Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 26 for “"Mitochondrial Disease"”.
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The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes
Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders typically associated with abnormal oxidative phosphorylation (OXPHOS). In recent years, next generation sequencing technologies have allowed for accurate genetic diagnoses of inherited mitochondrial diseases …
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MIR-181A/B INHIBITION AS A NEW STRATEGY FOR MITOCHONDRIAL DISEASE TREATMENT
Mitochondrial diseases (MDs) are a group of rare inherited disorders caused by defective oxidative phosphorylation (OXPHOS) and defined by a wide range of clinical phenotypes. MDs show extreme genetic heterogeneity, which makes the development of efficient treatments particularly difficult. Indeed, …
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AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease
… kinase (AMPK) is a kinase that can initiate mitochondrial biogenesis and mitophagy. We hypothesized that treating cells harbouring low numbers of mtDNA with an AMPK activator (5-Aminoimidazole-4-carboxamide ribonucleoside; AICAR) would ameliorate the decrease in ETC activity and improve mtDNA …
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Investigating Cell-Type-Specific Vulnerability in Mitochondrial Disease Using Stem Cell-Derived Neuronal Models
Mitochondrial diseases are a group of widely heterogeneous genetic disorders that primarily affect tissues with high energy demands. Although disruption of oxidative phosphorylation is a shared hallmark across these conditions, their clinical manifestations display remarkable tissue specificity, …
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Creating CRISPR-Cas9 genome edited iPSC lines to model a patient-specific mutation in mitochondrial disease
Mitochondrial aminoacyl tRNA-synthetases (mt-aaRS) catalyse the charging of tRNAs with their cognate amino acids in mitochondria. Mutations in mt-aaRS cause tissue-specific mitochondrial diseases, especially affecting tissues with high energy expenditure like the nervous system, heart, and kidneys. …
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Computer modelling of metabolic adaptions during mitochondrial dysfunction and machine learning to predict novel mitochondrial disease genes
… This thesis investigates two main causes of mitochondrial dysfunction: mitochondrial toxicity arising from side-effects of drugs; and mitochondrial diseases arising from defects in nuclear-encoded genes. Novel chemical entities being developed as drug leads are screened for cellular toxicity …
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A metabolic profiling approach to human disorders of energy metabolism
… in parts of this network causes human disease - both rare, inherited disorders and common diseases such as diabetes mellitus. The study of metabolic disease depends upon quantitative methods which are traditionally custom-tailored to a given compound. Recent advances in technologies …
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Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction
… consequences on human physiology and health. Mitochondrial disorders are the most common inborn errors of metabolism, affecting approximately 1 in 5000 live births. Patients can present in infancy or adulthood with symptoms affecting multiple organ systems including blindness, deafness, muscle …
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Investigation into Tissue-Specific Mechanisms of Mitochondrial Dysfunction: Models of SUCLA2 Deficiency and a Screen for Potential Genetic Modifiers
With no currently effective treatments available, mitochondrial diseases are one of the most common forms of inherited multisystem disease. Primary disorders of the mitochondria affect an estimated 1 in 4,300 people with typical onset in early childhood. Mitochondrial disorders are classically …
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Modelling and investigating treatments of childhood inherited mitochondrial diseases in zebrafish.
Mitochondrial DNA depletion syndromes (MDDS) are a group of severe, individually rare, clinically heterogeneous disorders that primarily affect children. Affected tissues tend to be those with a high energy demand such as the central nervous system and skeletal muscle. MDDS stem from disruption to …
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Defining the cellular and molecular mechanism of maternally inherited hearing loss
Mitochondrial dysfunction causes moderate to profound hearing loss both in isolation and as a feature of multi-systemic mitochondrial disease. The m.1555A>G mitochondrial DNA (mtDNA) variant is associated with a predisposition to aminoglycoside ototoxicity and maternally inherited non-syndromic …
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Pathogenesis and Therapy of Mitochondrial Diseases
… mitochondria have retained their own genome the mitochondrial DNA, mtDNA. In mammals, replication of mtDNA is ensured by the DNA polymerase POLγ, which is composed by one catalytic subunit POLγA and two accessory subunits POLγB. Mutations in the nuclear-encoded POLG gene, coding for POLγA, are a …
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Mitochondrial genome engineering in the murine germline using designer nuclease technology
… are encoded in the nuclear genome. However, the mitochondrial genome, which is a circular, multi-copy genome of roughly 17 kb in size, also encodes for 13 polypeptide genes that form key components of the OXPHOS complexes, along with the 22 tRNA genes and 2 rRNA genes required for their …
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The Development Of Mems-Based Implantable Oxygen Sensing Systems
… of in vivo biological effects, ranging from mitochondrial disease to tissue engineering/regenerative medicine. Existing electrochemical oxygen sensors are permanent systems applicable to short-term intraoperative use; devices are extracted before wound closure. Development of biocompatible …
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Comparative phylogenetic exploration of the human mitochondrial proteome: Insights into disease and metabolism
… from ATP synthesis to apoptosis. Changes in mitochondrial function are associated with many diseases, as well as ‘natural’ processes like ageing. Mitochondria have a unique evolutionary origin, as the result of an endosymbiotic relationship between a bacterium and an archaeal cell. Therefore, …
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Using molecular approaches to understand Complex I deficiency in mouse models
… a major electron entry point to the mitochondrial respiratory chain, couples electron transfer from NADH to ubiquinone to proton pumping across the mitochondrial inner membrane, and generates the proton motive force that drives ATP synthesis and transport processes. The ~1 MDa …
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Bioinformatic Approaches to Study Mitochondrial DNA Heteroplasmy
… of their own small, circular DNA, known as mitochondrial DNA(mtDNA). Mutations in mtDNA can be maternally inherited or somatic, when they occur after fertilisation. There are mechanisms at both the extra- and intracellular levels to prevent the transmission of these mutations across …
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Optimisation and validation of tools for in situ visualisation of heteroplasmic mtDNA variants.
… heteroplasmy is the leading cause of adult-onset mitochondrial disease, affecting 1 in 5,000 people in the United Kingdom. It plays a role in neurodegenerative disorders like Alzheimer’s and Parkinson’s disease. Despite their importance, the processes that cause this expansion of mutant mtDNA are …
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Characterisation of Mitochondrial Dynamics and Mitochondrial DNA Inheritance in Drosophila melanogaster
… organelles and there is mounting evidence that mitochondrial dysfunction is linked to a variety of diseases. During spermatogenesis in <i>Drosophila melanogaster</i>, the organisation of mitochondrial networks is altered during each stage of development. This thesis is focused on a novel …
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The role of the mitofusins in adipose tissue
Monogenic mitochondrial disease is known to cause tissue-selective manifestations, typically affecting the nervous system, liver, and muscle. However, until recently, there was relatively little human genetic evidence for a role of mitochondria in disorders of energy balance (i.e. weight) or …
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