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.