Saturday, December 21, 2024 12/21/2024

Molecular Mechanism of the Cytoplasmic Dynein-Dynactin Motor Complex

Award Number: R01GM098469
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Title: Molecular Mechanism of the Cytoplasmic Dynein-Dynactin Motor Complex Our long-term goal is to elucidate the molecular mechanism of the cytoplasmic dynein-dynactin motor complex, and to define the molecular bases of dynein-related diseases in humans. The microtubule motor cytoplasmic dynein, in cooperation with its regulatory proteins, drives several processes essential to embryonic development, including neuronal proliferation, neuronal migration, and the transport of numerous intracellular cargoes. Thus, it is not surprising dysfunction of dynein contributes to birth defects. A striking example is lissencephaly (LIS), a rare, but devastating brain malformation. Variants of this diseases are caused by loss or mutation of the dynein regulator Lis1. In lissencephaly, neurons fail to migrate properly during development and affected infants’ brains lack the normal gyral folding pattern and layering of the cerebral cortex. These children suffer untreatable epilepsy and severe psychomotor retardation, often dying in the first year of life. Unfortunately, mechanistic insights into dynein function and its regulation by Lis1 are limited, hampering our ability to understand the molecular basis for LIS, and other dynein-linked human diseases. In this proposal, we will combine single-molecule fluorescence and optical tweezers-based force measurements with innovative protein engineering to determine how cytoplasmic dynein in complex with its activator dynactin and the cargo adaptor bicaudal D (BicD), is regulated by Lis1. We will decipher how Lis1 regulates the motion and force generation of the dynein-dynactin-BicD (DDB) motor complex, and determine the effects of human disease mutations on Lis1-DDB function. These studies will provide a new understanding of dynein-linked diseases, and elucidate molecular targets for future therapeutic interventions.


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 = $379,680 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	14	3/19/2024	NON-COMPETING CONTINUATION	$341,713
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	001	14	7/17/2024	NON-COMPETING CONTINUATION	$37,967
														Subtotal = $379,680

Issue Date FY: 2023 ( Subtotal = $603,235 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	003	13	7/31/2023	SUPPLEMENT FOR EXPANSION	$223,555
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	002	13	3/3/2023	NON-COMPETING CONTINUATION	$379,680
2023	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	001	12	11/21/2022	COMPETING CONTINUATION	$74,062
2023	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	11	11/21/2022	NON-COMPETING CONTINUATION	-$74,062
														Subtotal = $603,235

Issue Date FY: 2022 ( Subtotal = $490,655 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	001	12	5/12/2022	COMPETING CONTINUATION	$379,680
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	002	12	8/22/2022	SUPPLEMENT FOR EXPANSION	$110,975
2022	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	11	5/4/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $490,655

Issue Date FY: 2021 ( Subtotal = $359,050 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	11	4/1/2021	NON-COMPETING CONTINUATION	$359,050
														Subtotal = $359,050

Issue Date FY: 2020 ( Subtotal = $572,972 )
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	10	3/12/2020	NON-COMPETING CONTINUATION	$359,050
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	001	10	8/10/2020	SUPPLEMENT FOR EXPANSION	$213,922
														Subtotal = $572,972

Issue Date FY: 2019 ( Subtotal = $359,050 )
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	005	9	3/26/2019	NON-COMPETING CONTINUATION	$359,050
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	001	8	2/7/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$111,796
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	007	7	5/23/2019	COMPETING CONTINUATION	-$10,623
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	006	7	4/17/2019	COMPETING CONTINUATION	$100
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	004	7	3/8/2019	COMPETING CONTINUATION	$150,358
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	003	7	2/10/2019	COMPETING CONTINUATION	$201
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	7	2/6/2019	COMPETING CONTINUATION	-$262,254
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	008	8	5/23/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$10,623
2019	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	002	6	2/10/2019	NON-COMPETING CONTINUATION	-$201
														Subtotal = $359,050

Issue Date FY: 2018 ( Subtotal = $374,050 )
2018	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	001	7	5/3/2018	COMPETING CONTINUATION	$374,050
2018	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Biomedical Research and Research Training	000	6	4/30/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $374,050

Issue Date FY: 2016 ( Subtotal = $317,300 )
2016	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Biomedical Research and Research Training	002	6	8/2/2016	NON-COMPETING CONTINUATION	$317,300
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Biomedical Research and Research Training	001	5	12/11/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$290,858
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Biomedical Research and Research Training	000	4	12/10/2015	NON-COMPETING CONTINUATION	-$290,858
														Subtotal = $317,300

Issue Date FY: 2015 ( Subtotal = $317,300 )
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Biomedical Research and Research Training	000	4	8/5/2015	NON-COMPETING CONTINUATION	$317,300
														Subtotal = $317,300

Issue Date FY: 2014 ( Subtotal = $317,300 )
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Biomedical Research and Research Training	000	3	7/15/2014	NON-COMPETING CONTINUATION	$317,300
														Subtotal = $317,300

Issue Date FY: 2013 ( Subtotal = $306,195 )
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Biomedical Research and Research Training	000	2	7/24/2013	NON-COMPETING CONTINUATION	$306,195
														Subtotal = $306,195

Issue Date FY: 2012 ( Subtotal = $296,932 )
2012	2012	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Biomedical Research and Research Training	000	1	7/12/2012	NEW	$296,932
														Subtotal = $296,932

Grand Total All Awards = $4,693,719

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Molecular Mechanism of the Cytoplasmic Dynein-Dynactin Motor Complex

Award Number: R01GM098469

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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