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Drosophila sensory neurons tile the larval body wall, Dr. Chun Han


Sandler Building, Room 310A Box 0518
(415) 502-3775

Daniel Southworth

Structure/function of heat shock proteins and protein quality control

In the crowded cellular environment, processes that coordinate the folding, assembly and clearance of proteins are fundamental to cellular function and stress response. Malfunction leads to toxic protein aggregation, abnormal cell growth and the progression of many diseases including cardiovascular and neurodegenerative diseases, and cancer. Our lab is focused on elucidating the structure and function of dynamic molecular chaperone machines that are essential for maintaining the integrity of the cellular proteome. We utilize the latest techniques in single particle cryo-electron microscopy (cryo-EM) to determine 2D and 3D molecular snapshots and structural models. Our emphasis is on understanding the dynamic, often nucleotide-dependent conformational changes and client-substrate interactions that underpin chaperone network function; these complex interactions are a tremendous challenge to structural biology approaches. Thus, our cryo-EM efforts are coupled to powerful biochemical approaches including in vitro assembly methods, functional analyses and chemical crosslinking approaches to define and capture relevant, functional states. With this focus we aim to uncover fundamental mechanisms of proteostasis that can be targeted in therapeutic approaches to prevent protein folding diseases.