PROJECT 5

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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.