Project description
Epigenetic therapies for multiple sclerosis
Multiple sclerosis (MS) is a progressive immune-associated disorder of unknown cause. The EU-funded Epi4MS project is working under the hypothesis that MS is triggered by epigenetic changes which affect gene expression but not the genetic code. Researchers will identify and link epigenetic states with MS pathogenesis and test the therapeutic potential of targeted epigenome editing in mouse models of the disease. Results will help determine the underlying molecular mechanisms of MS and pave the way for innovative treatments. Moreover, they will lay the foundation for reversing aberrant epigenetic states in other aggressive immune-related diseases.
Objective
Multiple Sclerosis (MS) is a leading cause of unpredictable and incurable progressive disability in young adults. Although the exact cause remains unknown, this immune-mediated disease is likely triggered by environmental factors in genetically predisposed individuals. I propose that epigenetic mechanisms, which regulate gene expression without affecting the genetic code, mediate the processes that cause MS and that aberrant epigenetic states can be corrected, spearheading the development of alternative therapies. We will exploit the stable and reversible nature of epigenetic marks, in particular DNA methylation, to gain insights into the novel modifiable disease mechanisms by studying the target organ in a way that has not been possible before. This highly ambitious project comprises three synergistic facets formulated in specific aims to: (i) identify epigenetic states that characterize the pathogenesis of MS, (ii) prioritize functional epigenetic states using high-throughput epigenome-screens, and (iii) develop novel approaches for precision medicine based on correcting causal epigenetic states. Our unique MS biobank combined with cutting-edge methodologies to capture pathogenic cells and measure their functional states provides a rational starting point to identify MS targets. I will complement this approach with studies of the functional impact of MS targets using innovative in vitro screens, with the added value of unbiased discovery of robust regulators of specific MS pathways. Finally, my laboratory has extensive experience with animal models of MS and I will utilize these powerful systems to dissect molecular mechanisms of MS targets and test the therapeutic potential of targeted epigenome editing in vivo. Our findings will set the stage for a paradigm-shift in studying and treating chronic inflammatory diseases based on preventing and modulating aggressive immune responses by inducing self-sustained reversal of aberrant epigenetic states.
                                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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                  H2020-EU.1.1. - EXCELLENT SCIENCE - 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.
ERC-COG - Consolidator Grant
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              Call for proposal
                
                  
                  
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(opens in new window) ERC-2018-COG
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171 77 STOCKHOLM
Sweden
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