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Sculpting Membrane Dynamics: Membrane-Remodeling Factors Shape Oligodendroglial Form and Function

Award Number: R01NS140424
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: 03/01/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2029

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Sculpting Membrane Dynamics: Membrane-Remodeling Factors Shape Oligodendroglial Form and Function - Project Summary Oligodendrocytes in the central nervous system wrap multilamellar compact myelin membranes around axons and dramatically facilitate action potential propagation. Compromised myelination results in neurological deficits in myelin diseases and nervous system injuries. However, myelin sheaths don't look the same. There is vast morphological heterogeneity, and the morphological parameters of myelin sheaths play a key role in determining axon conduction velocity and circuit functions and influencing behavior. Development, plasticity and repair of neural circuits require proper (re)establishment of myelin profiles, which undoubtedly involves extensive membrane remodeling to shape oligodendroglial form and function. Nevertheless, how membrane remodeling is regulated during myelination is still poorly understood. In this proposed research, we focus on a family of intracellular membrane-remodeling factors which can bind to and bend plasma membranes and contain functional domains interacting with actin or actin regulators. They may thus act at the very forefront of membrane morphological changes and represent a major, paradigm-shifting mechanism for oligodendroglial membrane remodeling. Therefore, we propose that this group of membrane-binding factors regulate oligodendroglial membrane remodeling and play a pivotal role in CNS myelination through (a) cell process elaboration, (b) initial membrane enlargement, or (c) radial and (d) longitudinal membrane expansion, which in turn could regulate the number of myelin sheaths per oligodendrocyte, sheath length, or myelin thickness and determine the extent of myelination and myelin profiles. In this proposed research, we will (1) conduct expression profiling to identify the factors in this protein family that are expressed in oligodendroglia and perform gain-of-function analysis to determine their sufficiency to remodel the morphology of oligodendroglia and myelin sheaths, (2) perform loss- of-function analysis to determine their necessity to establish proper morphological complexity of oligodendroglia and shape CNS myelination, and (3) determine their necessity to promote proper remyelination kinetics using a focal demyelination mouse model. Accomplishing the proposed aims will unravel the roles of these intrinsic membrane-remodeling factors in oligodendroglia and CNS (re)myelination and may provide key insights into how these molecules are regulated through neuron-glia interactions to shape the myelin landscape and fit the need for proper neural circuit functions in the future.


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 = $458,189 )
2026	2026	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/26/2026	NON-COMPETING CONTINUATION	$412,371
2026	2026	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/18/2026	NON-COMPETING CONTINUATION	$45,818
														Subtotal = $458,189

Issue Date FY: 2025 ( Subtotal = $458,189 )
2025	2025	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/28/2025	NEW	$458,189
														Subtotal = $458,189

Grand Total All Awards = $916,378

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Sculpting Membrane Dynamics: Membrane-Remodeling Factors Shape Oligodendroglial Form and Function

Award Number: R01NS140424

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: 03/01/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2029

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