Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The critical roles of (p)ppGpp in homeostasis and antibiotic tolerance in Gram positive bacteria

Award Number: R35GM127088
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: 05/01/2018
PERIOD OF PERFORMANCE END DATE: 02/29/2028

Group Awards By:

View Award Description

The critical roles of (p)ppGpp in homeostasis and antibiotic tolerance in Gram positive bacteria - Project Summary Bacteria frequently encounter stresses including nutrient starvation, temperature changes, and antibiotic assault, which could easily throw their intracellular environment into chaos. To survive and to adapt, bacteria developed diverse stress responses to regulate intracellular processes accordingly. While the transcriptional networks governing stress responses have been extensively characterized, there are major gaps in our knowledge beyond transcription regulation. The theme of my research is to elucidate stress signaling mechanisms that are transmitted by rapid changes in concentration of ‘alarmones’ – signaling nucleotides which are instrumental for alerting cells about stresses in a timely manner. My laboratory has extensive experience in characterizing the conserved alarmone (p)ppGpp. (p)ppGpp is induced by stresses and mediates profound, pleiotropic physiological changes in almost all bacteria to allow fitness, survival, and evolution. We identified multiple purine synthesis enzymes, a replication enzyme and a transcription repressor that are directly regulated by (p)ppGpp in Gram-positive Bacillus species. These regulations were further found to be conserved in many pathogens and are critical for homeostasis, starvation resistance, antibiotic persistence, and genome integrity. Currently, we are also investigating how (p)ppGpp regulates the switch between distinct bacterial lifestyles: planktonic growth and biofilm formation. Additionally, we detected other nucleotide alarmones including AppppA, pGpp, ppApp, and c-di- AMP, which are induced by different stresses including temperature and cell wall stress, to form a robust protective network. Our future research will answer the following fundamental questions: How are the different alarmones triggered by different stresses, and how do bacteria synthesize them? What are the direct interaction targets of different alarmones, and how do they promote bacterial fitness and influence bacterial development such as biofilm formation and sporulation? How do bacteria integrate multiple cues from different alarmones for rapid and appropriate adaptation to diverse environments? We combine metabolomics, transcriptomics, and proteomics with biochemical and cell biological approaches to answer these questions. We obtained a list of alarmone targets from systematic screens performed with the proteome of the pathogen Bacillus anthracis. We will study these processes in the related non-pathogenic bacterium Bacillus subtilis for which we have extensive experience. B. subtilis grows fast and is highly amenable to genetic manipulation. The nucleotide signaling mechanisms we characterize in Bacillus are applicable to other, less tractable, pathogenic bacteria, and can be used for developing antimicrobial strategies by targeting their stress responses.


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: 2026 ( Subtotal = $456,560 )
2026	2026	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	9	2/26/2026	NON-COMPETING CONTINUATION	$456,560
														Subtotal = $456,560

Issue Date FY: 2025 ( Subtotal = $456,560 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	8	4/8/2025	NON-COMPETING CONTINUATION	$456,560
2025	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	7	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $456,560

Issue Date FY: 2024 ( Subtotal = $456,560 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	7	2/14/2024	NON-COMPETING CONTINUATION	$410,904
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	003	7	6/26/2024	NON-COMPETING CONTINUATION	$45,656
2024	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	002	6	2/14/2024	COMPETING CONTINUATION	$4,326
2024	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	5	2/14/2024	NON-COMPETING CONTINUATION	-$4,326
														Subtotal = $456,560

Issue Date FY: 2023 ( Subtotal = $456,560 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	6	4/27/2023	COMPETING CONTINUATION	$456,560
														Subtotal = $456,560

Issue Date FY: 2022 ( Subtotal = $373,143 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	5	4/26/2022	NON-COMPETING CONTINUATION	$373,143
														Subtotal = $373,143

Issue Date FY: 2021 ( Subtotal = $400,260 )
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	4	9/1/2021	SUPPLEMENT FOR EXPANSION	$27,117
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	4	4/14/2021	NON-COMPETING CONTINUATION	$373,143
														Subtotal = $400,260

Issue Date FY: 2020 ( Subtotal = $373,143 )
2020	2020	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	3	5/4/2020	NON-COMPETING CONTINUATION	$373,143
														Subtotal = $373,143

Issue Date FY: 2019 ( Subtotal = $373,143 )
2019	2019	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	2	5/1/2019	NON-COMPETING CONTINUATION	$373,143
														Subtotal = $373,143

Issue Date FY: 2018 ( Subtotal = $599,196 )
2018	2018	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	001	1	9/13/2018	SUPPLEMENT FOR EXPANSION	$226,053
2018	2018	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Biomedical Research and Research Training	000	1	3/6/2018	NEW	$373,143
														Subtotal = $599,196

Grand Total All Awards = $3,945,125

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The critical roles of (p)ppGpp in homeostasis and antibiotic tolerance in Gram positive bacteria

Award Number: R35GM127088

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: 05/01/2018

PERIOD OF PERFORMANCE END DATE: 02/29/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer