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Mapping the ciliary interactome, an extensive protein interaction network underlying human ciliopathies

Award Number: R01HD085901
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/05/2016
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Mapping the ciliary interactome, an extensive protein interaction network underlying human ciliopathies - SUMMARY Cilia are essential organelles, with functions ranging from cell-cell signaling to the generation of homeostatic fluid flow in tubular organs. Consequently, an array of human congenital diseases has been characterized as “ciliopathies,” because they share an etiology of defective cilia structure or function. Despite clear roles in the development of the central nervous system, limbs, axial skeleton, kidneys, airway, brain, and reproductive tracts, our understanding of the mechanisms that govern ciliogenesis and cilia-mediated developmental patterning remain incomplete, not least because hundreds of different proteins are required for proper cilia biogenesis and function, acting via an extensive interaction network containing diverse proteins of unknown function. We propose here to study several large multi-protein assemblies that are essential for proper cilia formation in order to determine the roles of these complexes in key steps in ciliogenesis, including recruitment of proteins to the basal body, intraflagellar transport and recruitment of specific intraflagellar cargoes. This grant combines directed mechanistic experiments, proteomics, 3D modeling, in vivo cell biology, and testing of human disease alleles in model organisms to understand mechanisms by which key ciliary proteins and their interaction partners effect proper cilia formation, and how specific mutations in these genes lead to birth defects. By focusing on proteins with demonstrated importance in development and disease, but for which no mechanism of action is yet known, experiments proposed here will provide important new breadth and depth to our understanding cilia-mediated developmental patterning and novel cell processes in ciliary biology. In turn, these findings should provide greater insight to a range of congenital diseases ranging from the relatively mild Oral-Facial-Digital syndrome to the wholly lethal Short Rib Polydactyly.


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 = $578,838 )
2025	2025	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	10	6/20/2025	NON-COMPETING CONTINUATION	$578,838
														Subtotal = $578,838

Issue Date FY: 2024 ( Subtotal = $573,050 )
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	9	6/18/2024	NON-COMPETING CONTINUATION	$573,050
														Subtotal = $573,050

Issue Date FY: 2023 ( Subtotal = $578,838 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	8	6/27/2023	NON-COMPETING CONTINUATION	$578,838
														Subtotal = $578,838

Issue Date FY: 2022 ( Subtotal = $578,838 )
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	002	7	6/17/2022	NON-COMPETING CONTINUATION	$578,838
2022	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	001	6	12/10/2021	COMPETING CONTINUATION	$273,683
2022	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	5	12/7/2021	NON-COMPETING CONTINUATION	-$273,683
														Subtotal = $578,838

Issue Date FY: 2021 ( Subtotal = $578,838 )
2021	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	6	4/22/2021	COMPETING CONTINUATION	$578,838
														Subtotal = $578,838

Issue Date FY: 2020 ( Subtotal = $509,504 )
2020	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	5	6/16/2020	NON-COMPETING CONTINUATION	$509,504
														Subtotal = $509,504

Issue Date FY: 2019 ( Subtotal = $512,820 )
2019	2019	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	4	6/21/2019	NON-COMPETING CONTINUATION	$512,820
														Subtotal = $512,820

Issue Date FY: 2018 ( Subtotal = $516,044 )
2018	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	3	7/9/2018	NON-COMPETING CONTINUATION	$516,044
														Subtotal = $516,044

Issue Date FY: 2017 ( Subtotal = $580,988 )
2017	2017	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	000	2	7/14/2017	NON-COMPETING CONTINUATION	$519,170
2017	2017	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Child Health and Human Development Extramural Research	001	2	8/18/2017	SUPPLEMENT FOR EXPANSION	$61,818
														Subtotal = $580,988

Issue Date FY: 2016 ( Subtotal = $535,957 )
2016	2016	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Child Health and Human Development Extramural Research	000	1	9/4/2016	NEW	$535,957
														Subtotal = $535,957

Grand Total All Awards = $5,543,715

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Mapping the ciliary interactome, an extensive protein interaction network underlying human ciliopathies

Award Number: R01HD085901

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/05/2016

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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