Assistant Professor of Chemistry
Ph.D. Stanford University, 2008
(Biological Chemistry, Enzymology)
The Zalatan research group seeks to understand the molecular mechanisms that allow living cells to process, integrate, and coordinate signals. Cells use complex networks of proteins to respond to signals, and these networks must be regulated to ensure that specific reactions occur at the right place and at the right time. We focus on individual reaction steps at key decision points in cell signaling pathways, using a wide range of tools from biochemistry, enzymology, and synthetic biology. This approach allows us to draw connections between molecular events and cellular behaviors, providing a framework to identify new drug targets and to engineer synthetic pathways for cell-based therapeutics and devices.
Current projects are focused on the role of scaffold proteins that physically organize signaling networks. Scaffold proteins can facilitate signaling by directing signals to the correct target and preventing off-target reactions. Outstanding challenges for the field are to understand, at a molecular level, how scaffold proteins accelerate signaling reactions and how scaffold proteins themselves are regulated to direct signals. Addressing these questions allows us to engineer designer scaffolds to control biological pathways.
Zalatan, J. G.; Lee, M. E.; Almeida, R.; Gilbert, L. A.; Whitehead, E. H.; La Russa, M.; Tsai, J. C.; Weissman, J. S.; Dueber, J. E.; Qi, L. S.; Lim, W. A. "Engineering Complex Synthetic Transcriptional Programs with CRISPR RNA Scaffolds." Cell 2015, 160, 339-350.
Zalatan, J.G.,* Coyle, S.M.*, Rajan, S., Sidhu, S.S., Lim, W.A. "Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation.” Science 2012, 337, 1218-1222.
Lassila, J.K.,* Zalatan, J.G.,* Herschlag D. “Biological phosphoryl-transfer reactions: Understanding mechanism and catalysis.” Annu. Rev. Biochem. 2011, 80, 669-702.
Zalatan, J.G., Fenn, T.D., Herschlag, D. “Comparative enzymology in the alkaline phosphatase superfamily to determine the catalytic role of an active site metal ion.” J. Mol. Biol. 2008, 384, 1174-1189.
Zalatan, J.G., Fenn, T.D., Brunger, A.T., Herschlag, D. “Structural and functional comparisons of nucleotide pyrophosphatase/phosphodiesterase and alkaline phosphatase: Implications for mechanism and evolution.” Biochemistry 2006, 45, 9788-9803.
Zalatan, J.G., and Herschlag, D. “Alkaline phosphatase mono- and diesterase reactions: Comparative transition state analysis.” J. Am. Chem. Soc. 2006, 128, 1293-1303.