There is increasing evidence in Escherichia coli that certain operons, though scattered on the genetic map and having separate controls, may also be subject to common, global controls that coordinate their expression. In many cases the co-regulated genes share a common regulator molecule and are called a regulon. Co-regulated proteins can be recognized by two dimensional gel electrophoresis that resolves total cellular protein; co-regulated genes can be discovered with the aid of new genetic techniques involving fusing the Beta-galactosidase gene to promoters at random throughout the genome. These and other genetic and biochemical techniques can then be used to identify the proteins, map their genes and analyze the nature of their control. This project is directed at discovering and analyzing the regulons that are involved in the response of E. coli to changes in temperature, phosphate supply, and the availability of molecular oxygen. A shift to high temperature activates a regulon of 13 genes controlled by a single regulatory gene through its protein product. A mutant deficient in this protein dies at temperatures permitting growth of normal cells. Analysis of this regulon and the molecular mechanism of its control is particularly significant because it constitutes E. coli's version of the biologically universal """"""""heat shock"""""""" response of cells to high temperature and certain other stress. Deprival of phosphate induces a complex response involving induction of at least 20 operons, and adaptation to grow anaerobically or in the presence of oxygen similarly involves multigene responses. In addition to defining and analyzing the regulons involved in these responses, we shall examine the recent discovery that global control systems overlap. We shall determine the extent of this overlap among the major global control systems of E. coli, learn its molecular basis, and evaluate its role in metabolic integration. Our long range objective is an understanding how the bacterial cell coordinates the thousand or so individual chemical reactions necessary for growth. Analysis of multigenic (global) control systems should help us understand E. coli, where the work is most readily done, and should provide valuable leads to metabolic integration and gene coordination in more complex cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM017892-18
Application #
3269152
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1978-09-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
18
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Peruski Jr, L F; Neidhardt, F C (1994) Identification of a conditionally essential heat shock protein in Escherichia coli. Biochim Biophys Acta 1207:165-72
Nystrom, T; Neidhardt, F C (1994) Expression and role of the universal stress protein, UspA, of Escherichia coli during growth arrest. Mol Microbiol 11:537-44
Welch, T J; Farewell, A; Neidhardt, F C et al. (1993) Stress response of Escherichia coli to elevated hydrostatic pressure. J Bacteriol 175:7170-7
Nystrom, T; Neidhardt, F C (1993) Isolation and properties of a mutant of Escherichia coli with an insertional inactivation of the uspA gene, which encodes a universal stress protein. J Bacteriol 175:3949-56
Gage, D J; Neidhardt, F C (1993) Adaptation of Escherichia coli to the uncoupler of oxidative phosphorylation 2,4-dinitrophenol. J Bacteriol 175:7105-8
Gage, D J; Neidhardt, F C (1993) Modulation of the heat shock response by one-carbon metabolism in Escherichia coli. J Bacteriol 175:1961-70
Jones, P G; Cashel, M; Glaser, G et al. (1992) Function of a relaxed-like state following temperature downshifts in Escherichia coli. J Bacteriol 174:3903-14
Nystrom, T; Neidhardt, F C (1992) Cloning, mapping and nucleotide sequencing of a gene encoding a universal stress protein in Escherichia coli. Mol Microbiol 6:3187-98
Lin, R; Ernsting, B; Hirshfield, I N et al. (1992) The lrp gene product regulates expression of lysU in Escherichia coli K-12. J Bacteriol 174:2779-84
VanBogelen, R A; Sankar, P; Clark, R L et al. (1992) The gene-protein database of Escherichia coli: edition 5. Electrophoresis 13:1014-54

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