The trafficking of macromolecules between different compartments is an essential process in all eukaryotic cells and is used to maintain cellular integrity, to interact with the extracellular environment, and to generally modulate various cellular activities. Numerous advances have been made in understanding different pathways of membrane trafficking and in elucidating some of the factors that regulate them; these advances have demonstrated a striking conservation of these pathways among all eukaryotic cells.
We are studying membrane trafficking, focusing on lysosomal transport, using primarily the nematode Caenorhabditis elegans as a model system. We are also using mouse macrophages as a parallel system that complements the genetic studies we carry out in C. elegans. Current projects in the laboratory are:
1) Elucidating mechanisms of lysosome biogenesis, starting with CUP-5 in C. elegans and its mammalian ortholog TRPML1. Mutations in MCOLN1, the gene that encodes TRPML1, results in the lysosome storage disorder Mucolipidosis type IV.
2) Defining the basis for the lysosomal and cell death phenotypes in the absence of CUP-5. We identified several suppressors of cup-5 mutant defects. The analysis of these suppressors will identify the molecular events that exacerbate cup-5 mutant phenotypes. These suppressors also constitute leads towards identifying treatments for Mucolipidosis type IV.