Synthetic Genetic Devices as Model Systems for Quantitative Studies of Genetic Regulation (A. Ninfa, Professor of Biological Chemistry, and D. Forger)

Synthetic genetic systems are useful because these devices can be used for various applications, and because they provide the ideal tool for the study of signal transduction system design principles. Our first synthetic genetic system is a genetic clock that results in "circadian" periodicity of gene expression in E. coli. Our current version of the clock results in periodic expression of the lacZYA operon in large populations of cells grown in a chemostat. By a combination of theoretical studies and experimental studies in our lab, we hope to improve clock function and elucidate the system design principles responsible for its function.

Project overview: Our research group is focused upon designing, fabricating, and characterizing synthetic genetic systems that bring about interesting behaviors, such as oscillators (clocks), toggle switches, and systems for spatial and temporal organization of gene expression. Our basic approachs include an iterative process of model development, fabrication of the synthetic genetic circuitry described by the models, and measurement of system behaviors in intact cells. Increasingly sophisticated ODE and PDE models are used to capture dynamical properties of the systems and predict improved system designs. Ongoing projects include synthetic genetic devices that have been through extensive modeling and experimental characterization as part of an NIH-supported project. These ongoing projects provide an infrastructure of modeling and experimental approaches that will be utilized to support new project development.

We are currently looking to recruit a team of undergraduate students to develop a synthetic genetic system that captures essential features of tissue development, including irreversible differention into one of two alternative cell types in response to transient signals, and where differentiated cells determine the fates of their neighbors and form defined boundarys with other cell types. Student members of the team will be exposed to all aspects of synthetic genetic system development, and may specialize in specific areas such as modeling or fabrication as per their interests. Students will be encouraged to interact with the University of Michigan Synthetic Biology team, consisting of diverse undergraduates competing in the Internations Genetically Engineered Machines (iGEM) competition.

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