Project description
Genetic insight into multiple sclerosis
Multiple sclerosis (MS) is an autoimmune disease that targets the myelin insulating sheath of axons in the central nervous system. Genome-wide studies have identified various genetic variants associated with MS risk, primarily linked to immune cell genes. Funded by the European Research Council, the SingleMS project will use single-cell omics to investigate the active role of oligodendrocytes, the myelin-producing cells. The focus will be on the chromatin accessibility and gene expression of these genetic variants related to these single-nucleotide polymorphisms/variants. Characterisation of the transcriptomic and epigenomic landscape in human oligodendrocytes will provide important insight into MS pathogenesis, paving the way for potential therapeutic strategies.
Objective
Multiple sclerosis (MS) is a neurological disease characterized by autoimmune attack targeting oligodendroglia (OLG) in the central nervous system (CNS), and in particular their myelin, which ensheaths neuronal axons. Genome-wide association studies (GWAS) have led to the identification of hundreds of single-nucleotide polymorphisms (SNPs) and variants that are associated with MS risk. Many of these are located near genes associated with immune cells, indicating a key role for these cells in MS. Using single-cell omics approaches, we recently found that OLG present chromatin accessibility or express genes associated with some of these SNPs/variants, both in health and disease. Here, we hypothesize that OLG have a more active role in MS than previously anticipated, and therefore we will determine the function of MS SNPs/variants in OLG in the context of MS, using humanized mouse models, patient samples and new single-cell omics techniques recently developed in my group. We will 1) characterize in-depth the transcriptomic and epigenomic landscape of human and mouse OLG in the context of MS, to identify putative genes affected by the SNPs/variants; 2) perform CRISPR-guided editing of a cohort of the identified SNPs/variants in human OLG, and determine the consequences of the editing at a) an epigenomic and transcriptional level, linking specific SNPs/variants to their bona-fide target genes, and b) a functional level, by performing an array of functional assays targeting myelination, cell survival, and immune function, both in vitro and in humanized mouse chimeras in which engineered human OLG have been transplanted. We will use single-cell and spatial omics technologies, such as nanoCUT&Tag and spatial CUT&Tag, among others which we have recently developed in my research group. The results of this project will yield unique insights into the role of OLG and the identified SNPs/variants in MS, and thereby pave the way to novel therapeutic avenues for this disease.
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.
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.
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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.1.1 - European Research Council (ERC)
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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.
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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-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-ADG
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171 77 STOCKHOLM
Sweden
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