The University of Texas Southwestern Medical Center received a $300,000 Project Grant from the National Institute of General Medical Sciences' Biomedical Research and Research Training program to support research on the biophysical study of endoplasmic reticulum (ER) protein recognition for degradation and lipid homeostasis. The award period is from April 1, 2021 through March 31, 2022.
The grant will fund research to elucidate the molecular and biophysical mechanisms underlying the targeted degradation of proteins involved in cholesterol and sphingolipid metabolism pathways. This will include determining the structure of sterol regulatory element-binding protein 2 (SREBP2) in complex with its chaperone SREBP cleavage-activating protein (SCAP) using cryo-electron microscopy techniques. Additionally, the researcher will characterize the interaction between SREBP2 and ER-resident E3 ubiquitin ligase TRC8 and how this is modulated by SREBP2-SCAP binding. The grant also supports establishing an independent research program to study how degradation regulates sphingolipid levels via the interaction between serine palmitoyltransferase and its regulatory proteins ORMDL1-3.
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