RUI-Investigating the Mechanism of GLO-1 Rab Function in C. Elegans Lysosome-related Organelle Biogenesis

Lewis And Clark College, Portland OR

Investigators

Abstract

Intellectual Merit: The cells of complex organisms contain a diverse array of discrete functional units called organelles. These compartments carry out essential cell activities and are broadly conserved within and between species. Lysosomes, one type of organelle found within nearly all plant and animal cells, function as major sites of degradation. Interestingly, in many cell types, lysosome-related organelles (LROs) co-exist with conventional degradative lysosomes due to the activity of specific pathways mediating the formation of LROs. However, most of the known factors that mediate LRO formation also function in the construction of lysosomes, raising the question of what controls the specific formation of LROs. A family of homologous Rab proteins, which generally act as switches to regulate the processes involved in moving material between organelles, have been identified that function in the formation of LROs but not conventional lysosomes. This project explores the hypothesis that these Rabs control LRO-specific formation processes by investigating the activity of the GLO-1 Rab protein that functions in the construction of an LRO called the gut granule. Gut granules are found within the intestinal cells of the model genetic organism C. elegans and are analogous to organelles in mammals that function in the synthesis/storage of substances mediating pigmentation and blood clotting. Briefly, the research will identify the cellular site of GLO-1 function, the regulators of GLO-1 activity, and the processes controlled by GLO-1. As GLO-1 is highly conserved, this research will provide important insights into the mechanisms mediating the formation of LROs in a diverse array of cells and organisms. Broader impacts: The research will involve 30 undergraduates a year in collaborative, investigative, and original research. Undergraduate students working in the PI's research laboratory and upper division Cell Biology course (enrollment 24) will design, implement, interpret, and present the results of their experiments investigating the function of GLO-1 in LRO formation. The PI will participate in HHMI and Miller Foundation supported initiatives at Lewis & Clark College to increase the representation of underrepresented groups in science by mentoring the studies of LRO formation by local high school and community college students in the research lab. Ultimately, this work will provide hands on scientific training for a large and diverse array of students, many of whom will progress on to careers in research and education