Theory and experiment will be combined to study three unanswered questions regarding the bacterial chemotaxis signaling pathway: (i) the mechanism of signal amplification and integration in receptor clusters localized at cell poles, (ii) the mechanism of motor switching, which results from interactions between the response regulator protein CheY and the switch complex of the flagellar motor, and (iii) how these and other mechanisms contribute to, and are affected by signal fluctuations in the pathway. The project is designed to incorporate the answers to each of these questions, as they are resolved, into the most detailed computational model of the bacterial chemotaxis pathway to date. A specific focus will be on extending the fluorescence resonance energy transfer (FRET) system developed by Berg and colleagues for real-time measurements of the intracellular signaling state.
The aim i s to enable such measurements in single cells over extended periods, which would allow for direct comparisons with stochastic simulations of the pathway. It is expected that the methods developed will be applicable to many other cell signaling systems, and the results obtained should provide insight into the nature of other mesoscopic phenomena in the cell.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI063747-02
Application #
7020026
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Korpela, Jukka K
Project Start
2005-02-08
Project End
2008-02-07
Budget Start
2006-02-08
Budget End
2007-02-07
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Shimizu, Thomas S; Tu, Yuhai; Berg, Howard C (2010) A modular gradient-sensing network for chemotaxis in Escherichia coli revealed by responses to time-varying stimuli. Mol Syst Biol 6:382
Tu, Yuhai; Shimizu, Thomas S; Berg, Howard C (2008) Modeling the chemotactic response of Escherichia coli to time-varying stimuli. Proc Natl Acad Sci U S A 105:14855-60
Shimizu, Thomas S; Delalez, Nicolas; Pichler, Klemens et al. (2006) Monitoring bacterial chemotaxis by using bioluminescence resonance energy transfer: absence of feedback from the flagellar motors. Proc Natl Acad Sci U S A 103:2093-7