Prof. Adelle Coster (UNSW)

Abstract

Insulin has profound effects on cell metabolism, growth, proliferation and anti-apoptosis in mammalian cells. Dysregulation of the insulin signalling pathway is linked to the development of Type 2 diabetes, cardio-vascular disease, and cancer.

In general, measurements of living cells come from an external perspective – the key players may be known, but the details of their interactions are less well understood. The activation of the components in the insulin signalling pathway is controlled by not only biochemical phosphorylation but also by the physical location of the molecule, which may be translocated in response to upstream signals.

What can be inferred about this complex system, when the data is sparse and only subsets of states can be observed? Here we explore a mathematical model of a key component in the insulin signalling pathway of mammalian cells, Akt, and in doing so, identify the constraints on the timing of the upstream processes. The investigation also shows that the dominant processes regulating the appearance of Akt at the plasma membrane differ with insulin level.

The timing of Akt translocation and phosphorylation has ramifications for components downstream in the signalling pathway. Preliminary investigations of signalling delays are also explored for glucose transporter proteins in the signalling network.

About the speaker

Prof. Adelle Coster is an applied mathematician and head of the School of Mathematics and Statistics at the University of New South Wales. She uses dynamical systems analyses, stochastic modelling and queueing theory, amongst other techniques to answer questions arising from fields other than mathematics, particularly in biomedicine and biology. The investigations in which she currently involved range from understanding the dynamics of fundamental protein-protein interactions, cellular processes, the geometrical morphological features of microfossils, to the interactions in systems at larger scales involving human subjects. Projects include the modelling of

• cellular glucose transport in response to insulin and the deleterious effects insulin resistance and diabetes;
• the dynamics of electrically excitable cells such as peripheral nerves and the cardiac pacemaker; and
• starch grains within edible plants, allowing the identification of both contemporary grains and those found on ancient tools

Website: https://research.unsw.edu.au/people/professor-adelle-coster