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Next-generation Mass Spectrometry Technologies for Integrated Structural Proteomics- Renewal

Award Number: R01GM095832
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: 04/01/2011
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Next-generation Mass Spectrometry Technologies for Integrated Structural Proteomics- Renewal - Project Summary Within each organism proteins are at work carrying out activities which impact every aspect of cellular function. A key factor in achieving such a wide range of protein functions involves the post translational modifications and sequence modifications that act to produce a vast array of functional protein states form a single gene product. Such proteoforms are further coupled directly to the 3D structures of the biomolecules created, which are further recruited into a wide array of dynamic multi-protein machines. Directly assessing the structures of these assembly states, along with the proteoforms that they contain is crucial for understanding human disease. Despite this, most structures remain unknown and are refractory to current technologies, and their proteoform compliment remains opaque. Standard structural biology approaches (X-ray, NMR, and Cryo-EM), while highly successful, require pure samples in large quantities, painstakingly optimized to produce monodisperse protein populations in every respect, and to remove spectral background. Furthermore, transient and polydisperse assemblies that exist within complex mixtures cannot be analyzed. Mass spectrometry (MS) approaches developed to attack this challenging problem can overcome many of these obstacles. While these tools are undergoing a rapid development phase, they currently lack the ability to discreetly assess the influence of proteoforms on multiprotein organization. Consequently there is a need to develop improved MS approaches capable of simultaneously assessing the structural proteome, enabling links between proteoform composition and 3D structure for the host of dynamic, heterogeneous macromolecular complexes of clear biomedical importance. This renewal application seeks to construct new, innovative MS techniques that 1) utilize new classes of chemical tagging reagents and mixed tagging methodologies to promote comprehensive sequencing of intact multi-protein complexes, 2) leverage next-generation cyclic ion mobility-mass spectrometry (IM-MS) technology to produce high-definition collision induced unfolding (CIU) and native top-down sequencing methods that enable improved identification of proteoforms within assemblies, 3) produce new techniques for the direct sequencing of membrane protein complexes, including laser-based activation of detergent clusters for improved data quality, 4) combine electron capture dissociation (ECD) with CIU for on-the-fly annotation of fingerprint data, and 5) automated methods for protein derivatization and clean-up compatible with native proteomics. This technology will be brought to bear to discover the structures of a series of selected proteoforms and complexes, each linked to human disease.


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 = $0 )
2025	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	12	8/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $541,257 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	12	9/19/2024	NON-COMPETING CONTINUATION	$541,257
														Subtotal = $541,257

Issue Date FY: 2023 ( Subtotal = $541,257 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	001	11	8/24/2023	NON-COMPETING CONTINUATION	$541,257
2023	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	10	5/2/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $541,257

Issue Date FY: 2022 ( Subtotal = $541,257 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	004	10	8/18/2022	NON-COMPETING CONTINUATION	$541,257
2022	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	003	9	7/6/2022	COMPETING CONTINUATION	-$41,158
2022	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	001	9	11/28/2021	COMPETING CONTINUATION	$41,158
2022	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	006	9	8/29/2022	COMPETING CONTINUATION	$42,404
2022	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	8	11/28/2021	NON-COMPETING CONTINUATION	-$41,158
2022	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	005	8	8/29/2022	NON-COMPETING CONTINUATION	-$42,404
2022	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	002	8	7/6/2022	NON-COMPETING CONTINUATION	$41,158
														Subtotal = $541,257

Issue Date FY: 2021 ( Subtotal = $541,257 )
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	002	9	6/21/2021	COMPETING CONTINUATION	$541,257
2021	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	8	2/19/2021	NON-COMPETING CONTINUATION	$0
2021	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	001	8	6/18/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $541,257

Issue Date FY: 2019 ( Subtotal = $531,190 )
2019	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	8	1/18/2019	NON-COMPETING CONTINUATION	$531,190
														Subtotal = $531,190

Issue Date FY: 2018 ( Subtotal = $556,557 )
2018	2018	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	7	1/17/2018	NON-COMPETING CONTINUATION	$500,901
2018	2018	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	001	7	5/7/2018	NON-COMPETING CONTINUATION	$55,656
														Subtotal = $556,557

Issue Date FY: 2017 ( Subtotal = $573,465 )
2017	2017	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	001	6	8/4/2017	NON-COMPETING CONTINUATION	$57,345
2017	2017	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	6	1/18/2017	NON-COMPETING CONTINUATION	$516,120
														Subtotal = $573,465

Issue Date FY: 2016 ( Subtotal = $588,096 )
2016	2016	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	002	5	2/8/2016	COMPETING CONTINUATION	$588,096
2016	2014	Regents of the University of Michigan	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	481091287	WASHTENAW	USA	Biomedical Research and Research Training	001	4	2/3/2016	NON-COMPETING CONTINUATION	$0
2016	2014	Regents of the University of Michigan	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	481091287	WASHTENAW	USA	Biomedical Research and Research Training	000	4	12/14/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $588,096

Issue Date FY: 2014 ( Subtotal = $307,865 )
2014	2014	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	4	5/6/2014	NON-COMPETING CONTINUATION	$307,865
														Subtotal = $307,865

Issue Date FY: 2013 ( Subtotal = $297,097 )
2013	2013	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	001	3	6/10/2013	NON-COMPETING CONTINUATION	$20,013
2013	2013	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	3	3/25/2013	NON-COMPETING CONTINUATION	$277,084
														Subtotal = $297,097

Issue Date FY: 2012 ( Subtotal = $307,876 )
2012	2012	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	2	4/6/2012	NON-COMPETING CONTINUATION	$307,876
														Subtotal = $307,876

Issue Date FY: 2011 ( Subtotal = $453,299 )
2011	2011	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Biomedical Research and Research Training	000	1	3/31/2011	NEW	$453,299
														Subtotal = $453,299

Grand Total All Awards = $5,780,473

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Next-generation Mass Spectrometry Technologies for Integrated Structural Proteomics- Renewal

Award Number: R01GM095832

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: 04/01/2011

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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