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Probing NADase function of bacterial Toll/interleukin-1 receptor (TIR) proteins: Starting with a CURE (Course-based Undergraduate Research Experience)

Award Number: R16AI182345
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: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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Probing NADase function of bacterial Toll/interleukin-1 receptor (TIR) proteins: Starting with a CURE (Course-based Undergraduate Research Experience) - Project Summary The growing threat of antimicrobial resistance underlies the need for novel therapeutics that target specific bacterial virulence mechanisms. Bacterial Toll/interleukin-1 receptor (TIR) domain-containing proteins were originally characterized based on their roles in immune evasion. Early reports demonstrated the ability of bacterial TIRs to interact with TIR signaling domains in Toll-like receptor (TLR) signaling pathways and block downstream innate immune responses. Subsequently, bacterial TIRs were found to hydrolyze nicotinamide adenine dinucleotide (NAD+), a central player in cellular metabolism. The significance of the NADase activity of bacterial TIRs for bacterial function and survival is not clear, and it also is not known whether NADase activity plays a role in bacterial TIR interference with host innate immune responses. We hypothesize that bacterial TIR NADase activity alters metabolic and signaling responses within both bacteria and host cells to contribute to bacterial virulence and interference with host immune responses. To test this, we will 1) determine the effects of TcpC NADase activity on bacterial survival within model hosts, 2) identify novel host molecular pathways targeted by TcpC, and 3) develop course-based undergraduate research experiences (CUREs) for analysis of model host responses to TcpC and its NADase activity. This project will provide research experiences for a diverse group of students and will generate research findings that will inform development of therapeutics that can regulate growth and survival of bacteria, including pathogenic species, or can mimic the functions of bacterial TIRs to modulate immune responses for the treatment of immune disorders.


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 = $149,620 )
2025	2025	TOWSON UNIVERSITY	8000 YORK RD	TOWSON	MD	21252	BALTIMORE	USA	Allergy and Infectious Diseases Research	000	1	7/31/2025	NEW	$149,620
														Subtotal = $149,620

Grand Total All Awards = $149,620

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Probing NADase function of bacterial Toll/interleukin-1 receptor (TIR) proteins: Starting with a CURE (Course-based Undergraduate Research Experience)

Award Number: R16AI182345

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: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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