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Title: The mitochondrial redox regulation of steroidogenesis
Author: Griffin, Aliesha
ISNI:       0000 0004 5361 0224
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
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Mitochondrial steroidogenic cytochrome P450 (CYP) enzymes rely on electron transfer from the redox partner ferredoxin for catalytic activity. Previous in vitro data suggests these co-factors are key regulators of CYP enzyme activity. However, this has never been studied in vivo. Zebrafish have emerged as model to study human steroidogenesis as they have conserved steroidogenic genes, molecular mechanisms and endocrine tissues. This project aimed to establish zebrafish as an in vivo model for endocrine development and its disorders, and to investigate the influence of mitochondrial redox regulation on steroid hormone production. This study involved the identification and characterisation of zebrafish mitochondrial steroidogenic CYP enzymes and their ferredoxin co-factors. Through implementation of recent genomic editing methods including Transcription Activator-Like Effector Nucleases (TALENs) and the Clustered Regulatory Interspaced Short Palindromic Repeat Cas9 nuclease (CRISPR/Cas9) system, and steroid hormone analysis from whole zebrafish extracts by liquid chromatography/tandem mass spectrometry, essential mitochondrial redox components required for zebrafish glucocorticoid production were identified. Overall, this work has helped established zebrafish as a model to study the pathophysiological consequences of steroid hormone disease and provided insights into the mechanism of mitochondrial redox regulation of steroid hormone production.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology