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Title: The effects of the circadian clock on wound healing in skin
Author: Heath, K. S. C.
ISNI:       0000 0004 8497 6720
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Circadian rhythms are daily cycles of physiological functions which oscillate under the control of the circadian clock in order to coincide with the temporal demands of the light/dark cycle of the day. The importance of the integrity of the circadian clock in health and disease has emerged in recent years; perturbations of the circadian clock are associated with an increased risk of malignancy and metabolic syndrome. In this study, I aimed to examine whether RNAi modification of Bmal1, a core component of the circadian clock, could be used to improve wound healing. Chronic wounds are a global problem, in part caused by diabetes and ageing. Currently there is no effective pharmaceutical treatment; wound care by specialist nurses and physical methods such as compression bandages are the main course of action. Originally, the aim was to use DNA antisense to transiently knock down Bmal1. It became clear that this was having a toxic effect so several other approaches to knocking down Bmal1 expression were attempted. Ultimately, I used a lentiviral vector to transduce cells with an shRNA construct and also generated a Bmal1:luciferase reporter cell line to measure the oscillations of Bmal1 in vitro. Experiments using the reporter cells demonstrated that commonly used methods to synchronise the circadian clock in mammalian cells confirmed that these measures are unnecessary. The generation of cells with Bmal1 knockdown was only partially successful; however, an experiment using a heterogeneous population of Bmal1 knockdown cells indicates that this intervention reduces the migration rate of these cells in a scratch wound assay but further experiments are required to definitively determine the effects once a stable knockdown cell line has been established. If these preliminary results are true then the knockdown of Bmal1 is not likely to have a beneficial effect on wound healing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available