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Mutant Tubulins Confer Resistance to Pathological Tau

Award Number: R00AG073455
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Mutant Tubulins Confer Resistance to Pathological Tau - Project Summary/Abstract Pathological tau is present in a number of age-related diseases (tauopathies) including Alzheimer's Disease (AD). With a rising aged population the prevalence of these diseases will become an enormous healthcare, economic and social burden. To-date there are no clinically proven disease altering treatments. Recently, we have discovered mutant tubulin modifies tauopathy-like phenotypes in transgenic C. elegans models, reducing human tau-induced motility deficits and neurodegeneration. We hypothesize that mutant tubulin ameliorates tau-induced phenotypes in C. elegans by altering tau-microtubule interactions. To test our hypothesis we propose to 1) use C. elegans to determine if the level of tubulin suppression is based in tubulin expression level 2) use reconstituted in vitro systems to test whether tubulin mutations affect tau- microtubule interactions and 3) use mammalian primary neurons to test whether mutant tubulin impacts microtubule properties and function. The proposed projects will elucidate the mechanisms of mutant tubulin suppression of tau induced-pathology and tau-microtubule interactions. Additionally, this work will contribute greater understanding of the cytoskeleton in neurodegenerative disease. My goal is to develop a career as a principal investigator devoted to the discovery of the molecular mechanisms underpinning tauopathies and the roles the cytoskeletal network play in neurodegeneration. To accomplish this, my training plan focuses on 1) expanding my technical toolkit to incorporate biophysical approaches and live cell imaging 2) gaining greater knowledge in the biology of aging 3) improving skills in laboratory leadership and expanding my professional network. The University of Washington and the Veterans Affairs Puget Sound Health Care System share an abundance of researchers interested in Alzheimer's and other neurodegenerative conditions. There are substantial intellectual resources such as seminars, journal clubs and meetings that create numerous opportunities broaden my perspective through interactions with the medical and scientific community in AD-related research.


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 = $244,021 )
2025	2025	SEATTLE INSTITUTE FOR BIOMEDICAL AND CLINICAL RESEARCH	1660 S COLUMBIAN WAY	SEATTLE	WA	98108	KING	USA	Aging Research	000	5	7/11/2025	NON-COMPETING CONTINUATION	$244,021
														Subtotal = $244,021

Issue Date FY: 2024 ( Subtotal = $301,759 )
2024	2024	SEATTLE INSTITUTE FOR BIOMEDICAL AND CLINICAL RESEARCH	1660 S COLUMBIAN WAY	SEATTLE	WA	98108	KING	USA	Aging Research	003	4	7/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2024	SEATTLE INSTITUTE FOR BIOMEDICAL AND CLINICAL RESEARCH	1660 S COLUMBIAN WAY	SEATTLE	WA	98108	KING	USA	Aging Research	002	4	6/25/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$249,000
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Aging Research	000	3	2/22/2024	EXTENSION WITH OR WITHOUT FUNDS	$249,000
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Aging Research	001	3	6/21/2024	EXTENSION WITH OR WITHOUT FUNDS	-$249,000
2024	2024	SEATTLE INSTITUTE FOR BIOMEDICAL AND CLINICAL RESEARCH	1660 S COLUMBIAN WAY	SEATTLE	WA	98108	KING	USA	Aging Research	004	4	8/8/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$52,759
														Subtotal = $301,759

Grand Total All Awards = $545,780

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Mutant Tubulins Confer Resistance to Pathological Tau

Award Number: R00AG073455

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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