Project 5: Evolvability and robustness in simple synthetic modules (Elowitz) (#31-32) We studied the role of noise in natural and man-made bacterial transcriptional networks. Our original aim of exploring the evolvability of these modules led us to methods to analyze them more precisely, by asking how noise affects their operation: 1) We performed a study of the cis-regulatory logic in prokaryotic promoters, based on a combinatorial promoter library composed of modular sequence elements. This study identified a number of heuristic rules for programming and modulating the combinatorial logic behavior of prokaryotic promoters. 2) We analyzed transient differentiation system that leads to competence in B. subtilis. To understand the operation of this excitable switch, we varied promoter strengths, circuit architecture, and stochastic fluctuations (noise). We identified the independent tuning of differentiation frequency and duration as a design principle, and showed that noise (fluctuations) is actually required for cellular differentiation37.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM068763-09
Application #
8337770
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
9
Fiscal Year
2011
Total Cost
$239,791
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
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Lavrentovich, Maxim O; Wahl, Mary E; Nelson, David R et al. (2016) Spatially Constrained Growth Enhances Conversional Meltdown. Biophys J 110:2800-2808

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