Mathematical modelling of mammalian target of rapamycin following leucine ingestion

Author: 
Date created: 
2018-07-26
Identifier: 
etd19831
Keywords: 
MTOR
P70S6K
Leucine
Insulin
Protein synthesis
Mathematical modelling
Abstract: 

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.

Document type: 
Thesis
Rights: 
This thesis may be printed or downloaded for non-commercial research and scholarly purposes. Copyright remains with the author.
File(s): 
Senior supervisor: 
David Clarke
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.
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