Wednesday, April 24, 2024 4/24/2024

Structure-function studies of visual arrestin

Award Number: R01EY011500
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY We propose to elucidate the molecular mechanisms of arrestin-1 interactions with rhodopsin, which significantly contribute to exquisitely regulated and precisely timed function of photoreceptor cells, using the combination of novel cutting-edge biophysical methods and in vivo experiments. We will compare the shape of the complex of arrestin-1 with rhodopsin using long-range distance measurements between selected points in arrestin-1 and rhodopsin with pulse EPR technique DEER. We will explore the conformation of arrestin-bound rhodopsin and compare it to the conformation of free light-activated rhodopsin and rhodopsin in complex with transducing to determine whether particular conformation states of rhodopsin (a model GPCR) predispose it to interact with G protein and arrestin. This is hypothesized in the field to be the basis of biased GPCR signaling. We will determine the biological role of arrestin-1 self-association in photoreceptors in vivo, which is currently unknown. Finally, we will test novel compensational approach to gene therapy of gain-of-function rhodopsin mutations using engineered enhanced arrestin-1 mutants capable of shutting off rhodopsin signaling independently of its phosphorylation. Proposed studies will significantly improve our understanding of photoreceptor physiology and advance our progress towards gene therapy of gain-of-function rhodopsin mutations. Due to high conservation of mechanics of GPCR regulation, mechanistic studies of arrestin-1 binding to rhodopsin will have broader implications, improving our understanding of the molecular basis of the function of other arrestin subtypes. Proposed studies will shed new light on many aspects of cell signaling. Our strategic goal is to gain sufficient understanding of protein-protein interactions that govern cell signaling to construct mutants with desired functional characteristics for research and therapeutic purposes.


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: 2023 ( Subtotal = $599,889 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	000	26	5/9/2023	NON-COMPETING CONTINUATION	$599,889
														Subtotal = $599,889

Issue Date FY: 2022 ( Subtotal = $581,892 )
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	000	25	6/21/2022	NON-COMPETING CONTINUATION	$581,892
														Subtotal = $581,892

Issue Date FY: 2021 ( Subtotal = $581,585 )
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	000	24	4/19/2021	NON-COMPETING CONTINUATION	$581,585
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	001	24	4/22/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $581,585

Issue Date FY: 2020 ( Subtotal = $647,262 )
2020	2020	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	000	23	4/21/2020	COMPETING CONTINUATION	$597,997
2020	2020	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	001	23	8/28/2020	SUPPLEMENT FOR EXPANSION	$49,265
														Subtotal = $647,262

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	000	22	8/26/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $520,275 )
2018	2018	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	000	22	4/27/2018	NON-COMPETING CONTINUATION	$520,275
														Subtotal = $520,275

Issue Date FY: 2017 ( Subtotal = $520,275 )
2017	2017	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	000	21	3/27/2017	NON-COMPETING CONTINUATION	$468,556
2017	2017	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Vision Research	001	21	6/28/2017	NON-COMPETING CONTINUATION	$51,719
														Subtotal = $520,275

Issue Date FY: 2016 ( Subtotal = $520,275 )
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	20	4/14/2016	NON-COMPETING CONTINUATION	$520,275
														Subtotal = $520,275

Issue Date FY: 2015 ( Subtotal = $520,275 )
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	001	19	4/16/2015	COMPETING CONTINUATION	$520,275
2015	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	18	4/13/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $520,275

Issue Date FY: 2013 ( Subtotal = $534,906 )
2013	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	18	7/4/2013	NON-COMPETING CONTINUATION	$534,906
														Subtotal = $534,906

Issue Date FY: 2012 ( Subtotal = $563,060 )
2012	2012	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	17	7/23/2012	NON-COMPETING CONTINUATION	$563,060
														Subtotal = $563,060

Issue Date FY: 2011 ( Subtotal = $563,060 )
2011	2011	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	16	7/18/2011	NON-COMPETING CONTINUATION	$563,060
														Subtotal = $563,060

Issue Date FY: 2010 ( Subtotal = $561,012 )
2010	2010	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	15	7/13/2010	NON-COMPETING CONTINUATION	$561,012
														Subtotal = $561,012

Issue Date FY: 2009 ( Subtotal = $550,465 )
2009	2009	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	001	14	7/2/2009	COMPETING CONTINUATION	$550,465
2009	2008	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Family Violence Prevention and Services/Domestic Violence Shelter and Supportive Services	000	13	7/2/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $550,465

Issue Date FY: 2008 ( Subtotal = $526,927 )
2008	2008	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Family Violence Prevention and Services/Domestic Violence Shelter and Supportive Services	000	13	4/17/2008	NON-COMPETING CONTINUATION	$526,927
														Subtotal = $526,927

Issue Date FY: 2007 ( Subtotal = $522,019 )
2007	2007	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Family Violence Prevention and Services/Domestic Violence Shelter and Supportive Services	000	12	3/16/2007	NON-COMPETING CONTINUATION	$522,019
														Subtotal = $522,019

Issue Date FY: 2006 ( Subtotal = $509,669 )
2006	2006	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Family Violence Prevention and Services/Domestic Violence Shelter and Supportive Services	000	11	3/31/2006	NON-COMPETING CONTINUATION	$509,669
														Subtotal = $509,669

Issue Date FY: 2005 ( Subtotal = $506,732 )
2005	2005	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Family Violence Prevention and Services/Domestic Violence Shelter and Supportive Services	000	10	4/28/2005	COMPETING CONTINUATION	$506,732
														Subtotal = $506,732

Issue Date FY: 2004 ( Subtotal = $265,125 )
2004	2004	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	9	3/18/2004	NON-COMPETING CONTINUATION	$265,125
														Subtotal = $265,125

Issue Date FY: 2003 ( Subtotal = $319,315 )
2003	2003	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	001	8	9/19/2003	SUPPLEMENT FOR EXPANSION	$54,190
2003	2003	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	8		NON-COMPETING CONTINUATION	$265,125
														Subtotal = $319,315

Issue Date FY: 2002 ( Subtotal = $265,125 )
2002	2002	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Vision Research	000	7	9/26/2002	NON-COMPETING CONTINUATION	$265,125
														Subtotal = $265,125

Issue Date FY: 2001 ( Subtotal = $293,300 )
2001	2001	SUN HEALTH RESEARCH INSTITUTE	POST OFFICE BOX 1278	SUN CITY	AZ	85372	MARICOPA	USA	Vision Research	000	5	5/3/2001	COMPETING CONTINUATION	$293,300
														Subtotal = $293,300

Grand Total All Awards = $11,166,429

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Structure-function studies of visual arrestin

Award Number: R01EY011500

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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