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, bsgA, which are defective in one of the required cell-cell interactions occuring early in development. The primary defect is loss of an essential protease. As a result of the protease defect, these strains a) produce an extracellular, diffusible molecule which acts as an inhibitor of developmental gene expression by the mutant cells or by neighboring wild-type cells, and b) fail to transcribe any of the known developmentally induced genes. The first objective of this study is to understand the nature of this inhibitory signal; specifically: 1) to identify this inhibitory molecule, 2) to identify the genes required for its synthesis, degradation and interaction with cells, 3) to understand the role of this inhibitor in the development of wild-type cells. The second objective of this study is to understand the mechanism by which the defect in proteolysis affects a) production and/or degradation of the inhibitory factor, and b) developmental gene transcription. The long range goal of this project 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 bay 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 #
2R01GM031900-09A1
Application #
3280315
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1983-04-01
Project End
1996-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
9
Fiscal Year
1992
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

Showing the most recent 10 out of 12 publications