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Regulation of Gene Expression

Carol A. Gross, UCSF

My overall interest is to study global regulatory networks in the bacterium E. coli, an organism that is amenable to genetic and biochemical approaches.

We study two different problems, each of which illuminates this issue from different perspectives. Our study of the heat shock response has led us into a consideration of how the cell monitors and regulates the folding state of proteins, how proteins are targeted for degradation and how the cytoplasmic and periplasmic compartments in E. coli are coordinated. Our study of transcriptional regulatory networks has led us to dissect the functional anatomy of RNA polymerase and to establish a genomics approach to discover the connections between different networks.

We have found that that E. coli mounts two distinct responses to heat and other stresses:

(1) a response measuring conditions in the cytoplasm, which is orchestrated by the alternative sigma factor σ32, and

(2) a response measuring conditions in the periplasm, which is orchestrated by the alternative sigma factor σE.

Each response senses protein folding as well as other, yet unknown signals. We are defining the molecular mechanisms of both regulatory cascades, as well as using the periplasmic response as a entry point to understand how events in the periplasm and cytoplasm are coordinated.

To understand how various cellular regulatory systems control RNA polymerase, we first delineate the functional anatomy of the enzyme and then investigate how altering its individual functions affects gene regulation. We are defining the conformational changes in sigma throughout initiation, defining the sigma-core interface and investigating its role in transcription process. As a complementary approach, we are using gene arrays to understand how perturbing RNA polymerase alters gene expression and to dissect the transcriptional regulatory network.

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