The goal of this research is to elucidate the mechanisms that govern cellular differentiation using as a model system the transformation of a growing cell into a dorman spore in the bacterium Bacillus subtilis. Sporulation involves a process of asymmetric division in which the developing cell is divided into large small and large progeny cells that communicate with each other through pathways of intracellular signal transduction. Traditional approaches to investigating sporulation have emphasized mechanisms operating at the level of solitary cells. But recent research additionally reveals antagonistic and cooperative interactions between cells poised to sporulate. Indeed, a major theme of this research is that a cell culture is a mixture in which individual cells are directed toward different fates and express different sets of genes. This proposal addresses important gaps in our knowledge by asking two well-defined questions whose answers are, thus far, only partially known: (I) how do regulatory circuits and morphogenetic events result in the conversion of a cell into a spore? (II) How does sporulation occur in the context of a multicellular community?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM018568-37
Application #
7560017
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Anderson, James J
Project Start
1976-02-01
Project End
2012-01-31
Budget Start
2009-02-01
Budget End
2010-01-31
Support Year
37
Fiscal Year
2009
Total Cost
$662,133
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
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Bradshaw, Niels; Levdikov, Vladimir M; Zimanyi, Christina M et al. (2017) A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases. Elife 6:
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DeFrancesco, Alicia S; Masloboeva, Nadezda; Syed, Adnan K et al. (2017) Genome-wide screen for genes involved in eDNA release during biofilm formation by Staphylococcus aureus. Proc Natl Acad Sci U S A 114:E5969-E5978
Flanagan, Kelly A; Comber, Joseph D; Mearls, Elizabeth et al. (2016) A Membrane-Embedded Amino Acid Couples the SpoIIQ Channel Protein to Anti-Sigma Factor Transcriptional Repression during Bacillus subtilis Sporulation. J Bacteriol 198:1451-63
Cabeen, Matthew T; Leiman, Sara A; Losick, Richard (2016) Colony-morphology screening uncovers a role for the Pseudomonas aeruginosa nitrogen-related phosphotransferase system in biofilm formation. Mol Microbiol 99:557-70

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