? The design of complex synthetic genetic circuits requires the availability of many communication modules that can be combined in circuits without significant crosstalk. Development of these modules requires identification of transcription factors that respond to specific chemical signals and transduce this signal at specific promoters. Bacterial quorum sensing systems are a rich source for potential communication modules.
The aim of this proposal is to use directed evolution to increase sensitivity of the LuxR family member RhIR to its cognate AHL, C4HSL, and to generate variants of RhIR that respond to various noncognate AHLs. RhIR-responsive promoters will also be engineered for higher sensitivity and altered growth phase response. Mutant RhIR transcription factors and engineered promoters will be characterized using mathematical modeling and experimental observation to generate communication modules with increased sensitivity. This work will increase our understanding of RhIR function in quorum sensing, and the new modules that are generated will be useful tools for the design of complex synthetic genetic circuits. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM078975-02
Application #
7254881
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Portnoy, Matthew
Project Start
2006-06-01
Project End
2009-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
2
Fiscal Year
2007
Total Cost
$45,976
Indirect Cost
Name
California Institute of Technology
Department
Chemistry
Type
Schools of Engineering
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Dougherty, Michael J; Arnold, Frances H (2009) Directed evolution: new parts and optimized function. Curr Opin Biotechnol 20:486-91