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Sources of Funding
- Wellcome Trust
Routine clinical referrals
DNA diagnostics are carried out in collaboration with the Molecular Genetics Laboratories at the Churchill Hospital and detailed characterisation of defects of specific complexes in infants and young children by Dr GK Brown
Please follow this link to the form that should accompany any samples for DNA analysis that you send: Download Form
From 1st April 2007 this is funded by Rare Mitochondrial Disease Service for Adults and Children (NCG)
scholarships and prizes
1996 Royal Society University Research Fellowship
1992 Ronnie MacKeith prize, British Paediatric Neurological Association
1991 Wellcome Senior Research Fellowship in Clinical Science
1991 DM Oxford
1990 Medical Research Council Travelling Fellowship
1989 Sanofi Essay Prize (Advances in genetics and application to epilepsy)
1986 Action Research Training Fellowship
1982 MRCP (London)
1979 BM BCh Oxford
1977 Essay Prize in Pathology (Oxford Medical School)
1976 BA Oxford Physiological Sciences (Lady Margaret Hall, Oxford)
1975 College Scholarship (Lady Margaret Hall)
Professor of Mitochondrial Genetics
Research Interests include:
- Transmission and recurrence risks in mtDNA disease: The unique way in which mitochondrial DNA (mtDNA) is transmitted makes genetic counselling difficult. Dramatic changes in level of mutant mtDNA are attributable to a "genetic bottleneck" whereby a small number of mtDNAs become the founders for the offspring. We are studying the basis of this bottleneck in families and embryos, and are developing novel approaches to genetic counselling of mtDNA diseases, namely oocyte sampling and pre-implantation genetic diagnosis.
- Diseases of mtDNA maintenance: Control of mitochondrial copy number may be central to the pathogenesis of mtDNA disorders such as MtDNA depletion syndrome (MDS), Autosomal dominant Progressive External Ophthalmoplegia (AdPEO), Autosomal recessive Progressive External Ophthalmoplegia (ArPEO) and MyoNeuroGastroIntestinal Encephalomyopathy (MNGIE). These newly characterised mtDNA diseases are caused by mutations in autosomal genes, many of which are associated with a reduced quantity of defective mtDNA in affected tissues. We have therefore developed a method for quantitating the rate of mtDNA synthesis in cell lines derived from patients with these diseases. We are using this to study the 16189 variant, autosomally inherited defects in mtDNA maintenance and the basic science of mtDNA replication. We have also used this method to demonstrate consistent abnormalities in mtDNA synthesis in cell lines derived from such patients. Understanding the molecular mechanisms of these disorders may improve genetic counselling, and suggest novel therapies.
- MtDNA variants in common multi-factorial diseases: We demonstrated that a common polymorphism, the mtDNA "16189 variant" is a risk factor for low birth weight to placental ratio, type2 diabetes and other multifactorial disorders. Because the 16189 variant has arisen many times independently, these associations are likely to be causal and not due to a founder effect. We are studying the molecular basis for these associations, which imply interactions of nuclear and mitochondrial genomes.
A novel quantitative assay of mitophagy: Combining high content fluorescence microscopy and mitochondrial DNA load to quantify mitophagy and identify novel pharmacological tools against pathogenic heteroplasmic mtDNA.
Diot A. et al, (2015), Pharmacol Res, 100, 24 - 35
Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism.
Johnston IG. et al, (2015), Elife, 4
MtDNA segregation in heteroplasmic tissues is common in vivo and modulated by haplotype differences and developmental stage.
Burgstaller JP. et al, (2014), Cell Rep, 7, 2031 - 2041
Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse?
Chiaratti MR. et al, (2015), PLoS One, 10
Pigmentary retinopathy, rod-cone dysfunction and sensorineural deafness associated with a rare mitochondrial tRNA(Lys) (m.8340G>A) gene variant.
Gill JS. et al, (2017), Br J Ophthalmol, 101, 1298 - 1302
Genetic Counselling for Maternally Inherited Mitochondrial Disorders.
Poulton J. et al, (2017), Mol Diagn Ther, 21, 419 - 429
Erratum to: Genetic Counselling for Maternally Inherited Mitochondrial Disorders.
Poulton J. et al, (2017), Mol Diagn Ther, 21, 465 - 466
Modulating mitophagy in mitochondrial disease.
Dombi E. et al, (2017), Curr Med Chem
Clinicopathologic and molecular spectrum of RNASEH1-related mitochondrial disease.
Bugiardini E. et al, (2017), Neurol Genet, 3