Joined the Department in 1992
- B.A., 1976, Northwestern University, Biochemistry.
- Ph.D., 1989, University of Wisconsin, Madison, Molecular Biology.
- Postdoctoral research: Harvard Medical School.
American Society of Microbiology
Genetics Society of America
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.
- Hudson, MA, Siegele, DA, Lockless, SW. Use of a Fluorescence-Based Assay To Measure Escherichia coli Membrane Potential Changes in High Throughput. Antimicrob Agents Chemother. 2020;64 (9):. doi: 10.1128/AAC.00910-20. PubMed PMID:32631824 PubMed Central PMC7449193.
- Siegele, DA, LaBonte, SA, Wu, PI, Chibucos, MC, Nandendla, S, Giglio, MG et al.. Phenotype annotation with the ontology of microbial phenotypes (OMP). J Biomed Semantics. 2019;10 (1):13. doi: 10.1186/s13326-019-0205-5. PubMed PMID:31307550 PubMed Central PMC6631659.
- Xia, J, Chiu, LY, Nehring, RB, Bravo Núñez, MA, Mei, Q, Perez, M et al.. Bacteria-to-Human Protein Networks Reveal Origins of Endogenous DNA Damage. Cell. 2019;176 (1-2):127-143.e24. doi: 10.1016/j.cell.2018.12.008. PubMed PMID:30633903 PubMed Central PMC6344048.
- Giglio, M, Tauber, R, Nadendla, S, Munro, J, Olley, D, Ball, S et al.. ECO, the Evidence & Conclusion Ontology: community standard for evidence information. Nucleic Acids Res. 2019;47 (D1):D1186-D1194. doi: 10.1093/nar/gky1036. PubMed PMID:30407590 PubMed Central PMC6323956.
- Chibucos, MC, Siegele, DA, Hu, JC, Giglio, M. The Evidence and Conclusion Ontology (ECO): Supporting GO Annotations. Methods Mol Biol. 2017;1446 :245-259. doi: 10.1007/978-1-4939-3743-1_18. PubMed PMID:27812948 PubMed Central PMC6377151.
- Chibucos, MC, Zweifel, AE, Herrera, JC, Meza, W, Eslamfam, S, Uetz, P et al.. An ontology for microbial phenotypes. BMC Microbiol. 2014;14 :294. doi: 10.1186/s12866-014-0294-3. PubMed PMID:25433798 PubMed Central PMC4287307.
- Lim, B, Miyazaki, R, Neher, S, Siegele, DA, Ito, K, Walter, P et al.. Heat shock transcription factor σ32 co-opts the signal recognition particle to regulate protein homeostasis in E. coli. PLoS Biol. 2013;11 (12):e1001735. doi: 10.1371/journal.pbio.1001735. PubMed PMID:24358019 PubMed Central PMC3866087.
- Hu, JC, Sherlock, G, Siegele, DA, Aleksander, SA, Ball, CA, Demeter, J et al.. PortEco: a resource for exploring bacterial biology through high-throughput data and analysis tools. Nucleic Acids Res. 2014;42 (Database issue):D677-84. doi: 10.1093/nar/gkt1203. PubMed PMID:24285306 PubMed Central PMC3965092.
- Gene Ontology Consortium, Blake, JA, Dolan, M, Drabkin, H, Hill, DP, Li, N et al.. Gene Ontology annotations and resources. Nucleic Acids Res. 2013;41 (Database issue):D530-5. doi: 10.1093/nar/gks1050. PubMed PMID:23161678 PubMed Central PMC3531070.
- Renfro, DP, McIntosh, BK, Venkatraman, A, Siegele, DA, Hu, JC. GONUTS: the Gene Ontology Normal Usage Tracking System. Nucleic Acids Res. 2012;40 (Database issue):D1262-9. doi: 10.1093/nar/gkr907. PubMed PMID:22110029 PubMed Central PMC3245169.