Differentiation of the bacterium Bacillus subtilis from the vegetative form into a dormant endospore has provided a powerful model for the study of fundamental problems in developmental biology. The overall goal is to understand how gene expression is coordinated with the assembly of cellular structures during differentiation. At the onset of sporulation a phosphorelay system controls the timing of early gene expression. As differentiation continues gene expression is coupled to the completion of specific morphological landmarks, and is synchronized between two cells. Additionally, morphogenetic proteins guide, and possibly regulate, the construction of sub-cellular structures. In this proposal we will investigate regulatory mechanisms that operate at each of these stages of development. In the first aim we will examine how two response regulators (Spo0A and PhoP) interact to produce two phenotypically different fractions of a clonal population. In the second aim we examine the role of newly discovered channel that connects two cells (forespore and mother cell) during endospore development, and in the third aim investigate the potential roles of two transcription factors in cell-type specific restriction of RNA polymerase sigma factor activity. In the final aim we examine the role of a GTP/ATP hydrolyzing protein in the assembly of the complex coat protein structure of endospores. Success in any one of these aims would represent substantial new information, and significantly impact our ideas in broad areas of cell biology and intercellular communication.

Public Health Relevance

The bacterium Bacillus subtilis, is related to bacteria that are important human pathogens. However, B. subtilis is more amenable to analysis. Therefore, the results of this research will more readily provide insights into the molecular mechanisms governing the growth, survival, and other biological activities of these related pathogenic bacteria.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054395-29
Application #
8197418
Study Section
Special Emphasis Panel (ZRG1-IDM-A (02))
Program Officer
Maas, Stefan
Project Start
1996-06-01
Project End
2012-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
29
Fiscal Year
2012
Total Cost
$349,406
Indirect Cost
$123,983
Name
Emory University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Meisner, Jeffrey; Maehigashi, Tatsuya; Andre, Ingemar et al. (2012) Structure of the basal components of a bacterial transporter. Proc Natl Acad Sci U S A 109:5446-51
Meisner, Jeffrey; Moran Jr, Charles P (2011) A LytM domain dictates the localization of proteins to the mother cell-forespore interface during bacterial endospore formation. J Bacteriol 193:591-8
Serrano, Monica; Real, Goncalo; Santos, Joana et al. (2011) A negative feedback loop that limits the ectopic activation of a cell type-specific sporulation sigma factor of Bacillus subtilis. PLoS Genet 7:e1002220
Kumar, Amrita; Moran Jr, Charles P (2008) Promoter activation by repositioning of RNA polymerase. J Bacteriol 190:3110-7
Meisner, Jeffrey; Wang, Xin; Serrano, Monica et al. (2008) A channel connecting the mother cell and forespore during bacterial endospore formation. Proc Natl Acad Sci U S A 105:15100-5
Serrano, Monica; Vieira, Filipe; Moran Jr, Charles P et al. (2008) Processing of a membrane protein required for cell-to-cell signaling during endospore formation in Bacillus subtilis. J Bacteriol 190:7786-96
Henriques, Adriano O; Moran Jr, Charles P (2007) Structure, assembly, and function of the spore surface layers. Annu Rev Microbiol 61:555-88
Guillot, Chris; Moran Jr, Charles P (2007) Essential internal promoter in the spoIIIA locus of Bacillus subtilis. J Bacteriol 189:7181-9
Costa, Teresa; Serrano, Monica; Steil, Leif et al. (2007) The timing of cotE expression affects Bacillus subtilis spore coat morphology but not lysozyme resistance. J Bacteriol 189:2401-10
Chen, Guangnan; Kumar, Amrita; Wyman, Travis H et al. (2006) Spo0A-dependent activation of an extended -10 region promoter in Bacillus subtilis. J Bacteriol 188:1411-8

Showing the most recent 10 out of 33 publications