Mark Goulian

Edmund J. and Louise W. Kahn Endowed Term Associate Professor of Biology

Ph. D. Harvard University, 1990.

204F Carolyn Lynch Laboratory
Department of Biology
University of Pennsylvania
Philadelphia, PA 19104 USA

V	+1 215 573.6991
F	+1 215 898.8780
E	goulian@sas.upenn.edu

two-component signaling in E. coli. regulation of porin expression, directed evolution of signaling circuits

Our research is focused on two-component signaling in bacteria. Two-component systems are regulatory circuits that mediate responses to diverse environmental signals and play a central role in regulating many aspects of bacterial physiology. At the simplest level, these circuits are composed of an upstream sensor kinase and a downstream response regulator. The response regulator is usually a transcription factor, although in some instances it controls other cellular processes such as protein degradation, protein localization, or flagellar motor switching. Depending on the circuit, additional phospho-transfer steps or additional regulatory proteins may be involved in the signal transduction process. Two-component systems provide an excellent context in which to study cell signaling. These systems tend to be relatively simple, with a small number of components; they can be found in genetically tractable, well-studied organisms; and there are many examples of such systems that can be used for comparing and contrasting designs (E. coli K-12 alone contains roughly 30 two-component systems). Our research applies techniques from genetics, molecular biology, fluorescence microscopy, and mathematical modeling to explore the design principles underlying two-component systems. We have been particularly interested in the mechanisms that maintain fidelity in transducing and processing signals. We are developing new techniques to measure signaling activity, both across populations and at the level of the single cell, in order to formulate and test quantitative models. We are also engineering networks within E. coli in order to build novel circuits and to explore the general design constraints and schemes for cell signaling.

selected publications

Derr, P., E. Boder, and M. Goulian. 2006. Changing the Specificity of a Bacterial Chemoreceptor. J. Mol. Biol. 355:923-932.

Goulian, M. and M. van der Woude. 2006. A Simple System for Converting lacZ to gfp Reporter Fusions in Diverse Bacteria. Gene 372:219-226.

Batchelor, E. and M. Goulian. 2006. Imaging OmpR Localization in E. coli. Mol. Micro. 59:1767-1778.

Batchelor, E., D. Walthers, L.J. Kenney and M. Goulian. 2005. The Escherichia coli CpxA-CpxR Envelope Stress Response System Regulates Expression of the Porins OmpF and OmpC. J. Bacteriol. 187:5723-5731.

Vijayan, K. D. Discher, J. Lal, P. Janmey and M. Goulian. Interactions of Membrane-Active Peptides with Thick, Neutral, Non-Zwitterionic Bilayers. 2005. J. Phys. Chem B. 109:14356-14364.

Goulian, M. Robust Control in Bacterial Regulatory Circuits. 2004. Curr. Opin. Microbiol. 7:198-202.

Batchelor, E., T.J. Silhavy and M. Goulian. 2004. Continuous Control in Bacterial Regulatory Circuits. J. Bacteriol. 186:7618-7635.

Batchelor, E. and M. Goulian. 2003. Robustness and the Cycle of Phosphorylation and Dephosphorylation in a Two-Component Regulatory System. Proc. Nat. Acad. Sci. 100:691-696.

Goulian, M. and S.M. Simon, Tracking Single Proteins within Cells. 2000. Biophys. J. 79:2188-2198.