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Using cryo-electron tomography and live-cell fluorescent imaging to study the role of cofilin in regulating neuronal filopodial structure and dynamics

Award Number: R01NS126448
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Using cryo-electron tomography and live-cell fluorescent imaging to study the role of cofilin in regulating neuronal filopodial structure and dynamics - Project Summary/Abstract How neurons guide their processes to the correct binding partner is a complicated task, but is critical during development and recovery from injury. It involves the highly coordinated action of many cytoskeletal proteins and their binding partners within the growth cone at the tips of extending neurites, as they feel their way through the neuropil. There is a lot known about the signaling pathways that regulate neurite outgrowth and turning, but the details of how molecular structures come together to achieve growth cone behavior are still unclear. This project will initially focus on the structure of bundled cofilactin filaments (cofilin-decorated F-actin) in situ, and how this novel filament structure and fascin cross-linking determine filopodial dynamics. Here we propose that filopodial behavior is governed partially by the transition from the fascin cross-linked to a cofilin cross-linked filaments, that makes filopodial bundles more pliable. Experiments are focused around three aims: 1) to study the high-resolution structure of fascin- and cofilin-linked actin bundles to determine their impact on actin structure, 2) to determine how changes in fascin and cofilin concentration regulate filopodial dynamics and structure, and 3) determine how LIMKI and SSH1 form the core of a bidirectional regulatory mechanism for regulating actin architecture via tuning the phosphorylation state of Ser3 on cofilin.


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 = $357,869 )
2025	2025	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/17/2025	NON-COMPETING CONTINUATION	$357,869
														Subtotal = $357,869

Issue Date FY: 2024 ( Subtotal = $397,822 )
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/24/2024	NON-COMPETING CONTINUATION	$28,709
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/16/2024	NON-COMPETING CONTINUATION	$369,113
														Subtotal = $397,822

Issue Date FY: 2023 ( Subtotal = $435,446 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/10/2023	NEW	$435,446
														Subtotal = $435,446

Grand Total All Awards = $1,191,137

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Using cryo-electron tomography and live-cell fluorescent imaging to study the role of cofilin in regulating neuronal filopodial structure and dynamics

Award Number: R01NS126448

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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