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Patterning acentrosomal microtubule arrays

Award Number: R35GM133573
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: 08/12/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2029

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Patterning acentrosomal microtubule arrays - Abstract The microtubule cytoskeleton supports cell-division, cellular morphology and intracellular cargo transport. While the centrosome is a major site of microtubule nucleation in dividing cells, many differentiated cells harbor acentrosomal microtubule arrays. Prominent examples include germline cells, plant epidermis, epithelia and neurons. To understand cellular differentiation, it is crucial to learn how acentrosomal array architecture is set up to achieve a specific pattern of polymer numbers, length and distribution that would support specialized cellular functions. My laboratory studies the patterning of acentrosomal microtubules and its effect on cargo transport in C. elegans. We developed imaging tools and algorithms that allow an unprecedented level of analysis of microtubule organization in vivo and are compatible with live-imaging of cargo transport. We conducted unbiased screens to uncover novel microtubule regulators and are using genetics, imaging, and biochemical methods to understand their mechanisms. In parallel, we are investigating the biological significance of microtubule array patterns by examining the effects of these regulators on long-range intracellular transport. This proposal details our recent progress, including the finding of dynein regulation by an immotile kinesin at the microtubule minus-end, the identification of a protein that promotes nucleation with -tubulin, and uncovering a mechano-transduction pathway that adjusts microtubule positioning in response to stretch. For the next period we propose work that follows up on microtubule nucleation and minus-end protection, the distribution of microtubule polymers, and the regulation of cargo transport by MAPs. Given the fundamental roles of microtubules in differentiated cells, we expect this work to provide meaningful insights in the broad fields of cellular differentiation, cytoskeleton and transport. The involvement of cytoskeletal defects in numerous disorders suggests that in the long-term, our studies will help to shed light on mechanisms of cellular dysfunction that occurs during disease.


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 = $479,050 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	005	6	5/15/2025	COMPETING CONTINUATION	$226
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	002	6	12/24/2024	COMPETING CONTINUATION	$479,050
2025	2023	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	5	12/16/2024	NON-COMPETING CONTINUATION	$0
2025	2023	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	003	5	5/15/2025	NON-COMPETING CONTINUATION	-$171
2025	2023	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	001	5	12/17/2024	SUPPLEMENT FOR EXPANSION	$0
2025	2023	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	004	5	5/15/2025	SUPPLEMENT FOR EXPANSION	-$55
														Subtotal = $479,050

Issue Date FY: 2023 ( Subtotal = $553,648 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	001	5	6/29/2023	SUPPLEMENT FOR EXPANSION	$134,900
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	5	6/28/2023	NON-COMPETING CONTINUATION	$418,748
														Subtotal = $553,648

Issue Date FY: 2022 ( Subtotal = $418,748 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	4	7/21/2022	NON-COMPETING CONTINUATION	$418,748
														Subtotal = $418,748

Issue Date FY: 2021 ( Subtotal = $418,748 )
2021	2021	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	3	7/26/2021	NON-COMPETING CONTINUATION	$418,748
														Subtotal = $418,748

Issue Date FY: 2020 ( Subtotal = $418,748 )
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	2	7/30/2020	NON-COMPETING CONTINUATION	$418,748
														Subtotal = $418,748

Issue Date FY: 2019 ( Subtotal = $418,748 )
2019	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	1	8/12/2019	NEW	$418,748
														Subtotal = $418,748

Grand Total All Awards = $2,707,690

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Patterning acentrosomal microtubule arrays

Award Number: R35GM133573

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: 08/12/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2029

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