Maximizing Investigators' Research Award

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ABSTRACT My lab has two main areas of interest: 1) tail-anchored (TA) protein targeting and quality control; 2) selective autophagy. Given that selective autophagy targets toxic protein aggregates and damaged organelles for destruction, these two research areas have strong conceptual ties. In many cases we are answering similar questions about substrate selectivity: What distinguishes newly-synthesized TA proteins as substrates for endoplasmic reticulum protein targeting from TA proteins targeted to mitochondria? What distinguishes TA proteins that are mistargeted to mitochondria as quality control substrates from native mitochondrial TA proteins? What distinguishes apparently damaged organelles as selective autophagy substrates from healthy organelles? To answer these questions, we are dissecting diverse molecular mechanisms that select substrates of grossly different sizes and operate on very different time scales. My lab is known for its biochemical reconstitution work in the budding yeast S. cerevisiae but more recently we have done genomics, quantitative yeast cell microscopy with theoretical modeling, and genome-wide screens in mammalian cells.