Personal Biography
I was awarded my B.Sc (Hons) in Biological Sciences from the University of East Anglia in 1983. I moved to the Australian National University in Canberra to study for a Ph.D in Microbial Genetics (and learn to surf) under the supervision of Professors Frank Gibson and Graeme Cox, graduating in 1988. Following a postdoctoral position with Professor Rod Capaldi at the Institute of Molecular Biology in Eugene Oregon USA, where I gained my lifelong interest in mitochondria and mitochondrial disease, I successfully applied for a Lister Institute Fellowship in 1990. This allowed me to return to the UK, where I established my laboratory at Newcastle University to study the molecular mechanisms of mitochondrial gene expression and disease. I have been employed by Newcastle University since that date, being awarded a Personal Chair in 2000. From my close interaction with Professor Turnbull, the Mitochondrial Research Group was initiated. This has expanded enormously and led to formation of the Wellcome Trust Centre for Mitochondrial Research in 2012. I was appointed Director of the Institute for Cell and Molecular Biosciences in 2012.
Research Biography
My postgraduate studies were on the function of the ATP synthase in eubacteria. It was therefore not such a large step to studying oxidative phosphorylation in man, which I started in the US in 1988. Mutations of the mitochondrial genome (mtDNA) were shown to cause disease and my main research topic since this time has been into determining the molecular mechanisms that underlie expression of this genome in man and searching for a cure for these disorders. This has proved to be particularly complicated, as it is not yet possible to transfect mammalian mitochondria in intact cells and there is no faithful reconstituted system for studying mitochondrial protein synthesis. The multi-copy nature of mtDNA has also led to a fascination with mitochondrial genetics and transmission. Studying pathogenic mutations, both in the nucleus and in mtDNA, that result in defects of mitochondrial gene expression, has helped us understand far more about these complex mechanisms and through these insights we hope to be able to offer treatments that are currently not available for the majority of patients with mitochondrial disease.
Awards, honours and professional service
1998 Ph.D John Curtin School of Medical Research, Australian National University
1996-present Member of the Lister Institute of Preventive Medicine
1997 Henry Wellcome Commemorative Award for Innovative Research
1998-present Member, Biochemical Society
1997 Member, Advisory panel to the French Government on use of nucleoside analogues in AIDS research
1998 Erskine Prize, University of Canterbury, Christchurch New Zealand
2000 Professor of Molecular Neuroscience, Newcastle University
2001-2012 Scientific advisory panel for Ataxia UK
2005-2009 MRC College of Experts
2008-2011 BBSRC Pool of Experts
2011-present Finnish Academy of Science Scientific Review Board 2011-present
2012 Director, Institute for Cell and Molecular Biosciences, Newcastle University
2012 Royal Swedish Academy of Science Evaluation for Goran Gustafsson Prize
2013 -Research Council of Norway Scientific Review Board 2013
Recent Key Publications
Publications
, 2016. Applying the Airbrakes: Treating Mitochondrial Disease with Hypoxia. Mol Cell 62(1):5-6
, 2015. A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency. Eur J Hum Genet 23(7):935-9
, 2015. The presence of highly disruptive 16S rRNA mutations in clinical samples indicates a wider role for mutations of the mitochondrial ribosome in human disease. Mitochondrion 25:17-27
, 2015. Response to "Ribosome Rescue and Translation Termination at Non-standard Stop Codons by ICT1 in Mammalian Mitochondria". PLoS Genet 11(6):e1005227
, 2015. Mutations causing mitochondrial disease: What is new and what challenges remain? Science 349(6255):1494-9
, 2015. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population. Brain 138(Pt 12):3503-19
, 2015. Potential compounds for the treatment of mitochondrial disease. Br Med Bull 116:5-18
, 2014. Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency. Biochim Biophys Acta 1842(1):56-64
, 2014. The role of TDP1 and APTX in mitochondrial DNA repair. Biochimie 100:121-4
, 2014. The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential. Hum Mol Genet 23(4):949-67
, 2014. Human mitochondrial leucyl tRNA synthetase can suppress non cognate pathogenic mt-tRNA mutations. EMBO Mol Med 6(2):183-93
, 2014. Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy? EMBO Mol Med 6(6):705-7
, 2014. Overcoming stalled translation in human mitochondria. Front Microbiol 5:374
, 2014. A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression. Hum Mol Genet 23(23):6345-55
, 2014. Mitochondrial protein synthesis: figuring the fundamentals, complexities and complications, of mammalian mitochondrial translation. FEBS Lett 588(15):2496-503
, 2013. GRSF1 regulates RNA processing in mitochondrial RNA granules. Cell Metab 17(3):399-410
, 2013. Human pentatricopeptide proteins: only a few and what do they do? RNA Biol 10(9):1433-8
, 2013. REXO2 is an oligoribonuclease active in human mitochondria. PLoS One 8(5):e64670
, 2013. Analysis of 953 human proteins from a mitochondrial HEK293 fraction by complexome profiling. PLoS One 8(7):e68340
, 2012. Recombinant human MDM2 oncoprotein shows sequence composition selectivity for binding to both RNA and DNA. Int J Oncol 40(3):851-9
, 2012. C7orf30 specifically associates with the large subunit of the mitochondrial ribosome and is involved in translation. Nucleic Acids Res 40(9):4040-51
, 2012. Exploring our origins--the importance of OriL in mtDNA maintenance and replication. EMBO Rep 13(12):1038-9
, 2012. The mystery of mitochondrial RNases. Biochem Soc Trans 40(4):865-9
, 2011. 175th ENMC International Workshop: Mitochondrial protein synthesis in health and disease, 25-27th June 2010, Naarden, The Netherlands. Neuromuscul Disord 21(2):142-7
, 2011. DNA repair in organelles: Pathways, organization, regulation, relevance in disease and aging. Biochim Biophys Acta 1813(1):186-200
, 2011. Altering the balance between healthy and mutated mitochondrial DNA. J Inherit Metab Dis 34(2):309-13
, 2011. NOA1 is an essential GTPase required for mitochondrial protein synthesis. Mol Biol Cell 22(1):1-11
, 2011. Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency. Brain 134(Pt 1):183-95
, 2011. DNA delivery to mitochondria: sequence specificity and energy enhancement. Pharm Res 28(11):2871-82
, 2011. Termination of protein synthesis in mammalian mitochondria. J Biol Chem 286(40):34479-85
, 2011. Mitochondrial transfection for studying organellar DNA repair, genome maintenance and aging. Mech Ageing Dev 132(8-9):412-23
, 2011. Mitochondrial transformation: time for concerted action. EMBO Rep 12(6):480-1
, 2011. Designing an organellar postal service: delivery of macromolecules to mitochondria in intact cells. Mol Ther 19(8):1404-5
, 2010. A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. EMBO J 29(6):1116-25
, 2010. Mitochondrial DNA mutations affect calcium handling in differentiated neurons. Brain 133(Pt 3):787-96
, 2010. Mechanism of neurodegeneration of neurons with mitochondrial DNA mutations. Brain 133(Pt 3):797-807
, 2010. Age-associated mitochondrial DNA mutations lead to small but significant changes in cell proliferation and apoptosis in human colonic crypts. Aging Cell 9(1):96-9
, 2010. Membrane association of mitochondrial DNA facilitates base excision repair in mammalian mitochondria. Nucleic Acids Res 38(5):1478-88
, 2010. Hungry codons promote frameshifting in human mitochondrial ribosomes. Science 327(5963):301
, 2010. Targeting of the cytosolic poly(A) binding protein PABPC1 to mitochondria causes mitochondrial translation inhibition. Nucleic Acids Res 38(11):3732-42
, 2010. Human ERAL1 is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit. Biochem J 430(3):551-8
, 2010. Could successful (mitochondrial) networking help prevent Huntington's disease? EMBO Mol Med 2(12):487-9
, 2010. Human mitochondrial mRNAs--like members of all families, similar but different. Biochim Biophys Acta 1797(6-7):1081-5
, 2010. Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am J Hum Genet 87(5):655-60
, 2010. Translation termination in human mitochondrial ribosomes. Biochem Soc Trans 38(6):1523-6
, 2010. PNPASE regulates RNA import into mitochondria. Cell 142(3):456-67
, 2010. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature 465(7294):82-5
, 2010. Terminating human mitochondrial protein synthesis: a shift in our thinking. RNA Biol 7(3):282-6
, 2009. Developing a genetic approach to investigate the mechanism of mitochondrial competence for DNA import. Biochim Biophys Acta 1787(5):320-7
, 2009. Probing the orientation of yeast VDAC1 in vivo. FEBS Lett 583(4):739-42
, 2009. Transmitochondrial embryonic stem cells containing pathogenic mtDNA mutations are compromised in neuronal differentiation. Cell Prolif 42(4):413-24
, 2009. Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy. Brain 132(Pt 11):3165-74
, 2008. Overexpression of human mitochondrial valyl tRNA synthetase can partially restore levels of cognate mt-tRNAVal carrying the pathogenic C25U mutation. Nucleic Acids Res 36(9):3065-74
, 2008. Nature of mitochondrial DNA deletions in substantia nigra neurons. Am J Hum Genet 82(1):228-35
, 2008. Polyadenylation and degradation of mRNA in mammalian mitochondria: a missing link? Biochem Soc Trans 36(Pt 3):517-9
, 2008. What causes mitochondrial DNA deletions in human cells? Nat Genet 40(3):275-9
, 2008. Progress and prospects: gene therapy for mitochondrial DNA disease. Gene Ther 15(14):1017-23
, 2008. PPR (pentatricopeptide repeat) proteins in mammals: important aids to mitochondrial gene expression. Biochem J 416(1):e5-6
, 2008. The human mitochondrial ribosome recycling factor is essential for cell viability. Nucleic Acids Res 36(18):5787-99
, 2007. Differential selection of acridine resistance mutations in human DNA topoisomerase IIbeta is dependent on the acridine structure. Mol Pharmacol 71(4):1006-14
, 2007. How do mammalian mitochondria synthesize proteins? Biochem Soc Trans 35(Pt 5):1290-1
, 2006. Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement. Neuropathol Appl Neurobiol 32(4):359-73
, 2006. Transmission of mitochondrial DNA disorders: possibilities for the future. Lancet 368(9529):87-9
, 2006. Natural competence of mammalian mitochondria allows the molecular investigation of mitochondrial gene expression. Hum Mol Genet 15(1):143-54
, 2006. Production of transmitochondrial cybrids containing naturally occurring pathogenic mtDNA variants. Nucleic Acids Res 34(13):e95
, 2006. Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNALeu(UUR)) gene. Nucleic Acids Res 34(22):6404-15
, 2006. Phage display selection of efficient glutamine-donor substrate peptides for transglutaminase 2. Protein Sci 15(11):2466-80
, 2006. Mitochondrial DNA clonality in the dock: can surveillance swing the case? Trends Genet 22(11):603-7
, 2005. Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability. Nucleic Acids Res 33(1):376-87
, 2005. Accumulation of Nav1 mRNAs at differentiating postsynaptic sites in rat soleus muscles. Mol Cell Neurosci 28(4):694-702
, 2004. Identification of the RAG-1 as a suitable mouse model for mitochondrial DNA disease. Neuromuscul Disord 14(5):329-36
, 2004. Neuropathological aspects of mitochondrial DNA disease. Neurochem Res 29(3):505-11
, 2004. Mitochondrial DNA deletion in "identical" twin brothers. J Med Genet 41(2):e19
, 2004. Functional polypeptides can be synthesized from human mitochondrial transcripts lacking termination codons. Biochem J 377(Pt 3):725-31
, 2004. Messenger RNA stability in mitochondria: different means to an end. Trends Genet 20(6):260-7
, 2004. Strategies for treating disorders of the mitochondrial genome. Biochim Biophys Acta 1659(2-3):232-9
, 2004. Proving pathogenicity: when evolution is not enough. Am J Med Genet A 131(1):107-8; author reply 109-10
, 2004. Sporadic mitochondrial myopathy due to a new mutation in the mitochondrial tRNASer(UCN) gene. Neuromuscul Disord 14(7):417-20
, 2004. Nuclear DNA-encoded tRNAs targeted into mitochondria can rescue a mitochondrial DNA mutation associated with the MERRF syndrome in cultured human cells. Hum Mol Genet 13(20):2519-34
, 2003. A homoplasmic mitochondrial transfer ribonucleic acid mutation as a cause of maternally inherited hypertrophic cardiomyopathy. J Am Coll Cardiol 41(10):1786-96
, 2003. Mismatch repair activity in mammalian mitochondria. Nucleic Acids Res 31(3):1052-8
, 2003. Specific targeting of a DNA-alkylating reagent to mitochondria. Synthesis and characterization of [4-((11aS)-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-on-8-oxy)butyl]-triphenylphosphonium iodide. Eur J Biochem 270(13):2827-36
, 2003. Changes in the human mitochondrial genome after treatment of malignant disease. Mutat Res 525(1-2):19-27
, 2003. Bridging PNAs can bind preferentially to a deleted mitochondrial DNA template but replication by mitochondrial DNA polymerase gamma in vitro is not impaired. Biochim Biophys Acta 1629(1-3):73-83
, 2003. Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria. Hum Mol Genet 12(18):2341-8
, 2003. Synthesis of trifunctional PNA-benzophenone derivatives for mitochondrial targeting, selective DNA binding, and photo-cross-linking. Bioconjug Chem 14(5):962-6
, 2003. Why do mammalian mitochondria possess a mismatch repair activity? FEBS Lett 554(1-2):6-9
, 2002. Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutation. Nat Genet 30(2):145-6
, 2002. A roundabout route to gene therapy. Nat Genet 30(4):345-6
, 2002. A high frequency of mtDNA polymorphisms in HeLa cell sublines. Mutat Res 501(1-2):19-28
, 2001. Targeting peptide nucleic acid (PNA) oligomers to mitochondria within cells by conjugation to lipophilic cations: implications for mitochondrial DNA replication, expression and disease. Nucleic Acids Res 29(9):1852-63
, 2001. An antigenomic strategy for treating heteroplasmic mtDNA disorders. Adv Drug Deliv Rev 49(1-2):121-5
, 2001. Fending off decay: a combinatorial approach in intact cells for identifying mRNA stability elements. RNA 7(3):435-44
, 2001. Inhibition of mitochondrial protein synthesis promotes autonomous regulation of mtDNA expression and generation of a new mitochondrial RNA species. FEBS Lett 494(3):186-91
, 2001. Targeting large molecules to mitochondria. Adv Drug Deliv Rev 49(1-2):189-98
, 2001. Analysis of European mtDNAs for recombination. Am J Hum Genet 68(1):145-153
, 2001. Linked oligodeoxynucleotides show binding cooperativity and can selectively impair replication of deleted mitochondrial DNA templates. Nucleic Acids Res 29(16):3404-12
, 2001. High-level mitochondriology at high altitude. Workshop on mitochondrial (dys-)function. EMBO Rep 2(12):1074-7
, 2001. Current perspectives in the treatment of mitochondrial DNA diseases. Funct Neurol 16(4 Suppl):89-96
, 2001. Sodium channel mRNAs at the neuromuscular junction: distinct patterns of accumulation and effects of muscle activity. J Neurosci 21(21):8456-63
, 2001. Might mammalian mitochondria merge? Nat Med 7(8):895-6
, 2001. Absence of expression from RNA internalised into electroporated mammalian mitochondria. Mol Genet Genomics 265(4):721-9
, 2000. Peptide nucleic acid and delivery to human mitochondria Gene Ther 7(9):813
, 2000. Does the mitochondrial transcription-termination complex play an essential role in controlling differential transcription of the mitochondrial DNA? Biochem Soc Trans 28(2):154-9
, 2000. Can paternal mtDNA be inherited? Lancet 355(9212):1290-1
, 2000. Identification of the NAD(+)-binding fold of glyceraldehyde-3-phosphate dehydrogenase as a novel RNA-binding domain. Biochem Biophys Res Commun 275(2):253-60
, 2000. In-vitro genetic modification of mitochondrial function. Hum Reprod 15 Suppl 2:79-85
, 2000. Mitochondrial DNA recombination. Lancet 356(9233):941
, 2000. The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both? Trends Genet 16(11):500-5
, 2000. Molecular basis for treatment of mitochondrial myopathies. Neurol Sci 21(5 Suppl):S909-12
, 1999. Mitochondrial DNA--all things bad? Trends Genet 15(3):91-3
, 1999. An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy. Am J Hum Genet 64(5):1330-9
, 1999. Conversion of a reporter gene for mitochondrial gene expression using iterative mega-prime PCR. Gene 230(2):241-7
, 1999. Nonrandom tissue distribution of mutant mtDNA. Am J Med Genet 85(5):498-501
, 1999. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet 23(2):147
, 1999. Peptide nucleic acid delivery to human mitochondria. Gene Ther 6(12):1919-28
, 1998. Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle. Ann Neurol 43(2):217-23
, 1998. MELAS and MERRF. The relationship between maternal mutation load and the frequency of clinically affected offspring. Brain 121 ( Pt 10):1889-94
, 1998. An essential guide to mtDNA maintenance. Nat Genet 18(3):199-200
, 1998. Genetic counseling and prenatal diagnosis for mtDNA disease. Am J Hum Genet 63(6):1908-11
, 1998. SCID mice containing muscle with human mitochondrial DNA mutations. An animal model for mitochondrial DNA defects. J Clin Invest 102(12):2090-5
, 1997. A novel mitochondrial tRNA phenylalanine mutation presenting with acute rhabdomyolysis. Ann Neurol 41(3):408-10
, 1997. Molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome. Ann Neurol 41(2):268-70
, 1997. Selective inhibition of mutant human mitochondrial DNA replication in vitro by peptide nucleic acids. Nat Genet 15(2):212-5
, 1997. Treatment of mitochondrial disease. J Bioenerg Biomembr 29(2):195-205
, 1997. Glutamate dehydrogenase: an organelle-specific mRNA-binding protein. Trends Biochem Sci 22(8):290
, 1997. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet 13(11):450-5
, 1997. Intracellular mitochondrial triplasmy in a patient with two heteroplasmic base changes. Am J Hum Genet 60(6):1430-8
, 1997. Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes. Brain 120 ( Pt 10):1713-21
, 1997. Reversal of a mitochondrial DNA defect in human skeletal muscle. Nat Genet 16(3):222-4
, 1996. Targeting proteins to mitochondria: is there a role for mRNA localization? Biochem Soc Trans 24(2):527-31
, 1995. Medium chain acyl-CoA dehydrogenase deficiency caused by a deletion of exons 11 and 12. Hum Mol Genet 4(4):747-9
, 1995. Human mitochondria: distinct organelles or dynamic network? Trends Genet 11(6):211-2
, 1995. The mRNA-binding protein COLBP is glutamate dehydrogenase. FEBS Lett 367(3):291-6
, 1995. Gene therapy for mitochondrial DNA defects: is it possible? Gene Ther 2(5):311-6
, 1994. Inhibition of mitochondrial protein synthesis promotes increased stability of nuclear-encoded respiratory gene transcripts. J Biol Chem 269(44):27322-8
, 1994. The tissue-specific RNA-binding protein COLBP is differentially regulated during myogenesis. Biochim Biophys Acta 1221(3):286-9
, 1994. Developmental regulation of tissue-specific isoforms of subunit VIa of beef cytochrome c oxidase. Biochim Biophys Acta 1188(3):391-7
, 1993. Neurologic complications of inherited mitochondrial abnormality, and neurologic consequences of inborn errors of metabolism. Curr Opin Neurol Neurosurg 6(3):429-36
, 1993. Isolation of a cDNA specifying subunit VIIb of human cytochrome c oxidase. Biochim Biophys Acta 1172(1-2):223-5
, 1993. Post-transcriptional regulation of tissue-specific isoforms. A bovine cytosolic RNA-binding protein, COLBP, associates with messenger RNA encoding the liver-form isopeptides of cytochrome c oxidase. J Biol Chem 268(14):10659-67
, 1993. Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA. A potential disease mechanism. J Biol Chem 268(26):19559-64
, 1993. Identification of bovine glutamate dehydrogenase as an RNA-binding protein. J Biol Chem 268(33):24523-6
, 1993. An antisense oligodeoxynucleotide approach to investigate the function of the nuclear-encoded subunits of human cytochrome c oxidase. Biochem Biophys Res Commun 196(1):328-35
, 1993. A microtiter plate assay for cytochrome c oxidase in permeabilized whole cells. Anal Biochem 214(1):45-9
, 1992. Hereditary disorders including mitochondrial diseases. Curr Opin Neurol Neurosurg 5(3):368-74
, 1990. Mutational analysis of the function of the a-subunit of the F0F1-APPase of Escherichia coli. Biochim Biophys Acta 1015(2):264-8
, 1989. Nucleotide sequence of the cDNA encoding subunit AED (VIB) of beef heart cytochrome c oxidase. Nucleic Acids Res 17(14):5845
, 1988. The proton pore in the Escherichia coli F0F1-ATPase: substitution of glutamate by glutamine at position 219 of the alpha-subunit prevents F0-mediated proton permeability. Biochim Biophys Acta 933(2):241-8
, 1987. The proton pore in the Escherichia coli F0F1-ATPase: a requirement for arginine at position 210 of the a-subunit. Biochim Biophys Acta 894(3):399-406
Publication list retrieved from NCBI using ImpactPubs
.
