Understanding the Pathogenesis of Friedreich’s Ataxia by Single-Cell Integration of Gene Expression, Epigenetics and Connectivity in the Cerebellar Nuclei

One of the key features of FA is the selective loss of specific neurons in the cerebellum, particularly in the dentate nucleus (DN), which is involved in motor coordination. However, the specific cell type affected by the disease and the reasons for this selective neuronal loss are still unclear. Additionally, changes in brain connectivity that occur before cell death are not well understood. To address these questions, this research project aims to identify the specific cell type within cerebellar nuclei affected in FA and understand its role in disease progression. The project will use cutting-edge technologies to study the brain at a single-cell level in an FA mouse model to gain new insights into the disease mechanisms, including changes in brain connectivity that precede cellular loss. This approach will enable the study of the pathogenesis at different time points rather than solely at the end stage typically observed with human tissue. Understanding how and what specific cell types are affected by the disease and the changes in brain connectivity may lead to new therapeutic strategies that could slow or prevent the progression of the disease.