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Mechanisms of non-centrosomal microtubule-organizing center functions

Award Number: R01GM139971
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: 03/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Mechanisms of non-centrosomal microtubule-organizing center functions - Centrosomes are the major and best-understood microtubule-organizing centers (MTOCs) in animal cells, yet in most differentiated cells non-centrosomal MTOCs (ncMTOCs) redirect MT organization instead of the centrosome. The sheer diversity of ncMTOCs reflects the different functions of various cell types and the subcellular locations and mechanisms of MT assembly that serve those roles. Understanding the molecular architecture of these ncMTOCs, the mechanisms of MT assembly they employ, and the functions they serve to the diverse cell types they serve remains an important frontier in cell biology and disease. The few ncMTOCs that have been deciphered reveal architectures and mechanisms of MT assembly as diverse as the functions they serve for the varied cell types. In this proposal we expand on a project to define the functions of a perinuclear ncMTOC in fat body cells which serves the cell by providing nuclear positioning and is essential for retrograde endosomal trafficking to support the vital secretory roles of this cell type. We will determine the unique molecular mechanisms of MT assembly by two distinct protein complexes that control MT assembly/nucleation from this ncMTOC. Specifically, this proposal aims to further define the structure of the fat body ncMTOC on the nuclear surface, and to define the mechanisms of MT assembly by Patronin and Ninein and how they cooperate with the microtubule polymerase Minispindles (Msps) and other partners to nucleate MTs. The outcomes of this project will be a definitive and novel understanding of the molecular and physiological functions of the fat body ncMTOC, revealing potentially novel disease etiologies for the proteins involved and the processes that they regulate. Moreover, as a molecular MT nucleation paradigm that is independent of the widespread microtubule nucleator gamma-tubulin, we will define at least one new mechanism to generate MTs at MTOCs.


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 = -$6 )
2026	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	4	6/11/2026	NON-COMPETING CONTINUATION	-$6
														Subtotal = -$6

Issue Date FY: 2024 ( Subtotal = $303,632 )
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	4	12/29/2023	NON-COMPETING CONTINUATION	$273,269
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	4	6/19/2024	NON-COMPETING CONTINUATION	$30,363
														Subtotal = $303,632

Issue Date FY: 2023 ( Subtotal = $503,632 )
2023	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	3	5/22/2023	SUPPLEMENT FOR EXPANSION	$200,000
2023	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	3	2/8/2023	NON-COMPETING CONTINUATION	$303,632
														Subtotal = $503,632

Issue Date FY: 2022 ( Subtotal = $303,632 )
2022	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	2	1/14/2022	NON-COMPETING CONTINUATION	$273,268
2022	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	2	8/3/2022	NON-COMPETING CONTINUATION	$30,364
														Subtotal = $303,632

Issue Date FY: 2021 ( Subtotal = $347,433 )
2021	2021	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	1	2/26/2021	NEW	$347,433
														Subtotal = $347,433

Grand Total All Awards = $1,458,323

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Mechanisms of non-centrosomal microtubule-organizing center functions

Award Number: R01GM139971

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: 03/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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