R-loops are non-canonical RNA/DNA structures, formed in all living organisms where they play crucial roles in regulating gene expression, DNA and histone modifications, generation of antibody diversity, DNA replication and genome stability. The work from the lab have demonstrated that R-loops are also implicated in human diseases, including neurodegeneration and cancer. However, the molecular mechanisms associated with R-loop functions in health and disease are not fully understood.
The main aim of this project is to understand the regulation of R-loops in human cells and uncover the molecular mechanisms which lead to R-loop-associated diseases. We will employ state-of-the-art techniques including CRISPR, Mass Spectrometry, next-generation sequencing, and molecular biology approaches to understand the principles of R-loop biology in health and disease. The results generated in this project will help to understand the pathology of trinucleotide expansion disorders, including Fragile X syndrome and Friedreich ataxia, associated with pathological R-loops. The findings from this project will pave the way for the development of new therapeutic approaches for these disorders.
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