Reprogramming of life and death pathways in cancer through unfavourable interactions with healthy cells

Cells utilise intracellular molecular networks to perform all their essential functions. These functions include the processing of food and generation of energy to live, grow and divide. Such networks also control cell death, which may, for example, be initiated, in response to limited oxygen or food, or to cell damage. Cancer cells are characterised by their advanced capabilities to survive and proliferate in adverse cellular environments, giving them growth advantages compared to healthy tissue. They are also characterised by increased resistance to cell death. Therefore, a lot of research has focused on how the cellular networks within cancer cells is reprogrammed.
Traditionally most of the experimental and modelling research focused on the analysis of the networks within individual cancer cells, treating them as isolated closed systems. However, we now know that cancer cells will behave very differently in different cellular environments. These different environments are characterised by the presence of healthy cells, including immune cells or stromal cells, but also by physical variables including mechanical resistance of the tissue, or the local oxygen concentrations. New experimental evidence shows that some healthy cells can produce nutrients that are taken up by cancer cells. Therefore, the molecular crosstalk with healthy cells can help to fuel the growth of these cancer cells.

In this project, you will develop mathematical models to uncover the crosstalk of cancer and healthy cells. The models will be initially set up with experimental data from the lab of Dr Dan Tennant (https://www.tennantlab.uk/). Then, you will make new predictions to identify key molecules that facilitate the crosstalk of these cells. This work may therefore identify new drug targets that can inhibit the crosstalk and therefore limit cancer growth, or, in the best case, reprogram cancer cells towards cell death. By working closely with the experimentalists, you will ensure the developed models are realistic and can be validated by new experiments.
This project is part of a larger-scale initiative of collaborative projects between the University of Birmingham’s School of Mathematics and the Institute of Metabolism and Systems Research that also involves Dr David Tourigny (Columbia University), Dr Vijay Rajagopal (University of Melbourne) and Dr Michael Mak (Yale University).

Methods: The project may involve several of the following methods: differential equations, metabolic flux analysis, optimisation, machine learning, agent based models, stochastic processes, image analysis, statistical analysis. Which methods are developed for this project will depend on the skills and interests of the successful candidate. Training on methods the candidate wishes to learn will be provided. The essential requirement are strong academic performance (e.g. evidenced through an excellent 1st class degree in Mathematics, Theoretical Physics, Computational Biology or related subjects), and motivation to work in an interdisciplinary environment.