Project description
Understanding oligodendrocyte resilience in multiple sclerosis
Multiple sclerosis is a chronic demyelinating disease, in which the brain progressively loses its ability to repair damaged myelin. While current therapies target inflammation, strategies that promote long-term remyelination remain limited. With the support of the Marie Skłodowska-Curie Actions programme, the ResilMS project aims to investigate why some oligodendrocytes remain resilient and capable of remyelination during prolonged disease. Using lineage tracing combined with single cell and spatial transcriptomics in a chronic mouse model, the project will determine the molecular profile of existing and newly generated oligodendrocytes. The goal is to identify resilience pathways and genetic players, which could be utilised for future diagnostic and therapeutic strategies for multiple sclerosis.
Objective
Multiple sclerosis (MS) is a prevalent demyelinating disease that primarily affects young adults. Current therapy for MS mainly focuses on immune suppression and alleviating inflammation. However, efforts to promote remyelination face challenges in clinical translation. Animal models of acute demyelination have demonstrated promising remyelination, primarily facilitated by newly generated oligodendrocytes. Nevertheless, the scenario in human MS differs, as the disease typically manifests in adulthood and the progression of lesions occurs over several decades.
In the proposed project ResilMS, by using barcode based lineage tracing combined with ultra-depth single-cell and spatial transcriptomics, I will identify the molecular profiles of existing and newly generated oligodendrocytes at different stages of a mouse model induced with experimental autoimmune encephalomyelitis (EAE). The aim is to comprehend how an oligodendroglial cell pool diversifies its subpopulations during prolonged disease challenge, and what are the unique molecular properties for resilient cells to maintain their ability to endure an adverse inflammatory environment and remyelinate. Further, I will perform a screen of single nucleotide polymorphisms (SNPs) associated with risk and severity of MS that might affect genes related to the resilience of oligodendrocytes. To experimentally explore the effect of relevant SNPs, human oligodendrocyte cells (hOLGs) derived from pluripotent cells will be perturbed with CRISPR-based genetic modification and observed for cell profile and functional changes.
The identified SNPs and resilience molecular pathways may play a critical role in disease progression for MS patients. By delving into the mechanisms of resilience of (re)myelinating cells in a long disease course, this project will provide valuable insights into MS-related genetic risk and protective factors, and potentially advance diagnostic and therapeutic approaches in MS research.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
171 77 STOCKHOLM
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.