Special mechanisms of mutation are induced in bacteria, yeast and human cells under growth-limiting stress, under the control of stress responses. These mechanisms increase genetic diversity and potentially the ability to evolve specifically when cells are maladapted to their environment, i.e., when they are stressed. Stress-synchronous- mutation mechanisms may provide superior models for genetic changes that drive pathogen-host adaptation, antibiotic resistance, aging, cancer progression and therapy- resistance mechanisms, and possibly much of evolution generally. This project is an investigation of three molecular mechanisms of stress-synchronous genomic instability in E. coli, with a goal of finding common themes. Because the mechanisms studied have common components with several other (less understood) mechanisms of stress- synchronous mutation, the results should provide both important models for understanding the problems listed above and specific tools for combating antibiotic resistance.

Public Health Relevance

This project will provide new ways to approach and combat problems of development of cancers, evolution of cancer-chemotherapy resistance, aging, microbial pathogenesis and antibiotic resistance among other serious problems in human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM053158-18
Application #
8710238
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Janes, Daniel E
Project Start
1995-09-30
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
18
Fiscal Year
2014
Total Cost
$678,786
Indirect Cost
$245,057
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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Galhardo, Rodrigo S; Do, Robert; Yamada, Masami et al. (2009) DinB upregulation is the sole role of the SOS response in stress-induced mutagenesis in Escherichia coli. Genetics 182:55-68

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