Biochemical Characterization of Endogenous GFP-BRAF
My research focuses on a kinase in the MAPK/ERK pathway called BRAF, which is commonly mutated in cancer. This summer, I will isolate BRAF endogenously from 293FT cells and analyze their structure by native mass spectrometry and cryo-electron microscopy. This strategy differs from most conventional approaches, as I will not overexpress the protein. Rather, I aim to study BRAF isolated from its native stoichiometric environment, circumventing assumptions that must be made with overexpression. With this strategy, I seek to learn about BRAFs activation and native binding interactions. This knowledge could inform anti-cancer drug discovery by revealing new structure-informed strategies to inhibit BRAF and gain greater control over MAPK/ERK regulation. Considering that past attempts of BRAF inhibition have had mixed results clinically within the current constraints of structural understanding, BRAF poses potential as a hopeful drug target that has yet to be harnessed. Furthermore, the endogenous tagging approach being refined in this project could be applied to other large signaling proteins, making it a valuable tool in the drug development pipeline.
Message to Sponsor
- Major: Molecular and Cell Biology
- Sponsor: Leadership Fund
- Mentor: Faculty Mentor: John Kuriyan, Graduate supervisor: Joseph Paul