NOVO NORDISK FOUNDATION-SPONSORED VISITING SCHOLAR FELLOWSHIP RESEARCH PROJECT - 2017
Visiting Scholar: Jamin Hein (Novo Nordisk Foundation Center for Protein Research, University of Copenhagen)
Stanford Faculty Advisors: Martha Cyert (Biology) and Polly Fordyce (Genetics)
Using spectrally encoded peptide-based libraries to define the polo-like kinase 2 tumor suppressor role
Reversible phosphorylation of proteins is the most common mechanism of signal transduction in human cells, and the delicate balance between kinases and phosphatases creates dynamic regulatory networks. Communication within these signaling networks occurs through weak, regulated protein-protein interactions that are mediated by short amino acid sequences, or SLiMs, which occur in unstructured protein regions. Mapping human SLiM sequences is not only important for understanding biological processes, but also for discovering new drug targets. Jamin will use a combination of cell biology and biophysical methods to study the biological significance of SLiM-based interactions. Novel technologies are needed to study these interactions, which often have weak affinities, or depend on post-translational modifications. Jamin will use spectrally encoded peptide bead libraries to systematically and quantitatively map SLiM-domain interactions in the human proteome. Peptides will be synthesized on uniquely identifiable beads and can be modified, e.g. by phosphorylation. Using this approach, the interaction and binding affinities between any protein target and the peptide library can be analyzed in high throughput. This new method will decipher cellular information networks to reveal how cells make decisions, and how these decisions are hijacked during disease.