Ataxia-Telangiectasia (A-T) is caused by mutations in the ATM kinase, a protein involved in DNA break repair, oxidative stress regulation and metabolism. We have generated iPSC from human patients with A-T to study the degeneration of the hindbrain in this disease. We use CRISPR-Cas9 genome editing tools to correct and introduce mutations in ATM in IPSC. From these cell lines we generate brain and liver organoids to understand pathogenesis in A-T, and to study the impacts of unrepaired DNA double strand breaks in ageing. We use multi-omics, advanced imaging technologies, scRNAseq and multi-electode arrays to probe the underlying molecular processes and to measure the impacts of therapeutics and gene therapy approaches.
Uutomated quantification of mitochondria in A-T neurons. Photo: Dr Hannah Leeson
