTUAL MERIT The aim of this project is to decipher mechanisms of lysosome biogenesis. Lysosomes are the main membrane-bound, degradative organelles of eukaryotic cells. In addition to degrading endocytosed molecules from the extracellular medium, lysosomes regulate multiple essential cellular processes, including degrading material for turnover of cellular organelles, degrading material to respond to starvation, degrading signaling receptors to regulate developmental pathways, fusing with the plasma membrane to initiate wound healing, and mediating some cell death pathways. Given this central importance of lysosomes, it is striking that little is known about basic principles of how lysosomes are formed, the process of lysosome biogenesis. Fundamental to the understanding of how lysosome biogenesis is regulated requires identifying the proteins that function in this process. The aim of this project is to characterize six novel proteins that were identified as regulators of lysosome biogenesis. Using sophisticated genetic and cell biological tests in the C. elegans model system, this project will determine how these proteins interact to modulate the dynamic membrane events required to form a new lysosome. These approaches are likely to provide mechanistic molecular insight into lysosome biogenesis. BROADER IMPACTS First, this project will transform current views of membrane transport by establishing a molecular model of lysosome biogenesis. Second, this research program will continue to support a strong training mission in undergraduate student research. The P.I. has a strong record of undergraduate training, particularly with students from under-represented groups. The majority of these students eventually enter into graduate programs and pursue a career in science. Most of students that will be trained on the present project will be encouraged to present their work at research conferences and will be authors on peer-reviewed publications emerging from the work. This research program will serve as a platform for the scientific development of the next generations of scientists and health professionals.