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Comparative Study on Human Beta Defensin Type 2 and 3 Interaction with Model Bacterial Lipid Membranes

Award Number: R15GM163254
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: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Comparative Study on Human Beta Defensin Type 2 and 3 Interaction with Model Bacterial Lipid Membranes - Abstract: Natural antimicrobial peptides (AMPs) are considered the solution to infectious diseases and the antibiotic inefficiency caused by bacterial resistance. Among natural AMPs, human beta defensin type 3 (hBD-3) is unique that it has a broader spectrum of and stronger antimicrobial activities against both Gram-positive and Gram-negative bacteria than other hBDs. It is believed that hBD-3 kills bacteria by directly disrupting bacterial lipid membranes, although its functional mechanism in molecular detail is unclear yet. However, the functional mechanism of human beta defensin type 2 (hBD-2) is known, which has a very similar secondary structure to hBD-3. To design novel drugs based on hBD-3, it is important to find out its functional mechanism. To fill this knowledge gap, we propose to conduct a comparative study investigating the binding structures of hBD-2 and hBD-3 with different explicit model bacterial lipid membranes using both solid-state NMR and molecular dynamics simulation methods, and evaluate the biological activity of hBDs through activity assays. The hypothesis is that the binding structure of hBD with lipids and its interaction with key molecules in the membranes determine its antibacterial mechanism. This project will help uncover the mysteries associated with hBD-3 disrupting bacterial cell membranes. Our methods applied will also pave the way for researching the mechanisms of other AMPs that disrupt bacterial lipid membranes.


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 = $597,254 )
2026	2026	UNIVERSITY OF RHODE ISLAND	75 LOWER COLLEGE RD RM 103	KINGSTON	RI	02881	WASHINGTON	USA	Biomedical Research and Research Training	000	1	4/17/2026	NEW	$597,254
														Subtotal = $597,254

Grand Total All Awards = $597,254

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Comparative Study on Human Beta Defensin Type 2 and 3 Interaction with Model Bacterial Lipid Membranes

Award Number: R15GM163254

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: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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