Spinocerebellar ataxia type 1 (SCA1) is a rare inherited neurological disorder that follows an autosomal dominant pattern. It is caused by an abnormal expansion of CAG repeats in the ATXN1 gene. When this gene is transcribed, the resulting messenger RNA carries the expanded CAG repeat. During translation, this abnormal sequence produces a mutant ataxin-1 protein. The mutant protein tends to misfold and form aggregates within neurons. Over time, these aggregates lead to progressive neurotoxicity and degeneration of affected brain regions.
In the Neuro-D group, we focus on studying disease pathology using patient-derived fibroblast cells and induced pluripotent stem cells (iPSCs). These iPSCs can be differentiated into neuronal cultures or developed into 3D brain organoids. In our lab, neuronal cultures are widely used to perform functional assays. We apply various techniques, including multi-electrode array (MEA) recordings, assays to test mitochondrial function, RNA sequencing and high-throughput imaging. Together, these approaches allow us to uncover disease-specific mechanisms and gain deeper insights into SCA1. The brain organoids allow us to model complex brain architecture and disease mechanisms. Both systems provide valuable insights into cellular and molecular changes underlying neurological disorders. In addition, we use these models as platforms to test and evaluate potential therapeutic interventions.
More info on the disease and our projects can be found on the SCA1 website.