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Ultrastructural development and regeneration of nodes of Ranvier

Award Number: F32EY039079
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/18/2027
PERIOD OF PERFORMANCE END DATE: 02/17/2028

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Ultrastructural development and regeneration of nodes of Ranvier - PROJECT SUMMARY/ABSTRACT Rapid sensory processing in higher vertebrates is achieved through a form of neuronal signaling known as saltatory conduction. Saltatory conduction relies on specialized segments (nodes of Ranvier) of densely clustered ion channels that are spaced apart by insulating myelin sheaths. Proper tethering of ion channels within the node is critical for proper neural communication, and mutations in node scaffolding proteins cause developmental signaling disorders in humans. This project will investigate the molecular architecture (ultrastructure) of the node of Ranvier as it develops in the mouse optic nerve and regenerates after demyelinating injury. To understand how nodal protein complexes are established and organized in space, node proteins will be visualized in situ with cryo-electron tomography (cryo-ET). Aim 1 seeks to advance methods in cryo-ET by applying the laser phase plate—a microscope component that increases the contrast of electron imaging and allows for the collection of high-resolution images—to in situ tissue imaging of the node. This technique is expected to resolve the in situ conformations and binding interactions of small node proteins and serve as a benchmark for resolution obtained by in situ cryo-ET. Aim 2 seeks to characterize how the molecular architecture of the node is established during early postnatal development of the mouse optic nerve. This aim will use a combination of LPP-cryo-ET and conventional cryo-ET with immunogold labeling to elucidate how protein clustering at the node is initiated, how ion channel types are spatially organized by their protein tethers, how the unique cytoskeleton of the node is formed, and how node-myelin boundaries are maintained. Aim 3 seeks to characterize how node organization is lost and regenerated after demyelinating injury of the optic nerve. This aim will specifically compare degenerative and regenerative timecourses of nodes in young and old mice to further knowledge of how regenerative potential in the visual system is lost with age. Long-term impact to human vision research: Results from Aim 2 will elucidate the basic biology of node formation in the vertebrate optic nerve, furthering our mechanistic understanding of how the eye communicates with the brain. Aim 3 will set the foundation for studying ultrastructural and age-dependent node regeneration during demyelinating diseases that effect vision loss, including multiple sclerosis and neuromyelitis optica. The development of LPP-cryo-ET in Aim 1 will be broadly useful for the study of tissue ultrastructures, including the investigation of altered protein organizations arising from diseases and genetic disorders.


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 = $76,780 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	119 CALIFORNIA HALL	BERKELEY	CA	94720	ALAMEDA	USA	Vision Research	000	1	6/22/2026	NEW	$76,780
														Subtotal = $76,780

Grand Total All Awards = $76,780

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Ultrastructural development and regeneration of nodes of Ranvier

Award Number: F32EY039079

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/18/2027

PERIOD OF PERFORMANCE END DATE: 02/17/2028

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