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Metalloregulation by MerR and Fur Protein Families

Award Number: R01GM038784
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: 07/01/1987
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Metalloregulation by MerR and Fur Protein Families - PROJECT SUMMARY There is a growing need in the biomedical research community to understand the fundamental roles and mechanisms that regulate inorganic chemistry involved in cellular physiology. While many of these metals have been labeled as ‘trace elements,’ from a cellular point of view this is a misnomer: the intracellular concentrations of zinc and iron are routinely maintained at much higher levels (i.e., 0.6 mM). These insights, as well as the emerging literature linking metal physiology to many human disease states, underscore the importance of establishing the fundamental principles, general pathways, and macromolecular mechanisms employed to manage the large numbers of metal ions required for optimal health of a cell. Our approach to the discovery of these novel pathways and principles involves mechanistic and structural characterization of metal receptors that switch on and off genes in a metal dependent manner and that subsequently control the activity of cellular machinery that maintains metal concentrations within narrow ranges. There are three principle thrusts in this proposal: a) determining how zinc regulons are controlled by metalloregulatory switching events through newly discovered protein-RNA interactions; b) establishing mechanisms for how copper, zinc, and mercury sensing metalloregulatory switches control the topology of DNA within an RNA polymerase promoter complex, and then applying these insights to the development of new types of metal ion sensors, and c) developing quantitative metallomic methods that enable researchers across the biomedical research continuum to address the question of how quantitative inorganic phenotypes vary across cells involved in commensal or pathophysiological interactions with the human host. Overall, these aims focus on resolving fundamental questions about the structures, functions, and molecular mechanisms of wide-spread families of metal-sensing metalloregulatory proteins. The proposed experimental approach will employ x-ray crystallography, biophysical methods, single particle cryo-electron microscopy, proteomic, bioanalytical, spectroscopic and bioinformatic methods to understand the pathways that microorganisms use to respond to changing metal ion availability in the growth media, or in the mammalian host. The effects of these biophysical switching mechanisms on intracellular metal physiology will then be examined using novel single cell analytical and imaging methods coupled with traditional batch quantitative measurements with the overarching goal of establishing general principles and mechanisms that control metal ion homeostasis in normal and disease states.


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 = $314,000 )
2025	2025	HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES	426 AUDITORIUM RD	EAST LANSING	MI	48824	INGHAM	USA	Biomedical Research and Research Training	000	32	8/25/2025	COMPETING CONTINUATION	$314,000
														Subtotal = $314,000

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	31	4/30/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	31	12/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $376,753 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	31	1/24/2020	NON-COMPETING CONTINUATION	$339,078
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	31	3/3/2020	NON-COMPETING CONTINUATION	$37,675
														Subtotal = $376,753

Issue Date FY: 2019 ( Subtotal = $376,753 )
2019	2019	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	30	11/14/2018	NON-COMPETING CONTINUATION	$376,753
														Subtotal = $376,753

Issue Date FY: 2018 ( Subtotal = $376,753 )
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	29	11/30/2017	NON-COMPETING CONTINUATION	$339,078
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	29	5/23/2018	NON-COMPETING CONTINUATION	$37,675
														Subtotal = $376,753

Issue Date FY: 2017 ( Subtotal = $402,334 )
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	002	28	12/27/2016	COMPETING CONTINUATION	$402,334
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	004	28	9/5/2017	COMPETING CONTINUATION	$35,108
2017	2015	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	27	12/22/2016	NON-COMPETING CONTINUATION	$0
2017	2015	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	003	27	9/5/2017	SUPPLEMENT FOR EXPANSION	-$35,108
2017	2015	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	27	12/23/2016	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $402,334

Issue Date FY: 2015 ( Subtotal = $579,280 )
2015	2015	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	27	6/16/2015	SUPPLEMENT FOR EXPANSION	$225,000
2015	2015	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	27	3/19/2015	NON-COMPETING CONTINUATION	$354,280
														Subtotal = $579,280

Issue Date FY: 2014 ( Subtotal = $354,280 )
2014	2014	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	26	3/19/2014	NON-COMPETING CONTINUATION	$354,280
														Subtotal = $354,280

Issue Date FY: 2013 ( Subtotal = $341,820 )
2013	2013	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	001	25	6/25/2013	NON-COMPETING CONTINUATION	$23,024
2013	2013	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	25	3/13/2013	NON-COMPETING CONTINUATION	$318,796
														Subtotal = $341,820

Issue Date FY: 2012 ( Subtotal = $393,265 )
2012	2012	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Biomedical Research and Research Training	000	24	6/1/2012	COMPETING CONTINUATION	$393,265
														Subtotal = $393,265

Issue Date FY: 1999 ( Subtotal = $249,768 )
1999	1999	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Cell Biology and Biophysics Research	000	13	6/10/1999	NON-COMPETING CONTINUATION	$249,768
														Subtotal = $249,768

Issue Date FY: 1998 ( Subtotal = $242,593 )
1998	1998	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Cell Biology and Biophysics Research	000	12	5/29/1998	NON-COMPETING CONTINUATION	$242,593
														Subtotal = $242,593

Grand Total All Awards = $4,007,599

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Metalloregulation by MerR and Fur Protein Families

Award Number: R01GM038784

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: 07/01/1987

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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