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Elucidating the neural specific functions of the RNA-binding protein Caper in neural development and neurodegeneration

Award Number: R15NS104976
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Elucidating the neural specific functions of the RNA-binding protein Caper in neural development and neurodegeneration - Project Summary/Abstract Post-transcriptional gene regulation is a fundamental mechanism that helps regulate the development and healthy aging of the nervous system. Mutations that disrupt the function of RNA-binding proteins (RBPs), which regulate post-transcriptional gene regulation, have increasingly been implicated in neurological disorders including amyotrophic lateral sclerosis, Fragile X Syndrome, and spinal muscular atrophy. Interestingly, although the majority of RBPs are expressed widely within diverse tissue types, the nervous system is often particularly sensitive to their dysfunction. The long-term goal of this project is to begin to elucidate how aberrant RNA regulation that results from the dysfunction of ubiquitously expressed RBPs, leads to tissue specific pathologies that underlie neurological diseases. To this end, the highly conserved splicing factor Caper will be used as a model. Caper is widely expressed throughout development and is required for the development of Drosophila sensory and motor neurons. Furthermore, caper dysfunction causes neurodegeneration and results in adult locomotor deficits. Though little is known about the function of the human caper ortholog, RBM39, it is expressed within the nervous system suggesting its neural functions may be conserved. The research proposed within this application will test the hypothesis that Caper regulates RNA targets in a combinatorial manner within neuronal cells by participating in specific ribonucleoprotein complexes (RNPs) within the nervous system. We have identified proteins encoding RBPs that interact with Caper only within the brain, along with neural specific Caper target RNAs. Using the highly tractable model, Drosophila, tissue specific molecular genetic manipulations will be used in conjunction with biochemistry to determine the extent to which Caper functions combinatorially with these RBPs to direct neurogenesis and protect the aging brain from neurodegeneration. Furthermore, we will further characterize the neurodegenerative phenotypes associated with caper dysfunction to determine which cell types are undergoing cell death in the aging brain. Since aberrant RNA regulation has emerged as a common theme in various neurodegenerative and neurodevelopmental disorders, the knowledge gained from this study has broad implications for understanding and treating neurological 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 = $0 )
2025	2022	THE REGENTS OF THE UNIVERSITY OF COLORADO	1420 AUSTIN BLUFFS PKWY	COLORADO SPRINGS	CO	80918	EL PASO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	9/23/2025	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = -$1,363 )
2024	2018	THE REGENTS OF THE UNIVERSITY OF COLORADO	1420 AUSTIN BLUFFS PKWY	COLORADO SPRINGS	CO	80918	EL PASO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	10/1/2023	NEW	-$1,363
														Subtotal = -$1,363

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	REGENTS OF THE UNIVERSITY OF COLORADO	1420 AUSTIN BLUFFS PARKWAY	COLORADO SPRINGS	CO	80918	EL PASO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	8/17/2023	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $438,000 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	1420 AUSTIN BLUFF PKWY CH209	COLORADO SPRINGS	CO	80918	EL PASO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	9/27/2022	COMPETING CONTINUATION	$438,000
2022	2018	REGENTS OF THE UNIVERSITY OF COLORADO, THE	1420 AUSTIN BLUFF PKWY CH209	COLORADO SPRINGS	CO	80918	EL PASO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/27/2022	NEW	$0
														Subtotal = $438,000

Issue Date FY: 2018 ( Subtotal = $432,000 )
2018	2018	REGENTS OF THE UNIVERSITY OF COLORADO, THE	1420 AUSTIN BLUFF PKWY CH209	COLORADO SPRINGS	CO	80918	EL PASO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/11/2018	NEW	$432,000
														Subtotal = $432,000

Grand Total All Awards = $868,637

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Elucidating the neural specific functions of the RNA-binding protein Caper in neural development and neurodegeneration

Award Number: R15NS104976

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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