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Development of high-dose time-resolved X-ray footprinting technologies to enable detailed structural and kinetics information to be obtained for challenging biological problems

Award Number: R01GM126218
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract The overarching goal in this project, both in the funded award and in this renewal, is to advance the structural biology method of X-ray footprinting mass spectrometry (XFMS) in capability and accessibility such that it becomes a premiere biophysical tool for biomedical investigators around the country. XFMS is a solution state method used to map solvent accessible regions in macromolecules on a timescale of microseconds, yielding information on conformation, protein-protein dynamics, and bound water location and dynamics. It has been used to obtain useful structural information on a diverse range biological systems, from small proteins to large complexes, as well as membrane proteins, and for mapping interaction regions in antibody-target complexes. As part of the original award, we made substantial progress towards our main goal by developing a unique high-throughput and automated XFMS instrument, enabling use of the method to researchers nationwide. In this proposed renewal, we plan to build on this success to implement new capabilities in keeping with the original goal of the grant. Specifically, we plan to integrate fluorescence and Raman spectroscopies, fast mixing with jet delivery capability, and size exclusion directly inline with the XFMS instrument. The integration of these technologies into the XFMS instrument will enable even more challenging biological systems to be studied using the method. While the new specific aims are ambitious, they build naturally from our proven track record in developing complex instrumentation and the successful research team we built during the first grant period. Proof of principle for these technologies is presented, along with preliminary data, and the proposal outlines the significant technical challenges involved and how they will be overcome. The resulting technologies will be a significant gain to the biomedical research community and will be used to meet the increasing demand for access to the XFMS method.


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 = $422,230 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	7	5/15/2024	NON-COMPETING CONTINUATION	$422,230
														Subtotal = $422,230

Issue Date FY: 2023 ( Subtotal = $424,470 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	002	6	6/14/2023	NON-COMPETING CONTINUATION	$424,470
2023	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	001	5	6/8/2023	COMPETING CONTINUATION	$11,974
2023	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	4	6/8/2023	NON-COMPETING CONTINUATION	-$11,974
														Subtotal = $424,470

Issue Date FY: 2022 ( Subtotal = $425,897 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	001	5	5/30/2022	COMPETING CONTINUATION	$425,897
2022	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	4	5/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $425,897

Issue Date FY: 2021 ( Subtotal = $362,948 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	4	12/7/2020	NON-COMPETING CONTINUATION	$326,653
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	001	4	3/2/2021	NON-COMPETING CONTINUATION	$36,295
														Subtotal = $362,948

Issue Date FY: 2020 ( Subtotal = $362,948 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	3	12/19/2019	NON-COMPETING CONTINUATION	$326,653
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	001	3	3/10/2020	NON-COMPETING CONTINUATION	$36,295
														Subtotal = $362,948

Issue Date FY: 2019 ( Subtotal = $362,948 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	2	1/9/2019	NON-COMPETING CONTINUATION	$362,948
														Subtotal = $362,948

Issue Date FY: 2018 ( Subtotal = $663,556 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	001	1	9/4/2018	SUPPLEMENT FOR EXPANSION	$300,608
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	1	12/25/2017	NEW	$362,948
														Subtotal = $663,556

Grand Total All Awards = $3,024,997

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Development of high-dose time-resolved X-ray footprinting technologies to enable detailed structural and kinetics information to be obtained for challenging biological problems

Award Number: R01GM126218

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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