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Advancing Mass Spectrometry Analyses of Proteins, Assemblies, and Proteoforms

Award Number: R35GM145286
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Advancing Mass Spectrometry Analyses of Proteins, Assemblies, and Proteoforms - PROJECT SUMMARY/ABSTRACT Understanding cellular processes and pathways in depth requires methods that not only investigate the composition and arrangement of various protein assemblies, but that also elucidate their dynamics and functional regulation. Experimental strategies delivering structural information beyond primary sequence; i.e., higher-order structure and protein modifications, connect proteomics to structural biology in ways yielding potential insights into complex disease mechanisms. New techniques based on mass spectrometry (MS), native MS (i.e., measuring biomolecules in their native solution environment preserving ligand- and other molecular interactions), and top-down MS/proteomics will be advanced and applied to facilitate the characterization of proteins and protein assemblies. Coupling sensitive ionization, solution- and gas-phase separations, new electron-based dissociation methods (e.g., electron capture dissociation, ECD; electron ionization dissociation, EID) and other activation/dissociation techniques to ultra-high resolution mass spectrometry will provide an experimental platform for complete sequence and proteoform coverage. These advanced tools will be employed to characterize important biological complexes for which high-resolution structures have been difficult to obtain, including G-coupled protein receptors (GPCRs) and other membrane proteins. The exploration of links between post-translational modifications (PTMs) and proteoforms to the aggregation and toxicity of neurodegenerative diseases such as Alzheimer's disease (AD) will be furthered by our advanced MS methods. Our experimental strategies apply broadly and integrate with numerous biophysical techniques to enable the detailed structural study of large and complex molecular machines and to provide insights into their dynamics. Native top-down MS promises to advance structural biology and to hasten drug discovery and development. Improvements in MS-based technologies can advance our understanding of how proteins and protein machines drive biology.


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: 2026 ( Subtotal = $378,080 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	4/30/2026	NON-COMPETING CONTINUATION	$378,080
														Subtotal = $378,080

Issue Date FY: 2025 ( Subtotal = $378,080 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	4	4/15/2025	NON-COMPETING CONTINUATION	$378,080
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	11/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $378,080

Issue Date FY: 2024 ( Subtotal = $378,080 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	3	7/15/2024	NON-COMPETING CONTINUATION	$37,807
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	4/16/2024	NON-COMPETING CONTINUATION	$340,273
														Subtotal = $378,080

Issue Date FY: 2023 ( Subtotal = $378,080 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	4/6/2023	NON-COMPETING CONTINUATION	$378,080
														Subtotal = $378,080

Issue Date FY: 2022 ( Subtotal = $378,080 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	6/28/2022	NEW	$378,080
														Subtotal = $378,080

Grand Total All Awards = $1,890,400

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Advancing Mass Spectrometry Analyses of Proteins, Assemblies, and Proteoforms

Award Number: R35GM145286

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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