I am a PhD student working under the supervision of Dr. Yu-Wai-Man and Professor Patrick Chinnery in the Welcome Trust Centre for Mitochondrial Research. My primary research interest lies in the mitochondrial mechanisms that underpin neuronal loss in neurodegenerative disorders. Mitochondria are central to a diverse range of cellular processes and they are dynamic organelles, undergoing constant fission and fusion as part of an extended mitochondrial network. This highly interconnected network has the ability to adapt to extracellular stress by altering its morphology and a number of key regulators of mitochondrial dynamics been identified. It is therefore not surprising that an increasing number of human diseases are being linked with pathological imbalances of mitochondrial fusion and fission. The mechanistic pathways involved in these disease states are complex and they still remain to be clarified.
I have a background in human genetics, biochemistry and cell biology. My objective is to use DOA, secondary to OPA1mutations, as a tractable model system to investigate how disturbed mitochondrial fission and fusion lead to human disease.
Investigation of disease mechanisms which contribute to multi-system tissue involvement in dominant optic atrophy due to OPA1 mutations.
Principal Investigators: Dr Patrick Yu-Wai-Man and Professor Patrick Chinnery
Other staff members involved: Dr. Florence Burte
Autosomal Dominant Optic Atrophy (DOA) is the most common inherited form of mitochondrial blindness in the general population and the majority of patients harbor pathogenic mutations in the OPA1 gene. DOA can present in two clinical forms; with isolated optic nerve involvement (pure DOA) or in association with additional neurological features (DOA+). The fundamental question underlying my research is why a subgroup of patients develops DOA+ features, resulting in increased neurological disability in addition to a worse visual prognosis.
During my PhD project, I will dissect the key molecular mechanisms that precipitate neuronal loss in DOA and the development of the more severe DOA+ phenotypes. Our ultimate aim is to develop effective treatment strategies aimed initially at rescuing retinal ganglion cells to prevent progressive visual deterioration in affected OPA1 mutation carriers. A better understanding of these fundamental mechanisms that underlie DOA will also have broader implications for other neurodegenerative disorders where neuronal loss has been linked with disturbed mitochondrial dynamics and defective mitochondrial biogenesis.
Sponsor/Funder: Medical Research Council UK