We investigate various aspects of genome dynamics that integrate ADP-ribose metabolism and RNA biology in the context of genome maintenance and expression in normal and pathological situations, including cancer and neurological diseases, especially neurodegeneration. We explore the molecular mechanisms by which DNA strand breaks are detected and repaired and we are particularly interested in identification and characterization of protein factors and pathways that link aberrant ADP-ribose and/or RNA metabolism to neurodegenerative disease. We aim to examine whether the deregulated ADP-ribose metabolism at sites of DNA breaks extends beyond rare DNA repair-defective diseases to dementia, a neurodegenerative disease that presents the greatest threat to normal ageing and health. The cause of neurodegenerative disorders is often genetic; however, the involved genes and the underlying mechanisms are increasingly diverse, indicating the complexity of brain development and growth. Additionally, since several infections have been associated with the risk of cognitive impairment and neurodegeneration, we investigate the effect of bacteria- and virus-derived stimuli on the disease onset and progression. Ultimately, we envisage that our work will lead to new therapeutic avenues for the clinical treatment of neurodegenerative disease.
