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A network inference approach to understanding musculoskeletal disorders

Turan, Nil (2014)
Ph.D. thesis, University of Birmingham.

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Abstract

Musculoskeletal disorders are among the most important health problem affecting the quality of life and contributing to a high burden on healthcare systems worldwide. Understanding the molecular mechanisms underlying these disorders is crucial for the development of efficient treatments.

In this thesis, musculoskeletal disorders including muscle wasting, bone loss and cartilage deformation have been studied using systems biology approaches. Muscle wasting occurring as a systemic effect in COPD patients has been investigated with an integrative network inference approach. This work has lead to a model describing the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. This model has shown for the first time that oxygen dependent changes in the expression of epigenetic modifiers and not chronic inflammation may be causally linked to muscle dysfunction.

Bone and cartilage deformation observed in ageing, arthritis and multiple myeloma (MM) patients have also been investigated by using a novel modularization approach developed within this thesis. This methodology allows integration of multi-level dataset with large interaction networks. It aims to identify sub-networks with genes differentially expressed between experimental conditions that are co-regulated across samples in different biological systems. This study has identified several potential key players such as Myc, DUSP6 and components of Notch that could enhance osteogenic differentiation in MM patients.

In conclusion, this thesis present the effectiveness of systems biology approaches in understanding complex diseases and these approaches could be applied for studying other systems and datasets.

Type of Work:Ph.D. thesis.
Supervisor(s):Falciani, Francesco and Hotchin, Neil
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QM Human anatomy
QP Physiology
QR Microbiology
Institution:University of Birmingham
ID Code:4863
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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