Myelin Membrane in Molecular Detail

Información del proyecto

MyeMembrane

Identificador del acuerdo de subvención: 101151099

DOI

10.3030/101151099

Proyecto finalizado el 31 Mayo 2026

Fecha de la firma de la CE 6 Marzo 2024

Fecha de inicio 1 Abril 2024

Fecha de finalización 31 Diciembre 2026

Financiado con arreglo a

• Marie Skłodowska-Curie Actions (MSCA)

Coste total

Sin datos

Aportación de la UE

€ 210 911,04

Coordinado por

UNIVERSITETET I BERGEN
Norway

Periodic Reporting for period 1 - MyeMembrane (Myelin Membrane in Molecular Detail)

Período documentado: 2024-04-01 hasta 2026-12-31

Resumen del contexto y de los objetivos generales del proyecto

Myelin plays a critical role in rapid action potential propagation and neuronal metabolism support. Disruptions in its formation lead to severe neurodegenerative conditions, with multiple sclerosis (MS) ranking as the most prevalent demyelinating disorder in the central nervous system (CNS). The Multiple Sclerosis International Federation estimates that around 2.9 million individuals worldwide are affected by MS in 2023, and its prevalence is increasing yearly. It is well established that myelin-specific membrane-embedded and membrane-associated proteins are essential for wrapping the oligodendrocyte membrane around the axons, forming the tightly packed membrane multilayers, constituting the myelin sheath. While the molecular identity of these proteins is known, there is no high-resolution structural information for any of the CNS myelin proteins, and equally, how these proteins interact among themselves and with the surrounding membrane to form the myelin sheath is unknown. MyeMembrane seeks to throw structural insight onto myelin sheath assembly by visualizing principal CNS myelin membrane proteins in lipid environment at high resolution, and to investigate the interplay between myelin proteins and the surrounding membrane using cutting-edge biophysical techniques. Unravelling the structural basis of myelin sheath formation is crucial for understanding the underlying disorders, and for exploring new research avenues including the development of new treatments, endowing MyeMembrane with far-reaching scientific and societal impact.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

To solve the structures of myelin proteins (the work carried out mostly concerned MAL and PLP), V. Kalienkova has focused on 1) developing fiducials to increase the size of target proteins and enable single particle cryo-EM for small myelin proteins and 2) optimising cryo-EM data collection and processing specifically for small proteins. V. Kalienkova has established reconstitution protocols for both proteins into SapA lipid particles. Further, V. Kalienkova focused on exploring nbALFA and ALFA-tag as a fiducial for cryo-EM, and additional modifications of nbALFA, achieving a low resolution reconstruction of MAL (~10 Å) in SapA lipid particles.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

The project has been terminated early, and the expected results beyond state of the art (high-resolution structures of several myelin proteins) have not been achieved.