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Intracellular Signaling by Bacterial Chemoreceptors

Award Number: R01GM019559
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: 06/01/1991
PERIOD OF PERFORMANCE END DATE: 04/30/2027

Group Awards By:

View Award Description

Intracellular Signaling by Bacterial Chemoreceptors - Project Summary Chemotactic behaviors, movements toward or away from chemicals in an organism’s environment, play important roles in the lives of bacteria. Chemotaxis enables microbes to form communities such as biofilms, to find and colonize host organisms, and to successfully carry out complex, multi-host life cycles. Better understanding of how bacteria detect and respond to their chemical environment will play an important role in the development of new therapeutic strategies for preventing and treating bacterial infections. The long-term goal of this project is to elucidate, in molecular detail, the in vivo signaling mechanisms of the transmembrane receptors that mediate chemotactic behavior in E. coli, a model system for chemotaxis studies. The serine chemoreceptor Tsr forms stable ternary complexes with two cytoplasmic proteins – a histidine autokinase (CheA) and a scaffolding protein (CheW) that couples CheA activity to chemoreceptor control. These signaling complexes are organized into highly cooperative arrays, typically located at the cell poles, that detect chemical stimuli with high sensitivity over a wide range of concentrations. The overall objectives of the next project period are to elucidate the mechanisms of signal transmission through chemoreceptor molecules and how those ligand-induced conformational changes modulate CheA activity in receptor signaling complexes. Our overall working hypothesis about signal transmission within chemoreceptor molecules proposes that its structural subelements – external ligand-binding domain, transmembrane helices, HAMP and methylation helix bundles, and cytoplasmic hairpin tip that interacts directly with CheW and CheA – transmit and process sensory information through shifts in their dynamic behaviors and stabilities. Neighboring elements are coupled in opposition, such that destabilizing inputs to one element produce stabilizing responses in the other. The interplay of these opposing structural forces poises the receptor molecule to detect and respond to small stimulus inputs. The project will test these signaling ideas by exploiting in vivo crosslinking assays to detect and to trap different output-related structures in Tsr and CheA molecules. We will characterize the signaling properties of mutant or crosslinked proteins with in vivo serine dose-response assays based on Förster Resonance Energy Transfer (FRET). Collaborations with other groups will provide molecular dynamics simulations to assess the structural and dynamics changes in mutant signaling proteins and cryo- electron microscopy to examine structural features of mutant receptor arrays at enhanced resolution.


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 = $567,177 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	53	4/3/2026	NON-COMPETING CONTINUATION	$567,177
														Subtotal = $567,177

Issue Date FY: 2025 ( Subtotal = $577,181 )
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	52	4/1/2025	NON-COMPETING CONTINUATION	$577,181
														Subtotal = $577,181

Issue Date FY: 2024 ( Subtotal = $583,877 )
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	51	5/14/2024	NON-COMPETING CONTINUATION	$583,877
2024	2022	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	49	4/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $583,877

Issue Date FY: 2023 ( Subtotal = $582,466 )
2023	2023	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	002	50	5/16/2023	COMPETING CONTINUATION	$582,466
2023	2022	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	49	5/8/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2022	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	49	5/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $582,466

Issue Date FY: 2022 ( Subtotal = $574,736 )
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	49	2/21/2022	NON-COMPETING CONTINUATION	$508,279
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	002	49	6/20/2022	SUPPLEMENT FOR EXPANSION	$9,978
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	49	6/9/2022	NON-COMPETING CONTINUATION	$56,479
														Subtotal = $574,736

Issue Date FY: 2021 ( Subtotal = $564,758 )
2021	2021	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	48	2/11/2021	NON-COMPETING CONTINUATION	$564,758
														Subtotal = $564,758

Issue Date FY: 2020 ( Subtotal = $564,758 )
2020	2020	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	47	2/20/2020	NON-COMPETING CONTINUATION	$564,758
2020	2018	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	45	2/3/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $564,758

Issue Date FY: 2019 ( Subtotal = $564,758 )
2019	2019	UNIVERSITY OF UTAH, THE	201 S PRESIDENT CIRCLE RM 408	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	46	5/9/2019	COMPETING CONTINUATION	$564,758
2019	2018	UNIVERSITY OF UTAH, THE	201 S PRESIDENT CIRCLE RM 408	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	45	5/6/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $564,758

Issue Date FY: 2018 ( Subtotal = $535,725 )
2018	2018	UNIVERSITY OF UTAH, THE	201 S PRESIDENT CIRCLE RM 408	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	45	5/30/2018	NON-COMPETING CONTINUATION	$53,573
2018	2018	UNIVERSITY OF UTAH, THE	201 S PRESIDENT CIRCLE RM 408	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	45	2/1/2018	NON-COMPETING CONTINUATION	$482,152
														Subtotal = $535,725

Issue Date FY: 2017 ( Subtotal = $535,725 )
2017	2017	UNIVERSITY OF UTAH, THE	201 S PRESIDENT CIRCLE RM 408	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	44	6/20/2017	NON-COMPETING CONTINUATION	$53,573
2017	2017	UNIVERSITY OF UTAH, THE	201 S PRESIDENT CIRCLE RM 408	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	44	2/24/2017	NON-COMPETING CONTINUATION	$482,152
														Subtotal = $535,725

Issue Date FY: 2016 ( Subtotal = $535,725 )
2016	2016	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	43	2/11/2016	NON-COMPETING CONTINUATION	$535,725
2016	2015	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	42	2/10/2016	COMPETING CONTINUATION	$0
														Subtotal = $535,725

Issue Date FY: 2015 ( Subtotal = $535,725 )
2015	2015	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	42	3/17/2015	COMPETING CONTINUATION	$535,725
														Subtotal = $535,725

Issue Date FY: 2014 ( Subtotal = $511,188 )
2014	2014	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	41	5/1/2014	NON-COMPETING CONTINUATION	$511,188
														Subtotal = $511,188

Issue Date FY: 2013 ( Subtotal = $493,572 )
2013	2013	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	40	5/1/2013	NON-COMPETING CONTINUATION	$460,326
2013	2013	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	40	6/12/2013	NON-COMPETING CONTINUATION	$33,246
														Subtotal = $493,572

Issue Date FY: 2012 ( Subtotal = $512,902 )
2012	2012	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	39	5/2/2012	NON-COMPETING CONTINUATION	$512,902
														Subtotal = $512,902

Issue Date FY: 2011 ( Subtotal = $513,470 )
2011	2011	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	38	4/12/2011	COMPETING CONTINUATION	$513,470
														Subtotal = $513,470

Issue Date FY: 2010 ( Subtotal = $468,449 )
2010	2010	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	37	4/28/2010	NON-COMPETING CONTINUATION	$468,449
														Subtotal = $468,449

Issue Date FY: 2009 ( Subtotal = $735,589 )
2009	2009	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Trans-NIH Recovery Act Research Support	001	36	9/30/2009	SUPPLEMENT FOR EXPANSION	$276,192
2009	2009	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	36	4/15/2009	NON-COMPETING CONTINUATION	$459,397
														Subtotal = $735,589

Issue Date FY: 2008 ( Subtotal = $446,015 )
2008	2008	UNIVERSITY OF UTAH	201 SOUTH PRESIDENT`S CIRCLE	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	35	4/25/2008	NON-COMPETING CONTINUATION	$446,015
														Subtotal = $446,015

Grand Total All Awards = $12,336,181

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Intracellular Signaling by Bacterial Chemoreceptors

Award Number: R01GM019559

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: 06/01/1991

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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