Sanjib DuttaEducationPh.D. University of Rochester, NY (2006) ResearchI am interested in studying specificity of interactions between proteins of the Bcl-2 family that are involved in apoptosis. Specifically I am studying interactions between a specific class of pro-apoptotic proteins (BH3 only) and different members of the family of anti-apoptotic proteins. Interactions between these two classes of proteins are critical in deciding the cell fate and overexpression of antiapoptotic proteins is a common characteristic in many tumor cells. This interaction is mediated by binding of an amphipathic helix from the BH3 only proteins to a hydrophobic groove in the anti-apoptotic proteins. BH3 peptides corresponding to the helical segments have been widely used to understand the molecular determinants of specificity. To address this issue I have used a library screening approach to isolate BH3 peptides specific for anti-apoptotic proteins. Using yeast surface display and a selection approach combining postitive and negative selection I have identified peptides targeting two anti-apoptotic proteins specifically. Besides understanding the important question of specificity I am also interested in testing these engineered peptides as reagents for in vivo applications to understand the complex biology of the Bcl-2 family of proteins PublicationsDutta S, Gullá S, Chen TS, Fire E, Grant RA, Keating AE. (2010) Determinants of BH3 binding specificity for Mcl-1 versus Bcl-xL. Journal of Molecular Biology, 398(5):747-62. Dutta S., Koide A., Koide S. (2008) High-throughput analysis of the protein sequence-stability landscape using a quantitative yeast surface two-hybrid system and fragment reconstitution. Journal of Molecular Biology, 382(3):721-33. Dutta S.*, Batori V.*, Koide A., Koide S. (2005) High- affinity fragment complementation of a Fibronectin Type III domain and its application to stability enhancement. Protein Science, 14(11):2838-48.[*both authros contributed equally to this work]. CollaboratorsEmiko Fire, Stefano Gulla, Tsan Chou, Scott Chen |