The idea of modular organization is especially appealing in bacteria, organisms that place genes of related function in operons, single transcriptional units. We will investigate the control of the transcriptional modules that make up the cell division cycle. Stable progression through the cell cycle requires exquisite information processing abilities. Cells must receive and integrate a variety of intracellular and environmental signals. These signals must be translated and coupled to execution of cell cycle events to ensure genetic stability and the production of viable daughter cells. Our work focuses on Caulobacter crescentus, a tractable model system for studying information processing during the prokaryotic cell cycle. Initial global studies of the genetic network governing this organism's cell cycle revealed an elaborate, modular structure (Laub et al., 2000). As Caulobacter cells progress through the cell cycle, batteries of genes are precisely turned on and off in accord with their demand in executing cell cycle events. Regulation of these temporal changes in expression is accomplished in large part by the action of two-component signal transduction genes. There are more than 100 of these regulatory genes in the Caulobacter genome and our global studies revealed that nearly a third are themselves differentially expressed during the cell cycle. However, the precise roles and responsibilities of these regulators is still unclear. Our goal is to produce a detailed, molecular-level map of the genetic modules controlling cell cycle progression in Caulobacter. To continue our efforts to produce such a map, we will use a combination of functional genomics, proteomics, and genetic manipulations to, i) identify modules using transcriptional profiling and quantitative, parallel fitness analysis, ii) characterize the connectivity of the regulatory network of two component protein kinases that control many of the modules in bacterial cells, and iii) dissect the design principles of regulatory modules by sensitively measuring the effects of removing one or more of several redundant levels of regulation.
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