Title:
Investigating novel therapeutic strategies for severe neurodegenerative disease
Description:
Hereditary spastic paraplegias (HSPs) are a group of progressive neurodegenerative conditions characterized by progressive degeneration of the longest upper motor neurons. While mutations in the endoplasmic reticulum-shaping protein Atlastin-1 are a leading cause of HSP, our clinical collaborators have recently found that certain mutations in this gene cause an extremely severe form of disease involving widespread neuronal disruption (Alecu et al., 2023; PMID: 35925862). It is unlikely that existing disease models and therapeutic strategies, currently under development for classic forms of HSP, will be suitable for children with mutations causing severe disease.
The O’Sullivan research group at University College Dublin are now offering 2 fully funded PhD projects to develop novel models and identify potential therapeutic targets to lessen neurodegeneration in severe HSP caused by mutations in the Atlastin gene.
PhD project 1: Using human cellular models of disease, you will design and screen oligonucleotides targeting severe disease-causing forms of Atlastin-1, optimise safety of targeted oligos and assess their efficacy of reducing degeneration in patient-derived induced pluripotent stem cells.
PhD project 2: In this project you will work with in vitro and in vivo Drosophila (fruit fly) models of disease. You will use CRISPR gene editing to generate fly models of severe HSP, screen potential knockdown oligos for target specificity and examine how these knockdown oligos alter neurodegenerative phenotypes in your fly model of disease.
The findings from this work will provide insights into the mechanisms by which mutations in Atlastin give rise to severe disease and will seek to identify a novel therapeutic strategy for the treatment of this disease.
· Start date: September 2024
· Full EU fees + €22,000 per annum stipend over four years
· Candidate will have a BSc or MSc in genetics, cell biology, biochemistry or a related discipline
Enquiries and applications (to include cover letter and CV) to Associate Professor Niamh O’Sullivan. Email: niamh.osullivan@ucd.ie.
Applications open immediately but no later than Friday 31st May 2024
Posted on 29/04/2024
