I am a first year PhD student working at the Institute of Genetic Medicine. My supervisors are Dr Patrick Yu-Wai-Man and Professor Patrick Chinnery. I am supported in my PhD by Dr Florence Burte and other members of the Newcastle Mitochondrial Research Group (MRG).
My PhD project has two main elements: (i) the identification of novel disease genes causing inherited optic neuropathies, and (ii) clarifying the disease mechanisms contributing to visual loss in patients with Wolfram syndrome secondary to pathogenic WFS1 mutations. My project will provide a greater understanding of the synergistic interactions between the ER and mitochondria, and how dysfunction in both compartments can result in disease states.
Disturbed interactions between mitochondria and the endoplasmic reticulum: implications for human disease
Inherited optic neuropathies cause significant visual impairment and affect at least 1 in 10,000 people in the United Kingdom. The pathological hallmark of inherited optic neuropathies is the preferential loss of retinal ganglion cells (RGCs) within the inner retina, which leads to optic nerve degeneration and subsequent visual failure.
Wolfram syndrome is an important cause of progressive irreversible visual loss. It is characterised by diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Most patients (~90%) harbour pathogenic mutations within the WFS1 gene. WFS1 encodes Wolframin, an endoplasmic reticulum (ER) transmembrane protein that is thought to regulate ER stress, the unfolded protein response (UPR) and calcium flux between the ER and mitochondria. The ER and mitochondria interact at interfaces termed mitochondria-associated-membranes (MAMS), which influence a broad range of functions, including, the unfolded protein response and programmed cell death.
This project aims to identify the causative genes in a well-characterised cohort of patients with inherited neuropathies and to investigate the disease mechanisms in Wolfram Syndrome.
Sponsor/funder: Institute of Genetic Medicine