Myelin Membrane in Molecular Detail

Projektinformationen

MyeMembrane

ID Finanzhilfevereinbarung: 101151099

DOI

10.3030/101151099

Das Projekt endete am 31 Mai 2026

EK-Unterschriftsdatum 6 März 2024

Startdatum 1 April 2024

Enddatum 31 Dezember 2026

Finanziert unter

• Marie Skłodowska-Curie Actions (MSCA)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 210 911,04

Koordiniert durch

UNIVERSITETET I BERGEN
Norway

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

Berichtszeitraum: 2024-04-01 bis 2026-12-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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.