Wednesday, February 5, 2025 2/5/2025

Microtubule Dynamics and Axon Growth

Award Number: R01NS028785
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Neurons are terminally post-mitotic cells that use their microtubule arrays not for cell division but rather as architectural elements required for the elaboration of elongated axons and dendrites. In addition to acting as compression-bearing struts that provide for the shape of the neuron, microtubules also act as directional railways for organelle transport. Microtubules in the axon are nearly uniformly oriented, with the plus ends of the microtubules directed away from the cell body (“plus-ends-out”). Preservation of this microtubule pattern is crucial for the normal functioning of an axon throughout the life of the neuron. This microtubule polarity pattern is also important for distinguishing features of the axon from the dendrite, as dendrites of vertebrate neurons have a mixed pattern of microtubule polarity orientation. Long-standing questions in cellular neuroscience are how the plus-end-out polarity pattern of microtubules arises in the axon, how axons maintain this pattern during the life of the neuron and how flaws arising from plastic events in the life of the neuron are repaired. This competing renewal builds on a mechanism called “polarity sorting,” in which microtubules are organized according to their polarity orientation via their transport by molecular motor proteins. Specifically, the investigators hypothesize that in the case of the healthy axon, microtubules are transported with plus-ends leading, so that plus-end-out microtubules move forward down the axon while minus-end-out microtubules are transported back to the cell body to clear them from the axon. If not for this clearing mechanism, minus-end- out microtubules would accumulate in the axon and corrupt its polarity pattern. The proposed experiments will first test the polarity-sorting hypothesis. Experiments will then be conducted to test the hypothesis that two minus-end-directed molecular motor proteins, namely cytoplasmic dynein and KIFC1, share the responsibility of polarity sorting microtubules in the axon. Finally, studies will be conducted to identify the structures against which the molecular motors generate forces to transport microtubules in the axon. Mobile microtubules are generally quite short, and are hypothesized to move against either long microtubules or actin bundles, depending on the particular motor protein. Computational modeling will add additional rigor to the project, especially in terms of explaining why the axon’s microtubule polarity pattern is corrupted when various molecular players are manipulated. The experiments will utilize contemporary live-cell imaging techniques with unprecedented documentation of the polarity orientation of mobile microtubules in the axon, together with methods for acutely inhibiting molecular motor proteins. The work has relevance to potential treatments for diseases of the nervous system that may corrupt the microtubule polarity pattern of the axon.


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 = $0 )
2025	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	33	12/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	33	9/29/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $340,161 )
2021	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	33	7/27/2021	NON-COMPETING CONTINUATION	$340,161
														Subtotal = $340,161

Issue Date FY: 2020 ( Subtotal = $340,161 )
2020	2020	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	32	8/4/2020	NON-COMPETING CONTINUATION	$340,161
														Subtotal = $340,161

Issue Date FY: 2019 ( Subtotal = $340,161 )
2019	2019	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	31	8/7/2019	NON-COMPETING CONTINUATION	$340,161
														Subtotal = $340,161

Issue Date FY: 2018 ( Subtotal = $340,161 )
2018	2018	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	30	7/26/2018	NON-COMPETING CONTINUATION	$340,161
2018	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	29	2/14/2018	COMPETING CONTINUATION	$164,870
2018	2016	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	28	2/14/2018	EXTENSION WITH OR WITHOUT FUNDS	-$164,870
														Subtotal = $340,161

Issue Date FY: 2017 ( Subtotal = $340,161 )
2017	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	29	7/28/2017	COMPETING CONTINUATION	$340,161
2017	2016	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	28	4/12/2017	EXTENSION WITH OR WITHOUT FUNDS	$148,836
2017	2015	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	27	4/12/2017	NON-COMPETING CONTINUATION	-$148,836
														Subtotal = $340,161

Issue Date FY: 2016 ( Subtotal = $424,348 )
2016	2016	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	27	3/10/2016	SUPPLEMENT FOR EXPANSION	$30,508
2016	2016	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	27	4/11/2016	SUPPLEMENT FOR EXPANSION	$30,508
2016	2016	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	27	4/4/2016	SUPPLEMENT FOR EXPANSION	-$30,508
2016	2016	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	28	8/3/2016	EXTENSION WITH OR WITHOUT FUNDS	$393,840
														Subtotal = $424,348

Issue Date FY: 2015 ( Subtotal = $336,030 )
2015	2015	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	27	7/29/2015	NON-COMPETING CONTINUATION	$336,030
														Subtotal = $336,030

Issue Date FY: 2014 ( Subtotal = $332,669 )
2014	2014	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	26	7/16/2014	NON-COMPETING CONTINUATION	$332,669
														Subtotal = $332,669

Issue Date FY: 2013 ( Subtotal = $336,030 )
2013	2013	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	4/1/2013	COMPETING CONTINUATION	$336,030
														Subtotal = $336,030

Issue Date FY: 2012 ( Subtotal = $0 )
2012	2011	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	8/1/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $329,962 )
2011	2011	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	24	7/25/2011	NON-COMPETING CONTINUATION	$320,062
2011	2011	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	4/7/2011	SUPPLEMENT FOR EXPANSION	$9,900
														Subtotal = $329,962

Issue Date FY: 2010 ( Subtotal = $377,937 )
2010	2010	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	7/22/2010	NON-COMPETING CONTINUATION	$377,937
														Subtotal = $377,937

Issue Date FY: 2009 ( Subtotal = $402,438 )
2009	2009	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	2/19/2009	SUPPLEMENT FOR EXPANSION	$22,116
2009	2009	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	22	9/4/2009	NON-COMPETING CONTINUATION	$0
2009	2009	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	21	2/20/2009	SUPPLEMENT FOR EXPANSION	$0
2009	2009	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	22	7/22/2009	NON-COMPETING CONTINUATION	$380,322
														Subtotal = $402,438

Issue Date FY: 2008 ( Subtotal = $326,594 )
2008	2008	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	7/14/2008	NON-COMPETING CONTINUATION	$326,594
														Subtotal = $326,594

Issue Date FY: 2007 ( Subtotal = $326,594 )
2007	2007	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	7/19/2007	COMPETING CONTINUATION	$326,594
														Subtotal = $326,594

Issue Date FY: 2006 ( Subtotal = $350,198 )
2006	2006	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	8/4/2006	NON-COMPETING CONTINUATION	$350,198
														Subtotal = $350,198

Issue Date FY: 2005 ( Subtotal = $358,625 )
2005	2005	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	7/28/2005	NON-COMPETING CONTINUATION	$358,625
														Subtotal = $358,625

Issue Date FY: 2004 ( Subtotal = $358,625 ) (Continued on the next page)
Grand Total All Awards = $7,858,198

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Microtubule Dynamics and Axon Growth

Award Number: R01NS028785

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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