I am a first year PhD student working under the supervision of Dr. Bobby McFarland and Prof. Rob Taylor. I hold a BSC in Chemistry (University of York) and an MRes in Cancer (Newcastle University). After the completion of my MRes I spent a year in research in the faculty of dermatological sciences (Newcastle University). I was always extremely interested in understanding the role of mitochondria in the molecular basis of disease.
As a PhD student, I am now working on the role of POLG mutations in human disease, with a particular interest in a rare infantile disorder known as Alpers-Huttenlocher syndrome. My project aims to understand the molecular pathophysiology of Alpers-Huttenlocher syndrome and inform the development of effective therapies.
Investigating the role of POLG mutations in Alpers syndrome
Alpers syndrome is a rare autosomal recessive infantile mitochondrial disease, mainly characterised by intractable seizures/epilepsy, psychomotor delay and liver dysfunction/failure. The underlying genetic defect involves mutations in polymerase gamma (POLG), the only known DNA polymerase in mammalian mitochondria.
POLG mutations in Alpers cause, through yet unidentified mechanisms. mitochondrial DNA depletion (quantitative loss of copy number) and mitochondrial DNA deletions in clinically affected tissue. This leads to compromised energy production from the oxidative phosphorylation machinery with consequent development of disease. Seizures and liver failure are the predominant manifestations of Alpers, although the underlying mechanisms have been poorly characterised.
The aim of my project is to understand the molecular mechanisms governing seizure onset and liver involvement through the characterisation of the mitochondrial phenotype and function in POLG-mutant human cell lines. This will provide insight to the pathology of Alpers and Alpers-like disease and may inform the development of effective therapies.
Sponsor/funder: Ryan Stanford Appeal