Wednesday, October 9, 2024 10/9/2024

Molecular Mechanisms of Membrane Transport

Award Number: R01GM035215
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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View Award Abstract

Active membrane transport is central to many cell processes, including the acquisition of nutrients, the establishment of ion-gradients, the regulation of osmotic balance, ATP synthesis, and apoptosis. The proposed work will address key questions regarding the mechanisms of nutrient uptake in Escherichia coli, and it will address questions regarding the structure and organization of these proteins in the bacterial outer-membrane. In E. coli, a range of nutrients are transported by specific outer-membrane proteins that derive energy by coupling to the inner- membrane protein TonB. These TonB-dependent transporters include BtuB, which is responsible for vitamin B12 transport, and FhuA, FecA and FepA, which are responsible for the transport of various forms of chelated iron. TonB-dependent transporters are abundant in Gram negative bacteria, and they are critical to the proper functioning of the human microbiome where they are responsible for the acquisition and initial processing of some carbohydrates. They are also essential for the success of many bacterial pathogens, such as those that result in meningitis, cholera, pertussis and dysentery; and because TonB-dependent transport is unique to bacteria, it is thought to be a target for the development of new classes of antibiotics. High-resolution crystallographic models have been obtained for approximately two dozen TonB- dependent transporters; however, the mechanism by which transport takes place is unclear. One difficulty is that structural and biophysical studies in-vitro have never been made on TonB- dependent transport proteins that are known to be active. The proposed work will test models for the molecular mechanisms of transport and examine structural states that are only observed in cells. The role of lipopolysaccharide in altering transport protein structure will also be examined. The proposed work will employ site-directed spin labeling and EPR spectroscopy where novel approaches have been developed to perform pulse experiments, such as double electron-electron resonance, in intact E. coli. In the outer-membrane, proteins are sequestered into domains or islands, which are thought to drive the turnover of outer-membrane proteins in bacteria. EPR will be used in E. coli to characterize the protein-protein interactions that drive domain formation and define the supramolecular structure of the outer-membrane.


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 = $422,261 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	003	34	6/17/2024	NON-COMPETING CONTINUATION	$34,931
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	004	34	8/21/2024	SUPPLEMENT FOR EXPANSION	$72,947
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	002	34	3/15/2024	NON-COMPETING CONTINUATION	$314,383
2024	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	33	3/1/2024	COMPETING CONTINUATION	$219,121
2024	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	32	3/1/2024	NON-COMPETING CONTINUATION	-$219,121
														Subtotal = $422,261

Issue Date FY: 2023 ( Subtotal = $349,314 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	33	6/29/2023	COMPETING CONTINUATION	$349,314
2023	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	32	6/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $349,314

Issue Date FY: 2022 ( Subtotal = $326,958 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	32	6/27/2022	NON-COMPETING CONTINUATION	$32,696
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	32	12/22/2021	NON-COMPETING CONTINUATION	$294,262
														Subtotal = $326,958

Issue Date FY: 2021 ( Subtotal = $327,731 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	31	3/2/2021	NON-COMPETING CONTINUATION	$32,774
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	31	12/23/2020	NON-COMPETING CONTINUATION	$294,957
														Subtotal = $327,731

Issue Date FY: 2020 ( Subtotal = $428,466 )
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	30	12/19/2019	NON-COMPETING CONTINUATION	$295,619
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	002	30	8/13/2020	SUPPLEMENT FOR EXPANSION	$100,000
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	30	2/28/2020	NON-COMPETING CONTINUATION	$32,847
														Subtotal = $428,466

Issue Date FY: 2019 ( Subtotal = $329,167 )
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	29	3/19/2019	COMPETING CONTINUATION	$329,167
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	003	29	7/22/2019	COMPETING CONTINUATION	$42,162
2019	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	002	28	7/22/2019	NON-COMPETING CONTINUATION	-$42,162
2019	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	28	3/14/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $329,167

Issue Date FY: 2017 ( Subtotal = $315,142 )
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	28	6/14/2017	NON-COMPETING CONTINUATION	$315,142
														Subtotal = $315,142

Issue Date FY: 2016 ( Subtotal = $315,392 )
2016	2016	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	27	6/23/2016	NON-COMPETING CONTINUATION	$315,392
														Subtotal = $315,392

Issue Date FY: 2015 ( Subtotal = $428,235 )
2015	2015	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	26	6/30/2015	SUPPLEMENT FOR EXPANSION	$112,600
2015	2015	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	26	6/26/2015	NON-COMPETING CONTINUATION	$315,635
														Subtotal = $428,235

Issue Date FY: 2014 ( Subtotal = $315,871 )
2014	2014	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	25	8/29/2014	COMPETING CONTINUATION	$315,871
														Subtotal = $315,871

Issue Date FY: 2012 ( Subtotal = $286,885 )
2012	2012	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	24	3/16/2012	NON-COMPETING CONTINUATION	$28,688
2012	2012	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	24	11/17/2011	NON-COMPETING CONTINUATION	$258,197
														Subtotal = $286,885

Issue Date FY: 2011 ( Subtotal = $285,751 )
2011	2011	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	23	6/20/2011	NON-COMPETING CONTINUATION	$25,977
2011	2011	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	23	12/15/2010	NON-COMPETING CONTINUATION	$259,774
														Subtotal = $285,751

Issue Date FY: 2010 ( Subtotal = $284,901 )
2010	2010	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	22	11/25/2009	NON-COMPETING CONTINUATION	$259,000
2010	2010	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	22	5/13/2010	NON-COMPETING CONTINUATION	$25,901
														Subtotal = $284,901

Issue Date FY: 2009 ( Subtotal = $514,431 )
2009	2009	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Trans-NIH Recovery Act Research Support	002	21	9/30/2009	SUPPLEMENT FOR EXPANSION	$228,959
2009	2009	UNIVERSITY OF VIRGINIA	P.O. BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	001	21	11/21/2008	COMPETING CONTINUATION	$285,472
2009	2007	UNIVERSITY OF VIRGINIA	PO BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	20	11/21/2008	NON-COMPETING CONTINUATION	$0
														Subtotal = $514,431

Issue Date FY: 2007 ( Subtotal = $229,816 )
2007	2007	UNIVERSITY OF VIRGINIA	PO BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	20	7/20/2007	NON-COMPETING CONTINUATION	$229,816
														Subtotal = $229,816

Issue Date FY: 2006 ( Subtotal = $236,942 )
2006	2006	UNIVERSITY OF VIRGINIA	PO BOX 400195	CHARLOTTESVILLE	VA	22904	CHARLOTTESVILLE CITY	USA	Biomedical Research and Research Training	000	19	7/19/2006	NON-COMPETING CONTINUATION	$236,942
														Subtotal = $236,942

Grand Total All Awards = $6,691,164

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Molecular Mechanisms of Membrane Transport

Award Number: R01GM035215

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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