CSDE1 as a Post-Transcriptional Regulator of the LDL Receptor
John Chorba, Professor
UC San Francisco
Applications for Fall 2024 are closed for this project.
The LDL receptor clears atherogenic LDL particles from the bloodstream and plays a major role in cholesterol and membrane homeostasis. Through a genome-wide CRISPR interference screen, we identified novel regulators of the LDL receptor as potential therapeutic targets for cholesterol lowering. We have shown that CSDE1 is an RNA-binding protein that mediates LDLR mRNA decay in liver cells and validated both its effects and a proof-of-concept for therapeutic targeting in vivo. We aim to understand the mechanistic and structural details of this new player in LDL receptor regulation and prosecute it as a therapeutic target.
Qualifications: Key laboratory tasks can include:
- Cloning and expression of engineered proteins
- Generation of CRISPR knockout cell lines
- Flow cytometry evaluation of surface receptor expression levels
- RNA extraction and quantitative PCR
- Pulldown and affinity purifications of target proteins
- Mass spectrometry analysis of protein targets
- Generation of RNA libraries and deep sequencing
- In vivo models of CSDE1 perturbation, along with assessment of atherosclerosis and lipid metabolism phenotypes
The student will work collaboratively with the lab to develop gradually increasing levels of independence to identify a sub-project of which they can take ownership.
Hours: to be negotiated
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Biological & Health Sciences