Lysosomes are ubiquitous cellular compartments with well-characterized roles in the degradation and turnover of cellular components. Lysosomes function in a diverse array of important cellular processes including the presentation of antigens to the immune system, the turnover of cell surface signaling molecules, tissue remodeling, and the destruction of pathogens. While much is known regarding the cellular and biochemical function of lysosomes, the processes involved in lysosome assembly and maintenance in multicellular animals remain poorly understood. To aid in the understanding of these processes, the Hermann lab has begun to identify genes necessary for the assembly/stability of lysosomes in the intestinal cells of the model multicellular organism, C. elegans. One of the genes identified, glo-1, encodes a Rab GTPase that may regulate transport between cellular compartments. This work aims to determine whether glo-1 functions in the assembly or the maintenance of lysosomes and if glo-1 prevents the inappropriate fusion of lysosomes with the cell membrane. To learn which step in lysosome assembly/stability requires GLO-1 protein function, this research will determine the sub-cellular localization of GLO-1. Finally, this project will extend the pilot genetic screen that led to the identification of glo-1 to identify additional genes that are necessary for lysosome assembly/maintenance. This research will identify and characterize the activity of genes that are likely to function in the assembly/maintenance of lysosomes in all multicellular animals. Regulation of lysosome content effectively prevents the accumulation of dysfunctional proteins and organelles in cells. The project is being conducted at an undergraduate insitution, and large numbers of undergraduate students will receive training in research as part of their formal course work and in independent research projects.
