Genetic defects in the repair of DNA single-strand breaks result in human hereditary diseases that span a spectrum of neuropathology from progressive neurodegeneration in the mildest diseases to neurodevelopmental defects and seizures in the most severe. Recently, we identified a novel molecular mechanism that underpins such diseases, in which ‘programmed’ DNA breakage in gene enhancers and/or hyperactivity of the SSB sensor protein PARP1 disrupts the expression of genes critical for normal neural function. This project will extend and exploit these and other exciting recent discoveries using a combination of molecular, cellular, and neurophysiological techniques that include CRISPR-Cas9 gene editing in human cells, iPSC-derived human neurons, and ex vivo/in vivo mouse models of DNA break-induced synaptic dysfunction.
How to apply:
Please submit a formal application using the online system at www.sussex.ac.uk/study/phd/apply attaching a CV, degree transcripts and certificates, statement of interest and two academic references.
On the application system select Programme of Study – Genome Stability PhD. Please ensure you state the project title under funding and include the proposed supervisor’s name where required.
For enquiries about the project, contact supervisor: [Email Address Removed]