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Title: Lysosome-related organelles : an investigation into clinical disorders of endothelial cells and platelets
Author: Westmoreland, D. A.
ISNI:       0000 0004 7225 1239
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Lysosome-related organelles (LROs) are a heterogeneous group of organelles that have important functions in a number of specialised cell types. LROs, despite their distinct features and morphology, have been grouped together due to the observation that they are simultaneously functionally perturbed by single mutations in a number of genetic disorders, yet as a group they are still poorly understood. Firstly, it was investigated whether the genes that are important for the formation/maturation of other LROs can also affect Weibel-Palade bodies (WPBs) an endothelial LRO that is critical to haemostasis and inflammation. In the genetic disorder Hermansky Pudlak syndrome (HPS) a number of LROs are affected, but the effect of these mutations on WPBs is not yet established. It was investigated whether these genes are indeed important for the biogenesis and function of WPBs, potentially revealing a new aspect of the disease phenotype. siRNA ablation in human endothelial cells of genes identified as involved in LRO biogenesis proved to give inconclusive results as to their importance in WPB formation and function. Secondly, the understanding of LRO-related genetic disorders would be aided by an improvement in diagnostics. The diagnosis of platelet storage disorders (PSDs) is currently limited to the observation of symptoms (e.g. a bleeding disorder or albinism) that are often shared with other, more common diseases. Most HPS patients are initially misdiagnosed and many see 4 to 6 specialists before being correctly identified. I investigated whether Super Resolution Microscopy, allowing images to be taken with a higher resolution than the diffraction limit (< 200 nm), has the potential for improving the imaging of platelet granules and thereby the diagnosis and characterisation of LRO-related disorders. The use of structured illumination microscopy, coupled with automated image analysis bioinformatics allowed for a highly efficient differentiation between control and patient platelets.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available