Research Scholarships 2019: Project 2

Developing new treatments for inherited blindness.  Dr Niamh O'Sullivan

Dominant optic atrophy (DOA) is a neuro-ophthalmic condition characterized by bilateral degeneration of the optic nerves, causing visual loss typically within the first decade of life. The disease primarily affects the retinal ganglion cells and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the brain. DOA affects over 20,000 people in Europe, yet there are currently no effective treatments and visual loss is irreversible (https://eyewiki.aao.org/Autosomal_Dominant_Optic_Atrophy).

Mutations in OPA1 are known to cause DOA. The protein encoded by OPA1 localises to the mitochondrial membrane where it functions to regulate mitochondrial dynamics (fusion and fission), respiratory chain function and mitochondrial quality control (mitophagy). However, the mechanism(s) by which mutations in these genes underpin retinal ganglion cell degeneration in DOA is not known (Del Dotto et al., 2018).

In this PhD project, you will work in both the O’Sullivan (https://fniamhy.wixsite.com/osullivanlab) and Kennedy (https://people.ucd.ie/brendan.kennedy) research groups at University College Dublin to generate and investigate novel Drosophila and zebrafish models of DOA with which you will be able to study neurodegeneration and identify therapeutic targets. You will also have the opportunity to undertake some of your research with an industry partner in Barcelona. In this project you will use CRISPR and RNAi technologies to modify OPA1 expression in vivo, confocal microscopic analysis to study mitochondria within neurons and perform a drug screen to identify compounds that rescue visual defects in your DOA models.  This work will:

a) Provide high impact insights into the fundamental role of mitochondrial organisation in neurons by generating synergistic findings in vertebrate and invertebrate models

b) Clarify how mutations in mitochondrial membrane proteins cause axonal degeneration

c) Develop novel targets for therapeutic approaches to neurodegeneration.

 

Enquiries and applications (to include cover letter and CV) to Dr Niamh O'Sullivan. Email: niamh.osullivan@ucd.ie

 

Closing date: Friday 31st May, 2019.