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Chemi-Knock: Achieving rapidly inducible loss-of-function in live animal brains during memory consolidation

Award Number: R21MH138991
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Chemi-Knock: Achieving rapidly inducible loss-of-function in live animal brains during memory consolidation - PROJECT SUMMARY Memory consolidation is an important process in memory retention, whereby short-term memories are transformed into long-term ones. Memory retention is facilitated when novel or salient experiences occur within 1-2 hours before or after memory encoding. Novelty-induced memory consolidation relies on the locus coeruleus-hippocampus pathway and involves the de novo synthesis of an–as–yet–unidentified group of proteins known as plasticity-related proteins (PRPs) in the hippocampus. These PRPs are thought to play a critical role in memory consolidation by stabilizing synaptic plasticity. However, the precise mechanism through which these newly synthesized PRPs facilitate the consolidation of synaptic plasticity and memory in the hippocampus remains unclear. This uncertainty primarily arises from the limited availability of loss-of-function techniques capable of perturbing the function of the target PRP with a minute temporal resolution and selectively within this memory process. This project aims to develop innovative molecular tool, using chemical-based manipulation, that enable the rapid and precise inactivation of endogenous target proteins in specific cell types during memory consolidation without genetic modification. Specifically, upon a chemical trigger, our new tool is designed to relocate a target PRP from its active site to other subcellular locations within a timeframe of minutes. This relocation can be achieved in specific neuron types in the hippocampus of freely moving rats undergoing memory tasks. To demonstrate the utility of this tool, we have selected activity-regulated cytoskeleton associated protein (ARC), one of the major PRPs, as a model target. Success in this endeavor will not only shed light on the elusive molecular mechanisms of memory consolidation by identifying key PRPs but also potentially reveal new pharmacological targets to improve memory retention. Moreover, the flexible and modular nature of this genetically encoded tool opens the door to its use in a broad range of biological applications beyond memory research.


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 = $427,625 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Mental Health Research Grants	000	1	5/19/2026	NEW	$427,625
														Subtotal = $427,625

Grand Total All Awards = $427,625

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Chemi-Knock: Achieving rapidly inducible loss-of-function in live animal brains during memory consolidation

Award Number: R21MH138991

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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