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POS-ERC-Støtte til ERC søkere som oppnår god evaluering

Role of novel DNA double strand break repair factors in immune system development

Tildelt: kr 0,50 mill.

Cells have sensitive mechanisms for detecting and repairing deleterious breaks in DNA, and defects in DNA repair pathways result in complex disorders, including immunodeficiency, neurodegeneration and various cancers. During early lymphocyte development however, double strand breaks are created on purpose to enable V(D)J recombination. This process is thought to rely on a set of Non-Homologous End-Joining DNA repair factors, which are required for the maturation of B and T lymphocytes. However, the presence of DNA breaks also activates many DNA damage response (DDR) factors, including chromatin-modifying enzymes. Many of these factors have overlapping functions and their role in lymphocyte development has not been investigated because of a lack of appropriate models. To overcome the current challenge of functional redundancy between these factors, I propose a multidisciplinary and innovative project involving genetic models with the combined inactivation of several genes, to study the role of DDR factors in early B cell development. To strengthen my following ERC grant application, I aim to generate a number of cell lines with genetically inactivated DDR factors. We will use these cells to determine the role of DDR factors in V(D)J recombination. With these data I will have convincing preliminary results for this high gain project.

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POS-ERC-Støtte til ERC søkere som oppnår god evaluering

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