Special Seminar: Exploring and Engineering Protein Conformational Space via Single-Molecule Deep Sequencing of Polypeptides

ZOOM LINK
Meeting ID: 977 7792 8244
Passcode: 813105

Non-native protein conformations drive misfolding diseases, complicate protein engineering, and fuel molecular evolution. These conformations have remained largely intractable to experimental investigation. How to map a given protein’s full conformational space, in vitro and in vivo? How to determine each conformer’s consequences for the protein’s function or the organism’s fate? And how to mold this conformational landscape for biomedical purposes, like new antimicrobials or anti-misfolding vaccines?

I will first share a specific example of how a disulfide-trapped non-native protein conformation can lead to loss of vision due to cataracts, and how the eye has evolved to resist it. I will then describe a new technology for revealing protein conformation-phenotype relationships via “deep” disulfide scanning and highlight the importance of single-molecule protein sequencing for this capability.

About the Speaker(s)

Eugene Serebryany
Postdoctoral Fellow, Chemistry & Chemical Biology, Harvard

Serebryany is currently an NIH K99/R00 postdoctoral fellow in the Shakhnovich lab in the Department of Chemistry and Chemical Biology at Harvard. His focus is on discovering biological consequences of non-native protein conformations. During his PhD work with Jonathan King at MIT biology, he elucidated a surprising molecular mechanism of cataract formation and proposed a safe and simple therapeutic strategy for this highly prevalent disease whose only current treatment is surgery. He went on to invent high-throughput disulfide scanning (HTDS) as a way to advance both fundamental and applied research on sequence-conformation-phenotype relationships in proteins.

Contact

For more information, contact Ashley Parker at ashley.l.parker@dartmouth.edu.