The focus of my research is to understand the molecular mechanisms that affect the cellular process of autophagy, and how autophagy is regulated in multicellular organisms. Autophagy is the major cellular pathway for degrading long-lived proteins and cytoplasmic organelles. It involves the rearrangement of subcellular membranes to sequester cargo for delivery to the lysosome where sequestered material is degraded and recycled. Recent studies have implicated a direct role for autophagy in the aging process of multicellular organisms, including the nematode C. elegans. In this organism, several conserved longevity pathways and processes are known to affect lifespan, including insulin/IGF-1 signaling, food intake (also referred to as dietary restriction), protein translation and mitochondrial respiration. Interestingly, mutants with reduced insulin/IGF-1 signaling and dietary-restricted animals have elevated levels of autophagy and require genes involved in autophagy to live long.
We use a combination of genetic, molecular and cellular biological approaches in the genetically tractable model organism C. elegans. In particular, our lab aims to: 1) determine the role of autophagy genes in development, aging, and fat accumulation; 2) understand the mechanism(s) by which autophagy extends lifespan; 3) identify new evolutionarily conserved genes that regulate autophagy; and 4) address whether the autophagy function of such novel genes is conserved in other animals. We began our characterization of autophagy genes by studying bec-1 in C. elegans. Its human homolog, beclin 1 was identified as the first autophagy gene in humans and shown to be monoallelically deleted in up to 75% of various human cancers. Therefore, any insights on the function of bec-1 is likely to advance our molecular understanding of important signaling pathways relevant to aging, and age-related disorders, including diabetes and cancer.