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New approaches for chemical-genetic targeting of specific circuits and cell types in the mammalian brain

Award Number: RF1MH123224
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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New approaches for chemical-genetic targeting of specific circuits and cell types in the mammalian brain - The goal of this research is to establish new robust methods for manipulation of specific circuits and genetically defined neuron types in brains of model organisms with small molecules. While several chemical-genetic techniques are already available, these techniques have drawbacks that limit their utility. Our recent work demonstrates that these obstacles can be overcome by using a strategy for acute control of function of proteins of interest (POI) containing destabilizing domains (DD) with the inexpensive commercially available drug, TMP. This compound efficiently crosses the blood-brain barrier, stabilizes DD-POIs with a rapid time course, and does not produce undesired side effects by itself. Since DD tags can be attached to virtually any protein, TMP-inducible stabilization is applicable to a broad spectrum of experimental paradigms. We propose to generate mouse alleles and viral vectors encoding DD-POI fusions suitable for applications ranging from ultra-structural imaging to assessment of complex behaviors. We will develop tools for TMP-dependent recombination of DNA and genome editing (Aim1), acute labeling of behaviorally relevant neuron populations with a reporter compatible with optical imaging and electron microscopy (Aim2), and cell-type-specific control of neurotransmitter secretion (Aim3). Our collaborative team will demonstrate the advantages of these techniques by combining genomics, whole brain imaging, serial electron microscopy, electrophysiology, optogenetics and behavior. New tools will be compared side-by-side against existing technologies, and then distributed to the neuroscience community. We anticipate that these efforts will significantly benefit future studies of the normal brain and mechanisms underlying neurological diseases.


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 = $0 )
2025	2020	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	1	2/5/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	1	10/26/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	1	3/25/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	1	11/29/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $2,666,892 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	1	8/31/2020	NEW	$2,666,892
														Subtotal = $2,666,892

Grand Total All Awards = $2,666,892

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New approaches for chemical-genetic targeting of specific circuits and cell types in the mammalian brain

Award Number: RF1MH123224

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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