Assistant Professor of Chemistry
Ph.D. Stanford University, 2008
(Biological Chemistry, Enzymology)
The Zalatan research group studies the molecular mechanisms that allow living cells to process, integrate, and coordinate signals. We are interested in understanding how complex and interconnected signaling pathways are organized to direct signals to specific outputs. We focus on individual reaction steps at key decision points in signaling networks, using a wide range of tools from biochemistry, enzymology, synthetic biology, and cell biology. This approach allows us to draw connections between molecular events and cellular behaviors, providing a framework to identify new therapeutic targets and to engineer synthetic pathways for cell-based therapeutics and devices.
Current projects focus 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 will allow us to engineer designer scaffolds to control biological pathways.
We are also interested in the organization of metabolic pathways. We have developed new tools to synthetically rewire gene expression programs, and we are applying these tools to understand how chemical precursors are routed through metabolic networks. This approach will enable us to engineer these pathways for small molecule biosynthesis.
Gavagan, M.*, Fagnan, E.*, Speltz, E.B., Zalatan, J.G. The scaffold protein Axin promotes signaling specificity within the Wnt pathway by suppressing competing kinase reactions. Cell Systems 2020, 10, 515–525.
Speltz, E.B., Zalatan, J.G. The relationship between effective molarity and affinity governs rate enhancements in tethered kinase-substrate reactions. Biochemistry 2020, 59, 2182–2193.
Fontana, J.*, Dong, C.*, Kiattisewee, C., Chavali, V.P., Tickman, B.I., Carothers, J.M., Zalatan, J.G. Effective CRISPRa-mediated control of gene expression in bacteria must overcome stringent target site requirements. Nat. Commun. 2020, 11, 1618 (11 pp.).
Dong, C., Fontana, J., Patel, A., Carothers, J.M., Zalatan, J.G. Synthetic CRISPR-Cas Gene Activators for Transcriptional Reprogramming in Bacteria. Nat. Commun. 2018, 9, 2489 (11 pp.).
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.
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.