Mitochondrial Dysfunction and Fuchs Endothelial Corneal Dystrophy

The corneal endothelium is a metabolically-active monolayer of non-dividing cells on the posterior surface of the cornea, which maintains corneal transparency and vision, by sodium-activated ATPase pumping of water. Fuchs endothelial corneal dystrophy (FECD) is the most common cause of corneal endothelial degeneration and is characterized by alterations in corneal endothelial cell morphology, progressive loss of cells, and the accumulation of extracellular deposits that eventually lead to corneal oedema, opacity and subsequent visual loss. FECD is a bilateral ageing disorder of the endothelium and most commonly occurs in patients in their 40s-50s and affects 5% of the population over 40 in the USA. The loss of corneal endothelial cells in FECD is permanent and corneal transplantation is the only treatment modality that can restore lost vision, making FECD a leading cause of corneal transplantation. Cataract surgery can accelerate progression of FECD and insight into the biological mechanisms of endothelium cell loss has direct relevance to all patients undergoing cataract surgery.

FECD is an ageing disorder of the endothelium which results from the interaction of genetic and environmental factors. There is a body of evidence that oxidative stress contributes to cellular injury in FECD. The corneal endothelium is prone to oxidative stress as it experiences a lifelong exposure to light, high oxygen demand and metabolic activity to continually pump ions using by Na+K+ATPases, and post-mitotic arrest. The corneal endothelium is packed with mitochondria to maintain the metabolic demands of its functional role of ATPase pumping of water. Any malfunction of the mitochondrial electron transport chain results in an excessive generation of free radicals and can result in oxidative stress, which is a critical factor in FECD. Mitochondria might be specific targets of oxidant-induced damage in susceptible corneal endothelial cells in FECD.

The student will be trained in a broad context in ocular biology, corneal endothelial biology, mitochondrial genetics and mitochondrial function/ROS signalling. This will include:
- research-specific skills: processing human tissue samples, cell culture, immunocytochemistry, DNA and RNA extraction, mtDNA sequencing and bioinformatics, measures of mitochondrial function (l (ΔΨm), measures of mitochondrial content (citrate synthase and mtDNA copy number with qPCR), measures of oxidative damage (intra-cellular and mitochondrial oxidative stress, aconitase activity, 8-OHdG levels), assessment of mitophagy using immuno-cytochemistry and Western blotting for PINK1 and Parkin, phenotypic rescue of mitochondrial function using MitoQ and CoQ10.
- generic research skills: critical thinking, IT skills, scientific integrity, ethics, project and time management, scientific writing, presentation skills and public engagement;
- transferable skills: personal effectiveness, oral and written communication skills, networking and teamwork, management and leadership, understanding of research context.

The Institute of Ageing and Chronic Disease is part of the Faculty of Health and Life Sciences. We excel in high quality research that contributes to improved health and quality of life for older people and animals and alleviates chronic diseases at all ages. Our departments are now seeking to attract highly motivated self-funded PhD candidates of outstanding ability to join our internationally rated research teams.

The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. We offer a supportive working environment with flexible family support for all our staff and students and applications for part-time study are encouraged. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

The successful candidate should have, or expect to have an Honours Degree at 2.1 or above (or equivalent). Candidates whose first language is not English should have an IELTS score of 6.5 or equivalent. This project is most suitable to a student with an undergraduate degree or Master’s degree in the Life Sciences (Biology, Genetics, Biochemistry, Biomedical Sciences, Cell Biology, and Medicine).

Informal enquiries regarding this project should be made to Prof Colin E Willoughby ([Email Address Removed]) or Dr Hannah Levis ([Email Address Removed]).

To apply send your CV and covering letter by email to Prof Colin E Willoughby ([Email Address Removed]) or Dr Hannah Levis ([Email Address Removed]) with a copy to [Email Address Removed]

All general enquiries should be directed to Mrs Sue Jones ([Email Address Removed]).