About
Research Profile
Research in my laboratory is focused in two areas, each of which takes advantage of extensive collaborations with other University of Michigan investigators.
One project [Genetic Systems Bioengineering for Escherichia coli, GM063642, NIGMS] is to develop synthetic genetic circuitry that performs various computations, such as oscillators, toggle switches, and logic gates. One goal of these synthetic biology approaches is to provide a quantitative understanding of complex genetic regulatory processes through comparison of experimental data and mathematical models. Another goal is to develop the components and knowledge base to allow the engineering of synthetic biology devices with useful applications ranging from protein expression systems to computers that contain a living processor.
Another project is to study the design principles of signal transduction systems that employ reversible covalent modification. [Funded in part by Characterization of the Escherichia coli NRI/NRII Signal Transduction System, GM059637, NIGMS]. Current efforts are focused on understanding the two bicyclic signal transduction systems controlling glutamine synthetase and nitrogen-regulated gene expression. These bicyclic signaling systems have been studied for over 20 years in our lab, and we have reconstituted the entire system from purified components as well as assembled a substantial collection of mutant proteins with alterations in almost all of the known activities. We are using these reconstituted systems as model experimental systems to study signal transduction system design principles that are generally applicable to all covalent modification cycles. One current approach investigates sources of ultrasensitivity in the systems (zero order, inhibitor, multi-site). Another current approach examines how sequestration of an enzyme by competing receptors alters the sensory capabilities of a covalent modification cycle. Another approach investigates retroactivity, or the “backwards” flow of information in signaling systems.
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