Areas of Interest
Research in my laboratory is focused in two areas, each of which takes advantage of extensive collaborations with other University of Michigan investigators.
The first project 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. 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.
Honors & Awards
Endowment for Basic Sciences Teaching Award, University of Michigan Medical School, 2015
Henry Russel Award, University of Michigan, 1999
Characterization of the reconstituted UTase/UR-PII-NRII-NRI bicyclic signal transduction system that controls the transcription of nitrogen-regulated (Ntr) genes in Escherichia coli.
Jiang P, Ventura AC, Ninfa AJ.
Biochemistry. 2012; 51: 9045-57.
The robustness of the Escherichia coli signal-transducing UTase/UR-PII covalent modification cycle to variation in the PII concentration requires very strong inhibition of the UTase activity of UTase/UR by glutamine.
Jiang P, Zhang Y, Atkinson MR, Ninfa AJ.
Biochemistry. 2012; 51: 9032-44.
Synthetic networks: oscillators and toggle switches for Escherichia coli.
Perry N, Ninfa AJ.
Methods Mol Biol. 2012; 813: 287-300.
A source of ultrasensitivity in the glutamine response of the bicyclic cascade system controlling glutamine synthetase adenylylation state and activity in Escherichia coli.
Jiang P, Ninfa AJ.
Biochemistry. 2011; 50: 10929-40.
Load-induced modulation of signal transduction networks.
Jiang P, Ventura AC, Sontag ED, Merajver SD, Ninfa AJ, Del Vecchio D.
Sci Signal. 2011; 4: ra67.
Unnecessary signaling: poorly named?
J Bacteriol. 2011; 193: 4571-3.
For a list of publications from PubMed, click HERE