Monday, September 1, 2025 9/1/2025

Spatiotemporal regulation of bacterial cell envelope assembly

Award Number: R35GM146993
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

Spatiotemporal regulation of bacterial cell envelope assembly - Project Summary/Abstract Despite their small size, bacterial cells precisely synchronize cellular processes in space and time. The cell envelopes of bacteria are complex and dynamic structures that are coordinately assembled during the cell cycle. Cell wall anchored surface proteins of Gram-positive bacteria are major cell envelope components, which are secreted across the cytoplasmic membrane and covalently attached to cell wall peptidoglycan by sortase A (SrtA). Strikingly, many surface proteins contain a specific YSIRK/G-S signal peptide that targets proteins to the cross-wall during cell division. Coordinated with cell division and cell wall synthesis, cross-wall targeting promotes efficient incorporation of surface proteins to the newly synthesized cross-wall peptidoglycan; however, the mechanisms remain unknown. It has been proposed that the YSIRK/G-S signal peptide promotes localized secretion at the division septum. However, by developing a new microscopy method in our model organism of Staphylococcus aureus, we now provide evidence that in contrast to the prevailing model, the targeting does not occur during secretion, but rather is SrtA-dependent. We further discovered that cross-wall targeting is regulated by another important cell envelope component: LtaS-mediated lipoteichoic acid (LTA) synthesis and D- alanylation of teichoic acids. Intriguingly, LTA synthesis and D-alanylation regulate different biogenesis stages: LTA regulates SrtA-mediated septal anchoring whereas D-alanylation modulates cross-wall deposition. Collectively, these recent discoveries from my own lab form the foundation of my independent research program for this MIRA application. We will elucidate the distinct mechanisms by which the YSIRK/G-S signal peptide, LTA synthesis and D-alanylation spatially regulate surface protein biogenesis during the cell cycle. Successful completion of the research projects will not only reveal novel mechanisms underlying surface protein biogenesis in Gram-positive bacteria, but also uncover novel functions of LTA and D-alanylation in cell envelope assembly, providing fundamental insight into how bacterial cells precisely coordinate cell envelope assembly during growth and cell division.


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: 2025 ( Subtotal = $363,863 )
2025	2025	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	4	8/19/2025	NON-COMPETING CONTINUATION	$363,863
														Subtotal = $363,863

Issue Date FY: 2024 ( Subtotal = $364,377 )
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	3	8/23/2024	NON-COMPETING CONTINUATION	$364,377
														Subtotal = $364,377

Issue Date FY: 2023 ( Subtotal = $364,823 )
2023	2023	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	2	8/14/2023	NON-COMPETING CONTINUATION	$364,823
														Subtotal = $364,823

Issue Date FY: 2022 ( Subtotal = $349,376 )
2022	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Biomedical Research and Research Training	000	1	9/20/2022	NEW	$349,376
														Subtotal = $349,376

Grand Total All Awards = $1,442,439

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Spatiotemporal regulation of bacterial cell envelope assembly

Award Number: R35GM146993

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/20/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer