Myxococcus xanthus is a gram negative bacterium which undergoes a simple cycle of multicellular development. It is an experimentally attractive organism in which to study the role of cell-cell interactions in the regulation of gene expression. The obligatory involvement of intercellular communication during its developmental program is implicated by the behavior of several developmentally defective mutants. The research described in this proposal will focus on one group of mutants which apparently fail to produce an intercellular signal required for the expression of several developmentally induced genes. The objective of this study is to understand the nature of this signal and the mechanism by which it modifies gene expression. Classical genetics will be augmented by gene fusion and recombinant DNA technology to determine which genes are required for the cell's response to the signal and to identify the specific regulatory steps by which the signal controls gene expression. Mutations affecting regulatory sites within promoters regulated by the signal will be generated by oligonucleotide directed mutagenesis, and analyzed by DNA sequence analysis. The signal molecule itself will be purified and the biochemical consequences of its interaction with cells will be characterized. The long range goal of this research is to understand the means by which this organism coordinates the behavior of individual cells during multicellular activities. The problem of multicellular coordination is a fundamental problem in developmental biology. The information provided by this work may help to provide a framework for thinking about tissue interactions in more complex organisms. In this way it is hoped that this work may help us to understand situations in which intercellular coordination goes awry; situations which may in part lead to tragedies such as birth defects and malignancies.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031900-06
Application #
3280318
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1983-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Cusick, John K; Gill, Ronald E (2005) The bcsA gene influences multiple aspects of development in Myxococcus xanthus. Curr Microbiol 51:336-43
Cusick, John K; Hager, Elizabeth; Gill, Ronald E (2002) Characterization of bcsA mutations that bypass two distinct signaling requirements for Myxococcus xanthus development. J Bacteriol 184:5141-50
Tse, Hubert; Gill, Ronald E (2002) Bypass of A- and B-signaling requirements for Myxococcus xanthus development by mutations in spdR. J Bacteriol 184:1455-7
Hager, E; Tse, H; Gill, R E (2001) Identification and characterization of spdR mutations that bypass the BsgA protease-dependent regulation of developmental gene expression in Myxococcus xanthus. Mol Microbiol 39:765-80
Johansen, K A; Gill, R E; Vasil, M L (1996) Biochemical and molecular analysis of phospholipase C and phospholipase D activity in mycobacteria. Infect Immun 64:3259-66
Fisseha, M; Gloudemans, M; Gill, R E et al. (1996) Characterization of the regulatory region of a cell interaction-dependent gene in Myxococcus xanthus. J Bacteriol 178:2539-50
Laue, B E; Gill, R E (1995) Using a phase-locked mutant of Myxococcus xanthus to study the role of phase variation in development. J Bacteriol 177:4089-96
Laue, B E; Gill, R E (1994) Use of a phase variation-specific promoter of Myxococcus xanthus in a strategy for isolating a phase-locked mutant. J Bacteriol 176:5341-9
Gill, R E; Karlok, M; Benton, D (1993) Myxococcus xanthus encodes an ATP-dependent protease which is required for developmental gene transcription and intercellular signaling. J Bacteriol 175:4538-44
Gill, R E; Cull, M G; Fly, S (1988) Genetic identification and cloning of a gene required for developmental cell interactions in Myxococcus xanthus. J Bacteriol 170:5279-88

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