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The characterisation of gene regulatory networks in regeneration employing in silico methods for RNASeq data

Richards Michelle, Shola (2019) The characterisation of gene regulatory networks in regeneration employing in silico methods for RNASeq data. PhD thesis, University of Leeds.

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In non-healing, ‘chronic’ wounds, tissue repair and regeneration fails, potentially leading to the loss of limbs or even death. The current lack of understanding of the biological principles leading to chronic wounds has resulted in ineffective therapeutic strategies. This thesis comprises studies to gain a better understanding of healing; one is the first to fully characterise a chronic wound utilising transcriptome data, leveraging the knowledge of various diseases that cause chronic wounds. The thesis focuses on the transcriptome of two tissues with disparate healing responses: skeletal muscle, a model that fully regenerates; and dermal tissue, in which regeneration is challenged and at times fails. GenIIPhen, a computational tool, was developed to contextualise and support experimental data utilising publicly available genetic and phenotypic data from various model organisms. The analysis of skeletal muscle revealed that non-coding RNAs may play a fundamental role in the healing process. In addition, the up-regulation of genes related to inflammation, particularly IL1b, was also observed in aged mice—the model used to represent dysregulated healing in skeletal muscle. In dermal wounds, inflammation, immune response, senescence, angiogenesis, and genes/pathways indicating a response to the presence of microbial colonies were up-regulated in chronic wounds. The observed down-regulation of keratinisation processes in these tissues suggests transition between the later phases of proliferation; granulation tissue formation is disrupted. These findings allowed selection of candidate biomarkers and a ‘signature’ which may play pivotal roles in the regulation or dysregulation of the wound-healing process. Overall, the results reported here demonstrate that large transcriptome differences exist between normal and dysregulated healing; they also suggest that non-coding RNAs play a substantial role in the regenerative process. This represents the first in-depth characterisation of chronic wounds of its kind, supporting a better understanding of the pathways and processes perturbed in non-healing wounds. These findings, combined with data currently in the public domain, will empower clinicians and scientists to more effectively assess and treat chronic wounds.  

Item Type: Thesis (PhD)
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute for Molecular and Cellular Biology (Leeds)
Depositing User: shola richards
Date Deposited: 28 Nov 2019 16:38
Last Modified: 28 Nov 2019 16:38
URI: http://etheses.whiterose.ac.uk/id/eprint/25063

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