Discovering novel genes and pathways to ataxia

Summary Discovering novel genes and pathways to ataxia

Project Details

Ataxia is the term for a group of neurological diseases that affect movement and coordination, impacting ~1:15,000 individuals. While there is considerable evidence that gene mutations cause ataxia, currently only ~30% of affected individuals receive a genetic diagnosis. A focus of our research is to identify novel genes that cause ataxia.

We have recently identified a novel genetic cause of ataxia, caused by a pathogenic repeat expansion. This is when a segment of repetitive DNA, termed a short tandem repeat, is significantly expanded in size compared to the general population. This project will utilise modern genomic technologies, including exome and genome sequencing and transcriptomics to characterise the size and structure of this novel repeat expansion. Subsequently, the expansion will be characterised in model systems, including patient-derived induced pluripotent stem cells (iPSC), to generate brain cell cultures to study disease-specific mechanisms and test potential drug treatments. The research will develop both 2D and 3D organoid models, with a focus on neurons of the cerebellum as these appear to be selectively lost during development of ataxia. The successful candidate will get the opportunity to learn a range of laboratory techniques including stem cell culturing, differentiation of stem cells into neurons, electrophysiology, immunocytochemistry, microscopy, drug screening assays, real-time qPCR and western blot analysis. In addition they will work closely with clinicians and bioinformaticians within a large multidisciplinary team.