- B.A., Biochemistry and Molecular Biology, Northwestern University
- Ph.D., Molecular Biology, University of Wisconsin-Madison
- Postdoc., Harvard Medical School
Entering and Exiting Stationary Phase in E. coli
Understanding how cells sense and adapt to environmental changes is a fundamental biological problem. Bacteria provide an excellent system for studying how cells coordinate global gene expression and physiology to thrive under diverse conditions. Bacteria have evolved a variety of mechanisms that allow them to survive in environments where they must cope with periodic starvation. Most bacteria do not respond to starvation by "running out of gas" and arresting all metabolic activity. Instead they carry out starvation-induced programs that allow them to exit the growth cycle, maintain viability during starvation, and resume growth when nutrients again become available. My laboratory is working to understand the mechanisms that control how E. coli cells enter and exit stationary phase in response to changes in nutrient availability.
The transitions between exponential growth and stationary phase involve striking changes in the pattern of gene expression. Understanding how these different physiological programs are initiated involves determining how gene expression is regulated during each transition. A major research focus in the lab is identifying and characterizing the regulatory factors controlling the changes in gene expression that occur when cells are starved and when starved cells are provided with fresh nutrients.
Genes whose expression is induced as cells enter or exit stationary phase have been identified and are being used as reporters to isolate regulatory mutants that alter their expression. Once identified genetically, these regulatory factors will be characterized at the molecular level.
The general starvation response is induced when cells are starved for carbon, nitrogen, or phosphorus or enter stationary phase in rich medium. Each of these conditions dramatically induces transcription from Pmcb, the promoter for the microcin B17 operon. Regulation of Pmcb transcription is independent of other pathways known to control starvation-induced gene expression. Therefore, characterizing the factors controlling Pmcb should identify a new regulatory pathway in the general starvation response in E. coli.
We have identified a group of E. coli proteins expressed exclusively or primarily during outgrowth from stationary phase. The limited time when these proteins are synthesized suggests the existence of mechanisms controlling their expression, which may also be involved in controlling the outgrowth response. Identifying the genes encoding these proteins and the factors controlling their expression will be an important first step toward understanding this phase of the bacterial life cycle.