Ph.D., Harvard University, 1990
bacterial regulatory circuits, two-component signaling in E. coli, directed evolution of signaling circuits
Research in the Goulian lab is focused on the regulatory circuits that bacteria use to sense and respond to the environment. At present, most of the efforts in the lab explore aspects of two-component signaling in E. coli. Two-component systems make up a large family of regulatory circuits that mediate responses to diverse environmental signals and play a central role in bacterial physiology. In their simplest form, these circuits are composed of two proteins, a sensor kinase and a 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 and biochemical circuits. They 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 analyzed and compared. (The laboratory strain E. coli K-12 contains roughly 30 two-component systems). Current research applies techniques from genetics, bacterial physiology, fluorescence microscopy, and mathematical modeling to explore the principles underlying two-component systems and to identify the mechanisms that maintain fidelity in processing signals. New techniques to measure signaling activity, both across populations and at the level of single cells, are being developed in order to formulate and test quantitative models. In addition, synthetic networks are being engineered by rational design and directed evolution in order to build novel circuits and to explore the general constraints on cell signaling.
Click on PubMed link for Dr. Goulian's publications.