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Microtubule dynamics and error correction

Award Number: R01GM145567
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: 06/07/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Microtubule dynamics and error correction - Modified Project Summary/Abstract Section The broad goal of this project is to understand how force generation by kinesin-related motors and dynamic microtubules controls the fidelity of chromosome segregation. Both microtubules and motors represent excellent targets for anti-cancer drugs but to make wise choices for developing therapeutics it is necessary to understand their contribution to cell division in detail. MCAK/Kif2C is a MT depolymerizing kinesin that controls MT length within the spindle and supresses chromosome instability (CIN). Using CRISPR/Cas9 engineered cells, rapamycin-dependent relocalization and long-term live imaging we have pinpointed the precise contribution that this protein makes to enhance the fidelity of chromosome segregation which will enable us to understand why this protein rescues CIN in tumorigenic cells and its future potential as a therapeutic target. MCAK/Kif2C is also strongly associated with centrosomes where it has the potential to suppress MT outgrowth and influence centrosome separation. We have identified two other poorly studied centrosome-associated kinesins, Kif25 and Kif9, that function in centrosome cohesion and centrosome satellite positioning respectively and that also impact centrosome separation and positioning. Altered centrosome positioning in cell culture has limited effects on cell viability. However, Both Kif9 and Kif25 are widely expressed in vertebrates. Because Kif25, in particular, is most highly expressed in brain it affords an opportunity to investigate the role of centrosome cohesion in vertebrate development and neural stem cell division using morpholinos directed against Kif25 introduced into early zebrafish embryos. We aim to use live and fixed-cell imaging tools and transgenic cell lines to investigate, with precision, the contribution that these kinesins make to preserving the fidelity of the genome and to long-term cell fate. Ultimately this knowledge base can be leveraged to develop new therapies that target kinesin enzymology or MT dynamics.


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 = $341,384 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	4	2/20/2025	NON-COMPETING CONTINUATION	$341,384
														Subtotal = $341,384

Issue Date FY: 2024 ( Subtotal = $379,315 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	3	7/11/2024	NON-COMPETING CONTINUATION	$37,931
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	3	2/9/2024	NON-COMPETING CONTINUATION	$341,384
														Subtotal = $379,315

Issue Date FY: 2023 ( Subtotal = $629,243 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	2	2/7/2023	NON-COMPETING CONTINUATION	$379,315
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	2	5/19/2023	SUPPLEMENT FOR EXPANSION	$249,928
														Subtotal = $629,243

Issue Date FY: 2022 ( Subtotal = $379,315 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	001	1	8/26/2022	NEW	$0
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Biomedical Research and Research Training	000	1	6/7/2022	NEW	$379,315
														Subtotal = $379,315

Grand Total All Awards = $1,729,257

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Microtubule dynamics and error correction

Award Number: R01GM145567

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: 06/07/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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