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Title: Mitochondrial respiratory chain dysfunction in human pathology : investigation, pathogenicity and treatment
Author: Taylor, Robert William
ISNI:       0000 0001 2411 0982
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2012
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The work presented in this thesis comprises 100 peer-reviewed publications, mostly original research papers but some key review articles are included, which highlight my ongoing research in understanding the role of mitochondrial respiratory chain dysfunction and mitochondrial DNA (mtDNA) mutation in human pathologies over a twenty year period, and in no small part have contributed to the development of my laboratory as a national referral centre in the UK for diagnostic biochemical and molecular genetic testing, funded by the NHS Specialist Commissioners. A significant proportion (at least 50%) of all the papers which are included in this application are either first author or senior author publications. Mitochondrial respiratory chain disease exhibits marked clinical and genetic heterogeneity, often requiring the study of clinically-relevant, post-mitotic tissues to make a diagnosis which in many cases is made difficult on account of the peculiarities of mitochondrial genetics. Understanding this phenotypic diversity and elucidating the basic molecular mechanisms leading to cellular dysfunction continues to be challenging, with progress in the development of curative therapies hampered by our inability to manipulate the mitochondrial genome, and difficulties in obtaining alternative models of disease other than patients with pathogenic mtDNA mutations. . In an attempt to submit a cohesive application, the papers have been organised into relevant sections, beginning with general reviews of the clinical, biochemical and molecular features of mitochondrial genetic disease (Section A) followed by sections on the investigation and laboratory diagnosis of mitochondrial disease including epidemiology (Sections 8-0). The largest collection of papers document the molecular investigation of mitochondrial disorders, many describing novel mutations and disease mechanisms associated with both mtDNA- encoded and nuclear mitochondrial genes (Sections E-K). The next section describe studies investigating the role of somatic mtDNA abnormalities in neurodegenerative disease, cancer and ageing pathologies - including marking stem cell populations (Section L) - before a series of original research articles and invited reviews that focus on pharmacological and gene therapy strategies for the treatment of patients with mtDNA disease (Section M).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available