UNVEILING THE ROLE OF SUMOYLATION AS NOVEL MOLECULAR PATHWAY IN MYELIN BIOLOGY; IMPLICATION IN NEURODEVELOPMENT AND DEMYELINATING PATHOPHYSIOLOGY.

Project Information

SUMOMyePath

Grant agreement ID: 101106517

DOI

10.3030/101106517

Project closed

EC signature date 13 July 2023

Start date 1 April 2024

End date 31 March 2026

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 188 590,08

Coordinated by

UNIVERSITA DEGLI STUDI DI TORINO
Italy

Periodic Reporting for period 1 - SUMOMyePath (UNVEILING THE ROLE OF SUMOYLATION AS NOVEL MOLECULAR PATHWAY IN MYELIN BIOLOGY; IMPLICATION IN NEURODEVELOPMENT AND DEMYELINATING PATHOPHYSIOLOGY.)

Reporting period: 2024-04-01 to 2026-03-31

Summary of the context and overall objectives of the project

Myelin is an essential biological structure that allows the nervous system to transmit information rapidly and efficiently. It is produced by specialised glial cells called oligodendrocytes in the central nervous system. When myelin is damaged, lost, or not properly maintained, neurological function can be severely affected. This is relevant to several neurodevelopmental, neurodegenerative and demyelinating conditions, including multiple sclerosis.

SUMOMyePath addressed an important knowledge gap in myelin biology: whether SUMOylation, a reversible molecular modification that regulates protein function, localisation and interactions, contributes to oligodendrocyte development, myelin formation and demyelinating pathology. While SUMOylation is known to regulate many cellular processes, its role in oligodendrocyte biology and myelin-related disease mechanisms remains insufficiently understood.

The overall objective of the project was to explore SUMOylation as a novel regulatory pathway in myelin biology, with the long-term aim of identifying new molecular mechanisms that may contribute to demyelinating disease and future remyelination-oriented strategies. The project combined molecular and cellular biology, glial-cell models, myelin biology and training in advanced neuroscience approaches. Its pathway to impact was based on generating mechanistic knowledge, developing experimental know-how and enabling resources, and strengthening future research capacity in the field of oligodendrocyte and myelin biology.

In the wider European context, the project contributes to the need for better understanding of chronic neurological diseases, improved research capacity in neurobiology, and training of highly skilled researchers able to work across molecular neuroscience, disease modelling, open science, communication and responsible research practice.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the project, work was performed to establish and develop experimental routes for studying the possible relationship between SUMOylation and oligodendrocyte biology. Activities included the preparation of cell-based approaches, optimisation of experimental workflows, development of molecular strategies, literature-based integration of SUMOylation and myelin biology, and the design of tools to support future knock-down, rescue and SUMOylation studies in glial-cell models.

A major part of the work focused on building enabling capacity for future mechanistic studies. This included the design of molecular tools and cloning strategies related to oligodendrocyte differentiation pathways, the development of experimental planning for SUMOylation-related studies, and the exploration of oligodendroglial cell models. The project also contributed to the critical evaluation of available in vitro models for oligodendrocyte differentiation and their suitability for future SUMOMyePath-related workflows.

The project included a research secondment that strengthened expertise in oligodendrocyte precursor cell biology, in vitro culture systems, calcium physiology and collaborative approaches to myelin research. This secondment supported scientific exchange, methodological training and the development of future collaborative perspectives.

The action also generated training and academic outputs. These included advanced teaching and training activities in neural-cell models, mentoring and researcher-development activities, and supervised thesis work linked to oligodendrocyte models and SUMOMyePath-relevant scientific questions. Dissemination activities included scientific presentations, internal research seminars, conference participation and planned scientific publications. Communication activities included public engagement events designed to explain brain biology, SUMOylation and myelin-related research to non-specialist audiences.

Overall, the project produced a set of enabling outcomes: strengthened expertise in myelin and oligodendrocyte biology, molecular-tool design for future mechanistic work, implementation know-how for glial-cell experimental systems, training outputs, public communication activities and follow-up dissemination and exploitation pathways.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

SUMOMyePath advanced a research direction that is still emerging: the connection between SUMOylation and oligodendrocyte or myelin biology. The project did not aim to deliver an immediate therapy or mature technology. Instead, it addressed an upstream biological question with potential long-term relevance for understanding demyelinating disease mechanisms.

The main progress beyond the state of the art lies in the integration of SUMOylation biology with oligodendrocyte differentiation, myelin biology and disease-oriented research. The project helped define experimental routes, molecular strategies and model-system considerations needed to investigate this connection more rigorously in future work. This includes the design of molecular tools for future knock-down and rescue approaches, the critical assessment of oligodendroglial in vitro models, and the development of know-how relevant to future studies of myelin-related cellular pathways.

The potential impact is primarily scientific and capacity-building at this stage. The project contributes to the foundations required for future research into molecular mechanisms controlling oligodendrocyte maturation and myelin maintenance. In the longer term, such knowledge could support the identification of new pathways relevant to remyelination, multiple sclerosis and other myelin-related disorders.

Further uptake will require additional validation of the molecular tools, further optimisation of experimental models, access to robust primary and disease-relevant systems, continued collaboration with specialised laboratories, and future funding to connect mechanistic discoveries with disease models and translational screening approaches. Planned scientific outputs, thesis work and follow-up collaborative proposals are expected to continue developing the knowledge and resources generated during the action.