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 11 of 11 for “"Patient fibroblasts"”.
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The Role of FBXO7 in Mitochondrial Biology and Parkinson's Disease
… CRISPR knockout SH-SY5Y cell lines, primary patient fibroblasts with a FBXO7 mutation, and MEFs and tissues from a Fbxo7 KO mouse. My analysis of fibroblasts from a patient without FBXO7 expression revealed several interesting phenotypes. Briefly, the patient fibroblasts proliferated slower …
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Characterisation of LITAF, a protein associated with Charcot-Marie-Tooth disease type 1C
… the assays were discussed. Lastly, with patient fibroblasts available in our lab, disease phenotypes were analysed using two types of imaging technique: transmission electron microscopy (TEM) (in collaboration with J. Edgar) and immunofluorescence microscopy. Swollen vacuoles were …
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Base editing of Galactose-1-Phosphate Uridylyl Transferase as a novel gene therapy approach to treat Q188R mutation in a cellular model of Classic Galactosemia
… to restore the original GALT sequence in GALT KO patient cells. We observed base editing, but at a very low level of <2% from transducing homozygous Q188R patient fibroblasts with an adenovirus construct carrying the base editor. Further, we optimized a GALT activity assay that can detect GALT …
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Cytosolic sphingolipids and lysosome reactivation in neurodegenerative diseases
… in Gaucher/Parkinson's and various other LSD patient fibroblasts. Then it studies whether these defects can be corrected by altering cytosolic GlcCer. Chapter 3 shows decreased MCS between the ER/lysosomes, increased MCS between lysosomes/ the mitochondria in NPCD, and investigates if …
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Developing Red Fluorescent Zn2+ Sensors and Characterizing Zn2+ Homeostasis in Mucolipidosis Type IV Disease
… and localization of 10 different TRPML1 patient mutants. Furthermore, we quantify Zn<sup>2+</sup> concentrations in the cytosol, lysosomes, and mitochondria in MLIV patient fibroblasts. We found that mitochondrial Zn<sup>2+</sup> concentrations are significantly higher in MLIV cells. …
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Sensing Foreign DNA: The Role of DNA-PKcs in Human Anti-viral Innate Immunity
… to dissect the DNA sensing pathway in human fibroblasts. In these human cells DNA-PKcs was found to be essential for the production of type I interferon via the STING pathway in response to DNA and DNA virus infection and we found that the kinase activity of DNA-PKcs was not required for this …
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Bioenergetic Evaluation of Site-specific Keloid and FKN Fibroblasts
… at a cellular level in these two conditions. Patient-derived tissue biopsies were used for fibroblast cell culture models, in which cell analysis was carried out to assess phenotype and different parameters of bioenergetic cellular behaviour. In addition to FKN and the intra- and peri-lesional …
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Why do allelic variants of the mitochondrial chaperone SCO1 cause clinically heterogeneous forms of disease? A mouse model and proximity ligation study
… their wild-type littermates and, unlike SCO1 patients, did not exhibit an outward failure to thrive. Biochemical, molecular and elemental tissue analyses revealed that the murine heart was most susceptible to loss of SCO1 function. However, Sco1 M227V brains exhibited a significant, combined …
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Modelling neuronal mitochondrial aminoacyl-tRNA synthetase defects
… research relies primarily on non-human models or patient-derived fibroblasts that do not recapitulate the tissue-specific complexities of the nervous system. Here, I address this unmet need by applying tissue-specific human models of the nervous system to investigate the cellular impact of AARS2, …
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Investigating the pathogenesis and therapy of Friedreich Ataxia
… of novel cell culture systems, including primary fibroblasts, neural stem cells (NSC) and splenocytes, from FRDA YAC transgenic mouse models (YG8 and YG22). Then, I have shown the differentiation of NSCs into neurons, oligodendrocytes and astrocytes. The presence of these cells was confirmed by …
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The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes
… inherited mitochondrial diseases directly from patient DNA by facilitating the identification of potential candidate genetic defects in either nuclear or mitochondrial genomes. In such a manner, two compound heterozygous sequence variants in COA7, which encodes a putative cytochrome c oxidase …