Investigating neurodegeneration in a zebrafish model of Ataxia Telangiectasia

Recessively inherited loss of function mutations in ATM cause Ataxia-Telangiectasia (A-T). ATM functions as a protein kinase that is activated by autophosphorylation in response to DNA double strand breaks, and in turn activates either DNA repair or apoptosis. The major clinical symptom in A-T patients is ataxia caused by cerebellar neurodegeneration, however the mechanisms by which loss of ATM leads to death of cerebellar neurons in vivo are unclear. One of the main reasons for the current lack of understanding is the failure to establish a tractable vertebrate model of A-T that develops cerebellar neurodegeneration.

An exciting opportunity has arisen to work on a zebrafish model of Ataxia Telangiectasia. The project will involve CRISPR/Cas9 mediated genome editing, characterisation of mutant zebrafish, and in vivo investigation of the underlying mechanisms of disease. You will also generate ATM mutant zebrafish with fluorescent Purkinje cells to enable in vivo drug screens for potentially therapeutic compounds.

You will be based in state of the art research facilities at the Sheffield Institute of Translational Research and the Bateson Centre, both located at the University of Sheffield.