EM Core Voucher Award 2023: David Rodgers

Institution: University of Kentucky

Department: Molecular and Cellular Biochemistry

Rank: Associate Professor

Project Title: Insulin degrading enzyme in edosomal compartments and its role in the degradation of insulin and amyloid beta

About the project: Insulin-degrading enzyme (IDE) is a primarily cytosolic peptidase important in the degradation of insulin, the amyloid beta peptide (and other bioactive peptides) that plays important roles in type 2 diabetes and Alzheimer’s disease pathophysiology. IDE therefore is a potential target for drugs to treat these diseases. We are trying to understand how IDE encounters its substrates in a subcellular endosomal compartment, which may provide a new avenue for therapeutic intervention.

How funding from KY INBRE helps accomplish these goals: We propose to use the UK Electron Microscopy Core TEM and associated facilities to (1) interrogate endosomal surface association versus endosomal uptake of IDE, (2) characterize IDE association with different endosomal compartments, and (3) determine proximity of IDE with insulin and amyloid-beta in the endosomal system.

Intended outcomes: Our findings could uncover a novel mechanism of substrate degradation by IDE in recycling endosomes.