Friday, June 20, 2025 6/20/2025

Serine hydrolase regulators of Mycobacterium tuberculosis non-replicating states

Award Number: R21AI137571
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/09/2018
PERIOD OF PERFORMANCE END DATE: 09/30/2018

Group Awards By:

View Award Description

Serine hydrolase regulators of Mycobacterium tuberculosis non-replicating states - Abstract The transition from replication to non-replication underlies much of Mycobacterium tuberculosis (Mtb) pathogenesis, as non- or slowly replicating Mtb are responsible for persistence and latency and for the long treatment times required to clear Mtb infection. Defining the molecular programs that drive the transition to a state of slow or no replication is central for understanding Mtb pathogenesis and for discovering new drugs that can shorten treatment times. However, there are currently no effective tools to directly identify druggable enzyme activity in the non-replicating state. While previous studies have measured genome-wide transcript or protein abundance in non-replicating cells, these measurements are only approximations of biological activity. A powerful approach to directly measure global enzymatic activity is activity-based protein profiling (ABPP). ABPP directly measures biochemical activity of entire families of enzymes by recognizing a shared catalytic mechanism. This approach is particularly suited for the detection of serine hydrolase (SH) activity, a large enzyme family central to all aspects of metabolism that is extensively regulated by posttranslational modifications. The central role of SHs in many metabolic pathways makes SHs unique reporters for a broad cross-section of Mtb metabolism, and combined with their proven druggability, also tractable drug targets. We developed a chemical proteomics approach to directly measure global SH activity and to define the activity changes between replicating and non-replicating Mtb. We show that SHs are extensively regulated depending on Mtb's replication state. We defined three groups of coordinately regulated SHs in the Mtb life cycle, each indicating a different role in inducing or maintaining the non-replicating state. Here, we will test the hypothesis that a small group of coordinately regulated SHs active ONLY during non-replication are regulators of and potential drug targets in non-replicating Mtb.


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: 2022 ( Subtotal = -$7,377 )
2022	2019	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	000	3	11/17/2021	NON-COMPETING CONTINUATION	-$7,378
2022	2018	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	001	1	9/26/2022	NEW	$1
														Subtotal = -$7,377

Issue Date FY: 2019 ( Subtotal = $225,888 )
2019	2019	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	002	3	4/23/2019	NON-COMPETING CONTINUATION	$235,375
2019	2018	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	12/19/2018	NEW	-$241,486
2019	2018	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	003	1	4/30/2019	NEW	$0
2019	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	001	2	12/19/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$231,999
														Subtotal = $225,888

Issue Date FY: 2018 ( Subtotal = $294,000 )
2018	2018	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	5/8/2018	NEW	$294,000
														Subtotal = $294,000

Grand Total All Awards = $512,511

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Serine hydrolase regulators of Mycobacterium tuberculosis non-replicating states

Award Number: R21AI137571

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/09/2018

PERIOD OF PERFORMANCE END DATE: 09/30/2018

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer