Cellular and Genetic Analysis of Lysosome and Lysosome-Related Organelle Biogenesis in C. Elegans

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Lysosomes are membrane bound compartments found in nearly all animal cells that have well characterized roles in the degradation of intra and extra-cellular derived material. While much has been learned regarding the diverse and important processes that lysosomes carry out in cells, the mechanisms underlying the assembly of lysosomes in complex multicellular animals, especially as they develop during embryogenesis, are relatively unstudied. To aid in understanding of these processes, Dr. Hermann is identifying and characterizing genes necessary for the assembly of lysosomes in the embryonic intestine of the model multicellular organism C. elegans. The Hermann lab has identified gut granules as a cell type specific, lysosome-related organelle that functions in the storage of fat. To gain detailed insight into the mechanisms controlling the formation of gut granules the Hermann lab has isolated and is characterizing a collection of glo mutants that are defective in gut granule biogenesis. Most genes identified to date that function in the biogenesis of lysosome-related organelles are not required for embryonic viability. The Hermann lab has identified 22 embryonic lethal glo mutants that extracellularly mislocalize gut granule contents. The genes necessary for the formation of gut granules whose activity is disrupted in these strains will be molecularly identified. Studies of these genes are likely to provide novel insights into the pathways necessary for lysosome biogenesis in multicellular organisms. Recent studies in C. elegans suggest that yolk platelets and LMP-1::GFP containing compartments in the intestinal primordium also represent lysosome-related organelles. Whether LMP-1::GFP containing organelles, yolk platelets, and gut granules have characteristics of conventional lysosomes, other endosomal compartments, or each other will be investigated using microscopic and genetic approaches. If these three compartments represent distinct lysosome-related organelles, the embryonic intestine would provide a powerful genetic system to investigate how structurally and functionally distinct lysosomal compartments are formed in the same cell.The project will involve 25 to 30 undergraduates a year in independent, hands-on, original research. Undergraduate students working in the PI's lab and upper division Cell Biology course (enrollment 24) will carry out the studies. The work will provide molecular insights into the assembly of lysosomes likely to be conserved in the assembly/maintenance of lysosomes in all multicellular animals.