Objective
Plasma cells (PCs) are antibody-producing cells that develop from activated B cells in an immune response. Antibodies produced by these cells are essential for the clearance of pathogens and long-term protection against recurrent infections. PCs can also be pathogenic in autoimmune disease, where self-recognising antibodies are produced, and cancer, in the form of multiple myeloma. An understanding of the molecular pathways that control PC function is therefore necessary for understanding human immunity and these pathologies. Interferon Regulatory Factor 4 (IRF4, gene name Irf4) is a transcription factor whose deletion in mouse models results in the loss of all PCs. Because of this, the genes that are regulated by IRF4, and hence which cellular pathways are required for PC survival, are unknown. Here, I propose to use a revolutionary approach to determine the target genes of IRF4. I will use targeted protein degradation to deplete IRF4 in mouse PCs, and then determine the immediate changes in transcription following IRF4 loss using a state-of-the-art RNA sequencing technique, known as SLAM-seq. The advantage of this approach is that I can analyze changes in transcription before the onset of the survival defect. I will then study the functional roles of the identified IRF4 target genes in PCs. This is a multidisciplinary project that combines molecular biology approaches with cell biology and immune physiology. In addition, this proposal allows for transfer of knowledge from myself, an expert in the regulation of cell survival, and the host institution, which will train me in molecular biology techniques and expertise in PC biology. IRF4 has been implicated in both autoimmune disease and multiple myeloma, and so this proposal addresses a basic research question that has translatable outcomes. Hence, this proposal is in line with the H2020 objective to increase the transfer of knowledge into tangible products, and contributes to the European knowledge-based economy.
                                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.
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology
- natural sciences biological sciences molecular biology
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            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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
                                      MAIN PROGRAMME
                                    
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                  H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
                                    
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            Topic(s)
            
              
              
                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.
                
              
            
          
                      
                  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.
MSCA-IF-EF-ST - Standard EF
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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) H2020-MSCA-IF-2018
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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.
1030 Wien
Austria
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