Sunday, August 17, 2025 8/17/2025

Metastable Crystallins: Structure and Stabilization

Award Number: R01EY023219
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2013
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Metastable Crystallins: Structure and Stabilization - Abstract α-Crystallin is a complex macromolecule that accounts for nearly 40% of the adult lens proteins. The chaperone-like activity of α-crystallin, which was discovered nearly three decades ago, is implicated as a key component in the maintenance of lens transparency by suppression of crystallin aggregation. It was found that the deletion of 21-28 and 54-61 regions of αB-crystallin leads to increased chaperone-like activity (activation, gain of function). Understanding the molecular organization and properties of crystallin subunits in activated chaperones would help answer questions on how α-crystallin chaperone-like activity might be harnessed and manipulated for the development of protein-based therapeutics. It is hypothesized that the increased αB- crystallin chaperone-like activity in deletion mutants stems from new type of oligomers where subunit–subunit interactions lead to the exposure of “cryptic” chaperone sites in the native oligomers. Studies show a recombinant αB-crystallin expressed after deleting either 54-61 or 21-28 and 54-61 sequences (resulting in a protein designated as αBΔ54-61 and αBΔ21-28,Δ54-61) was found to form smaller oligomers than the wild- type protein but to show up to ~25-fold increase in chaperone-like activity. The experiments proposed in this proposal will uncover the molecular changes that drive the increased chaperone-like activity in αBΔ21-28,Δ54- 61 and αBΔ54-61. The aims of the application are 1) Uncover the molecular changes in the activated αB- crystallins, (αBΔ54-61 and αBΔ21-28,Δ54-61), 2) determine the biological implications of enhanced chaperone-like activity of engineered proteins in the cell culture and whole lens culture system. Novel crosslinker(s) will be used to gain fresh insights into the “cryptic” chaperone sites getting exposed in the activated crystallin. The studies will also make use of site-directed mutagenesis and mass spectrometric analysis to uncover the molecular changes at subunit interaction level in activated oligomers. To see whether the activated αB-crystallin can be exploited to protect cells from oxidative injury, the effects of stress-inducing agents such as H2O2 and sodium iodate will be investigated in HEK293 and ARPE-19 cells in presence of activated crystallins. Further, the ability of activated chaperones to suppress aggregation and toxicity of fibril- forming β-amyloid will be investigated both in vitro and ex-vivo. The long-term goals of the studies are to understand the structure–function relationship of activated αB-crystallins and develop crystallin proteins that have therapeutic value in protein conformational diseases and oxidative stress conditions.


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 = $462,921 )
2025	2025	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	12	4/18/2025	NON-COMPETING CONTINUATION	$462,921
														Subtotal = $462,921

Issue Date FY: 2024 ( Subtotal = $462,921 )
2024	2024	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	001	11	6/3/2024	NON-COMPETING CONTINUATION	$462,921
2024	2021	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	9	5/2/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $462,921

Issue Date FY: 2023 ( Subtotal = $462,921 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	001	10	5/26/2023	COMPETING CONTINUATION	$462,921
2023	2021	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	9	5/22/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $462,921

Issue Date FY: 2021 ( Subtotal = $375,875 )
2021	2021	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	9	6/16/2021	NON-COMPETING CONTINUATION	$375,875
														Subtotal = $375,875

Issue Date FY: 2020 ( Subtotal = $706,758 )
2020	2020	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	001	8	8/19/2020	SUPPLEMENT FOR EXPANSION	$319,258
2020	2020	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	8	6/22/2020	NON-COMPETING CONTINUATION	$387,500
														Subtotal = $706,758

Issue Date FY: 2019 ( Subtotal = $457,468 )
2019	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	001	7	6/26/2019	NON-COMPETING CONTINUATION	$387,500
2019	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Dietary Supplement Research Program	002	7	9/16/2019	SUPPLEMENT FOR EXPANSION	$69,968
2019	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	5	1/30/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $457,468

Issue Date FY: 2018 ( Subtotal = $387,500 )
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	001	6	8/23/2018	COMPETING CONTINUATION	$387,500
2018	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	5	8/20/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $387,500

Issue Date FY: 2017 ( Subtotal = $391,718 )
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	001	5	8/21/2017	NON-COMPETING CONTINUATION	$39,172
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Vision Research	000	5	4/19/2017	NON-COMPETING CONTINUATION	$352,546
														Subtotal = $391,718

Issue Date FY: 2016 ( Subtotal = $391,718 )
2016	2016	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Vision Research	000	4	4/22/2016	EXTENSION WITH OR WITHOUT FUNDS	$391,718
														Subtotal = $391,718

Issue Date FY: 2015 ( Subtotal = $438,494 )
2015	2015	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Vision Research	000	3	4/13/2015	NON-COMPETING CONTINUATION	$383,883
2015	2015	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Vision Research	001	3	8/27/2015	SUPPLEMENT FOR EXPANSION	$54,611
														Subtotal = $438,494

Issue Date FY: 2014 ( Subtotal = $383,884 )
2014	2014	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Vision Research	000	2	4/23/2014	NON-COMPETING CONTINUATION	$383,884
														Subtotal = $383,884

Issue Date FY: 2013 ( Subtotal = $479,566 )
2013	2013	CURATORS OF THE UNIVERSITY OF MISSOURI	310 Jesse Hall	Columbia	MO	65211	BOONE	USA	Vision Research	000	1	5/1/2013	NEW	$479,566
														Subtotal = $479,566

Grand Total All Awards = $5,401,744

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Metastable Crystallins: Structure and Stabilization

Award Number: R01EY023219

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2013

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer