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Abstract:
Small molecules play critical roles in human health. While we appreciate their unique capabilities as drugs, the body’s natural small molecules– metabolites– remain the least understood aspect of our physiology. Our lab seeks to illuminate how Nature encodes biological information in metabolite structure. In this seminar, I’ll introduce the chemoproteomic technology we’ve developed to profile protein targets of oxysterol metabolites in cells, and show how it’s revealed an orphan receptor that directly links
neuropsychiatric disorders to cholesterol metabolism. In the second part of my talk, I’ll discuss how we’ve used chemical and biological tools to illuminate the mechanism of Hedgehog protein autocholesterolysis. By mapping the reactivity of this protein to the topology of its cholesterol binding site, I’ll demonstrate how we’re repurposing Hedgehog for genetically encoded protein modification in cells. Throughout, I’ll show how we use the lens of chemistry to decode molecular information in living systems.