Sunday, October 1, 2023 10/1/2023

Structure and Function of the Acetylcholine Receptor

Award Number: R01NS031744
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT- Members of the nicotinic acetylcholine receptor (AChR) gene family mediate synaptic transmission throughout the central and peripheral nervous systems. The AChR family is part of the superfamily of pentameric ligand-gated ion channels (pLGICs) that also includes receptors activated by the neurotransmitters serotonin, gamma-amino-butyric acid, and glycine. Collectively, the pLGIC superfamily mediates the majority of neurotransmission occurring on the millisecond time frame. The over-arching goal of our research is to understand mechanisms by which AChRs transduce a chemical stimulus into an electrical response, a process central to understanding disorders of excitability caused by inherited mutations of AChR, and to developing drugs to treat such disorders. Toward this end, the proposed studies address key gaps in our understanding of chemo-electrical transduction by the AChR spanning from basic to translational science. The first aim is to delineate biophysical and structural mechanisms by which ion transport through the AChR channel is coupled to gating of the channel between inactive and active states. The second aim is to elucidate biophysical and structural mechanisms by which changes in extracellular calcium, a major regulatory ion, modulate the strength of signaling by the major type of AChR in the brain. The third aim is to delineate mechanisms by which inherited mutations in the major type of brain AChR cause epilepsy, and develop mechanism-based therapeutic solutions. To achieve these aims, we employ a multidisciplinary approach that includes functional measurements from single AChR molecules, computational methods to simulate atomic scale interactions between AChRs and physiological modulators, and atomic-scale structure determination of normal and diseased AChRs. The overall studies will resolve key gaps in understanding AChR signaling mechanisms central to physiology, pharmacology, and pathophysiology. The insights will apply not only to AChRs from muscle and brain studied herein, but also to other members of the pLGIC superfamily.


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: 2023 ( Subtotal = $520,299 )
2023	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	29	4/28/2023	NON-COMPETING CONTINUATION	$520,299


Issue Date FY: 2022 ( Subtotal = $520,299 )
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	28	4/14/2022	NON-COMPETING CONTINUATION	$520,299


Issue Date FY: 2021 ( Subtotal = $520,165 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	27	4/15/2021	NON-COMPETING CONTINUATION	$520,165
2021	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	26	11/10/2020	COMPETING CONTINUATION	$1,809
2021	2017	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	11/10/2020	NON-COMPETING CONTINUATION	-$1,809


Issue Date FY: 2020 ( Subtotal = $534,537 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	26	6/30/2020	COMPETING CONTINUATION	$534,537


Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	5/20/2019	NON-COMPETING CONTINUATION	$0


Issue Date FY: 2017 ( Subtotal = $478,334 )
2017	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	4/14/2017	NON-COMPETING CONTINUATION	$430,500
2017	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	25	5/25/2017	NON-COMPETING CONTINUATION	$47,834


Issue Date FY: 2016 ( Subtotal = $478,334 )
2016	2016	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	4/8/2016	NON-COMPETING CONTINUATION	$478,334


Issue Date FY: 2015 ( Subtotal = $478,334 )
2015	2015	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	4/16/2015	NON-COMPETING CONTINUATION	$478,334


Issue Date FY: 2014 ( Subtotal = $478,334 )
2014	2014	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	22	6/23/2014	COMPETING CONTINUATION	$478,334
2014	2012	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	12/30/2013	NON-COMPETING CONTINUATION	$0
2014	2012	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	21	6/20/2014	NON-COMPETING CONTINUATION	$0


Issue Date FY: 2012 ( Subtotal = $610,843 )
2012	2012	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	2/15/2012	NON-COMPETING CONTINUATION	$610,843


Issue Date FY: 2011 ( Subtotal = $602,531 )
2011	2011	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	20	6/21/2011	NON-COMPETING CONTINUATION	$43,145
2011	2011	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	2/14/2011	NON-COMPETING CONTINUATION	$559,386


Issue Date FY: 2010 ( Subtotal = $600,020 )
2010	2010	MAYO CLINIC ROCHESTER	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	2/4/2010	NON-COMPETING CONTINUATION	$600,020


Issue Date FY: 2009 ( Subtotal = $590,552 )
2009	2009	MAYO CLINIC ROCHESTER	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	18	4/7/2009	NON-COMPETING CONTINUATION	$59,055
2009	2009	MAYO CLINIC ROCHESTER	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	2/23/2009	NON-COMPETING CONTINUATION	$531,497


Issue Date FY: 2008 ( Subtotal = $522,954 )
2008	2008	MAYO CLINIC ROCHESTER	200 FIRST STREET, S. W.	ROCHESTER	MN	55901	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	9/8/2008	COMPETING CONTINUATION	$522,954


Issue Date FY: 2000 ( Subtotal = $392,498 )
2000	2000	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Biological Basis Research in the Neurosciences	000	9	9/4/2000	NON-COMPETING CONTINUATION	$392,498


Issue Date FY: 1999 ( Subtotal = $427,402 )
1999	1999	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Biological Basis Research in the Neurosciences	000	8	7/28/1999	NON-COMPETING CONTINUATION	$377,402
1999	1999	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Biological Basis Research in the Neurosciences	001	8	9/16/1999	SUPPLEMENT FOR EXPANSION	$50,000


Issue Date FY: 1998 ( Subtotal = $364,933 )
1998	1998	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Biological Basis Research in the Neurosciences	001	6	5/18/1998	SUPPLEMENT FOR EXPANSION	$2,046
1998	1998	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Biological Basis Research in the Neurosciences	000	7	9/9/1998	NON-COMPETING CONTINUATION	$362,887


Grand Total All Awards = $8,120,369

Sum of Action Amount is $8,120,369;

Grand Total = $8,120,369

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Structure and Function of the Acetylcholine Receptor

Award Number: R01NS031744

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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