Understanding skeletal muscle adaptation in health and chronic disease: a multi-omics based systems biology perspective

Davidsen, Peter Kåre (2016). Understanding skeletal muscle adaptation in health and chronic disease: a multi-omics based systems biology perspective. University of Birmingham. Ph.D.

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Abstract

Mammalian skeletal muscle has a major impact on whole-body metabolic homeostasis. Hence, maintenance of a metabolically active muscle mass is key for optimal health. Notably, both muscle function and mass are profoundly negatively affected by environmental factors such as chronic smoking and physical inactivity.

RNA abundance integrates genetic, epigenetic and environmental influences. Therefore, while true understanding of physiological adaptation likely require the integration between multi-level datasets, the transcriptome represents a powerful investigative tool in determining the underlying molecular mechanisms behind complex phenotypic traits.

The overarching aim of this thesis was to evaluate, using omics-based systems biology approaches, the global regulation of RNAs during exogenous modulation of mammalian muscle phenotype in order to characterize local homeostatic processes as well as identify robust biomarker signatures.

The first part of this thesis deals with smoke-induced peripheral muscle wasting.
Initially, biological domain knowledge is used to validate a pre-clinical smoking model. Then, specific cytokines are statistically linked to limb muscle energy metabolism; a testable hypothesis supported by both animal and human data.

The second part deals with the development of ‘molecular predictors’ of endurance training adaptability. Two complex clinically relevant traits are considered, namely whole-body insulin sensitivity and plasma triglyceride content. Promisingly, quantitative multi-gene predictors of response to training for both traits of interest were developed.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):