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Identification and characterization of factors affecting cytoskeletal proteins--the mediators of bacterial cell shape

Award Number: SC3GM121234
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY In general, mediators of bacterial cell shape via the cytoskeleton are not well understood. We will explore the interplay of the cytoskeleton and cell shape based on three promising observations. First, we have identified a phospholipid synthase (CC1159) that, when overexpressed, causes the bacterium Caulobacter crescentus to change its shape from a crescent to a rod-shaped morphology by inhibiting the localization and function of the intermediate filament protein known as crescentin. Second, overexpression of a catalytically inactive version of the phospholipid synthase still mediates the change in cell shape, suggesting that the phenotype results from a protein-protein interaction instead of elevated levels of a phospholipid. Third, bacterial two-hybrid data suggest that our phospholipid synthase interacts with itself and with cytosine triphosphate synthase (CtpS), which also induces a rod-shaped morphology when overexpressed via interaction with crescentin. Human homologs of crescentin, the intermediate filament nuclear Lamins A/C, are implicated in premature aging and muscular dystrophy, and we suggest a link between phospholipid synthesis and intermediate filaments in C. crescentus that may parallel their human homologs. Research in the eukaryotic literature is just starting to link phospholipids/sphingolipids [and glycosylphosphatidylinositol-anchored proteins (GPI-AP)] with intermediate filaments, suggesting that our investigations in C. crescentus may be relevant to humans. Additionally, Helicobacter pylori's and Vibrio cholerae's crescent shape contributes to host colonization and pathogenesis. Thus, our findings may be also relevant to cell shape and pathogenicity of these human pathogens.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	THE UNIVERSITY CORPORATION	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	12/5/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $108,750 )
2021	2021	UNIVERSITY CORPORATION, THE	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	4/12/2021	NON-COMPETING CONTINUATION	$108,750
														Subtotal = $108,750

Issue Date FY: 2020 ( Subtotal = $108,750 )
2020	2020	UNIVERSITY CORPORATION, THE	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	4/7/2020	NON-COMPETING CONTINUATION	$108,750
														Subtotal = $108,750

Issue Date FY: 2019 ( Subtotal = $108,750 )
2019	2019	UNIVERSITY CORPORATION, THE	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	4/2/2019	NON-COMPETING CONTINUATION	$108,750
														Subtotal = $108,750

Issue Date FY: 2018 ( Subtotal = $108,750 )
2018	2018	UNIVERSITY CORPORATION, THE	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	4/23/2018	NEW	$108,750
														Subtotal = $108,750

Grand Total All Awards = $435,000

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Identification and characterization of factors affecting cytoskeletal proteins--the mediators of bacterial cell shape

Award Number: SC3GM121234

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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