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Interrogating the function of motile ciliated cells in spinal curvature using a zebrafish model of adolescent idiopathic scoliosis

Award Number: F32AR078002
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Summary Adolescent Idiopathic Scoliosis (AIS) is a prevalent developmental condition (affecting ~3% of the population) of unknown origin, characterized by abnormal, three-dimensional spinal curvatures that occur during phases of adolescent growth. Recently, numerous zebrafish models of AIS have emerged as powerful tools for addressing etiology of the condition and characterizing the fundamental biological mechanisms that facilitate spinal straightness. However, the varied genetic underpinnings of these models, the diversity of their spinal curvatures, and complexity of the growing spine – a tissue that provides an interface for tissues of the skeletal, muscular, and nervous systems – means that an ability to perform quantitative, phenotypic analysis on micro-computed tomography (microCT) data is a critical barrier to our ability to describe the pathways that mediate and maintain spinal straightness. The objectives of this proposal are to address this barrier to progress by applying a new modality of quantitative, multiscale phenomics analysis to zebrafish models of AIS, which will allow us to address fundamental questions about the developmental mechanisms that mediate and maintain spinal straightness. Recent work by my advisor has shown that zebrafish with mutations that paralyze motile cilia during windows of juvenile growth develop three-dimensional spinal curvatures recapitulating AIS. Our Central Hypothesis is that motile cilia of the spinal canal ependyma are critical signaling devices in the local `perception' and mechanical correction of spinal straightness and curvature. We intend to challenge these ideas through three Specific Aims: (1) Test the spatial requirement for motile cilia during spinal straightness. (2) Identify which specific motile ciliated cell types are critical for a straight spine. (3) Test the requirement for CSF-contacting neurons in a mechanical axis downstream of motile cilia. Research Design: We will use our quantitative, multiscale phenomics platform to evaluate the impact of genetic manipulations involving either global, partial, or cell-type specific inactivation of cilia motility on spinal straightness. This will inform our understanding of how motile cilia relay information to their local tissue environments, contribute to our fundamental understanding of how the spine “knows” to grow straight, and inform our future directions in the research and treatment of AIS.


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: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	10/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $70,692 )
2023	2023	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	8/21/2023	NON-COMPETING CONTINUATION	$70,692
														Subtotal = $70,692

Issue Date FY: 2022 ( Subtotal = $67,582 )
2022	2022	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	8/3/2022	NON-COMPETING CONTINUATION	$67,582
														Subtotal = $67,582

Issue Date FY: 2021 ( Subtotal = $65,994 )
2021	2021	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	3/29/2021	NEW	$0
2021	2021	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/29/2021	NEW	$65,994
														Subtotal = $65,994

Grand Total All Awards = $204,268

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Interrogating the function of motile ciliated cells in spinal curvature using a zebrafish model of adolescent idiopathic scoliosis

Award Number: F32AR078002

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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