Dr. Thomas Sumner
My research dealt with uncertainty and sensitivity analysis in computational models of glucose homeostasis
(Supervisors: Prof David Bogle, Prof Liz Shephard). Computational
models of biological systems contain uncertainties in both their
quantitative (parameter values, initial conditions) and qualitative
(model structure and assumptions) inputs. Using models of the blood
glucose regulatory system as examples, my work looked at how we can
assess the effects of those uncertainties on the model output and what
this can tell us about the behaviour of the system.
The analysis of multi-scale models was addressed in my work using group-based sensitivity analysis which enables the identification of the most important sub-processes in the model. Together these methods provided a new methodology for sensitivity analysis in multi-scale systems biology modelling. I applied the methodology to a composite model of blood glucose homeostasis that combines models of processes at the sub-cellular, cellular and organ level to describe the physiological system. The results of the analysis suggest three main points about the system: the mobilisation of calcium by glucagon plays a minor role in the regulation of glycogen metabolism; auto-regulation of hepatic glucose production by glucose is important in regulating blood glucose levels; time-delays between changes in blood glucose levels, the release of insulin by the pancreas and the effect of the hormone on hepatic glucose production are important in the possible onset of ultradian glucose oscillations. These results suggest possible directions for further study into the regulation of blood glucose.
Page last modified on 21 aug 10 15:52