Mathematical modelling of mammalian target of rapamycin following leucine ingestion

Resource type
Thesis type
(Thesis) M.Sc.
Date created
Nutritional and hormonal factors primarily dictate skeletal muscle protein synthesis rates but how the whole-body dynamics of these factors mediate the cell signalling underlying protein translation is poorly understood. The purpose of my research was to develop and analyze a mathematical model of protein translational signalling in human skeletal muscle following leucine ingestion. The model incorporated the signalling proteins involved in the control of protein translation (e.g., IR/PI3K/AKT/mTOR) and was constructed by modifying amalgamated models of mTOR signalling and skeletal-muscle leucine kinetics. Initial model outputs agreed with tracer measurements and biopsy-based signalling data but failed to accurately simulate phospho-p70S6K. I proposed three hypotheses of p70S6K control and developed an expanded mTOR signalling network to improve the phospho-p70S6K kinetics. All proposed modifications failed to noticeably improve the accuracy of phospho-p70S6K simulations. My model represents a working hypothesis of protein translational control in skeletal muscle by nutritional and hormonal factors.
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Scholarly level
Supervisor or Senior Supervisor
Thesis advisor: Clarke, David
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