Abstract

: Using well-characterized transcription factors from E. coli, we have constructed a synthetic genetic clock that produces a synchronous oscillating output in large populations of bacteria. In the proposed work, physiological and genetic approaches will be used to study the function of the synthetic clock, identify the important design features of the clock, and better insulate the synthetic genetic system from interference by other cellular signal transduction systems. Biochemical studies are proposed to measure the key parameters involved in clock function, and theoretical studies will develop models of clock function. Modeling will be used to determine the relationship of parameters affecting clock function, and to design better clocks. The predictions of theoretical studies will be tested experimentally. By comparing the results of theoretical studies and experimentation, we will elucidate the system design principals underlying the function of the synthetic genetic clock. These studies will explore the usefulness of using synthetic genetic systems to study system design principles, develop the technology for the construction of synthetic genetic systems, and advance our understanding of the temporal regulation of gene expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063642-04
Application #
6777016
Study Section
Special Emphasis Panel (ZRG1-TMP (02))
Program Officer
Tompkins, Laurie
Project Start
2001-08-01
Project End
2006-03-31
Budget Start
2004-08-01
Budget End
2006-03-31
Support Year
4
Fiscal Year
2004
Total Cost
$294,450
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Perry, Nicolas; Ninfa, Alexander J (2012) Synthetic networks: oscillators and toggle switches for Escherichia coli. Methods Mol Biol 813:287-300
Forger, Daniel B (2011) Signal processing in cellular clocks. Proc Natl Acad Sci U S A 108:4281-5
Ninfa, Alexander J (2010) Use of two-component signal transduction systems in the construction of synthetic genetic networks. Curr Opin Microbiol 13:240-5
Chang, Dong-Eun; Leung, Shelly; Atkinson, Mariette R et al. (2010) Building biological memory by linking positive feedback loops. Proc Natl Acad Sci U S A 107:175-80
Conrad, Emery; Mayo, Avraham E; Ninfa, Alexander J et al. (2008) Rate constants rather than biochemical mechanism determine behaviour of genetic clocks. J R Soc Interface 5 Suppl 1:S9-15
Del Vecchio, Domitilla; Ninfa, Alexander J; Sontag, Eduardo D (2008) Modular cell biology: retroactivity and insulation. Mol Syst Biol 4:161
Atkinson, Mariette R; Savageau, Michael A; Myers, Jesse T et al. (2003) Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli. Cell 113:597-607
Atkinson, Mariette R; Pattaramanon, Narinporn; Ninfa, Alexander J (2002) Governor of the glnAp2 promoter of Escherichia coli. Mol Microbiol 46:1247-57