Analysis of RNAseH2a function in Neurodegeneration

Poor DNA repair and genome instability are not only involved in cancer, but also implicated in neurodegenerative diseases. For instance, repeat expansions in the C9ORF27 gene are major cause of motoneuron disease. These expansions were recently shown by the El-Khamisy group to inhibit ATM, a gene that is central to detection and repair of DNA. The ATM gene causes neurodegeneration itself. DNA damage may also be at the basis of age-related neural cell loss. In vivo models are essential to understand diseases like neurodegeneration because they result from highly complex cell- and tissue interactions. We are using the zebrafish embryo as an optically and genetically accessible model to do this, and to screen for neuroprotective drugs (see figure). For this project, we have created models for RNAse deficiencies in fish. This will lead to DNA damage by deficient repair of misincorporated ribonucleotides into the DNA backbone. These animals are a model of Aicardi-Goutières syndrome (AGS), a disease associated with an inflammatory phenotype, a progressive neurological phenotype and microcephaly. We will use this model to study its precise function and to perform in vivo drug screens in embryos to identify drug that might suppress the gene defect, as a first step towards a drug for patients.

Entry Requirements
Candidates must have a first or upper second class honors degree or significant research experience. (add any additional requirements here)

Enquiries
Dr Fredericus van Eeden, [Email Address Removed], tel 0114 2222348

How to apply
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select (BMS) as the department.