I am willing to supervise PhD projects in mathematical biology. Please email me if you are interested in the funded project(s) listed below, or in some other topic related to my research; you can find a list of past PhD projects here. To apply formally for funding and a place, you must complete an online application form.
This exciting interdisciplinary project brings together expertise in biomedical sciences and mathematical biology. The project will be co-supervised by Prof. Alexander Fletcher (School of Mathematical and Physical Sciences, University of Sheffield) and Prof. William Brackenbury (Department of Biology, University of York).
Pathophysiological adaptations within the tumour microenvironment, including plasticity of cell/tissue-level metabolic and ionic gradients, can drive breast cancer progression and invasiveness. These gradients, together with cellular responses constitute a bioelectrical dynamics that is poorly understood yet presents novel therapeutic opportunities. To understand the bioelectrical dynamics of breast cancer, we must integrate physiological parameters across scales. For example, tissue-scale pH and oxygen gradients can influence cellular membrane potential, redox and carbon metabolism, cell motility and mechanics, resulting in tumour re-modelling and linking to invasiveness. Addressing this requires a novel approach combining multiscale computational modelling and experiments.
In this project, you will develop a computational model of the spatial organisation of breast cancer cells that accounts for cellular metabolism, membrane potential and feedback coupling with tissue-level metabolic and ionic gradients. To inform this model, you will experimentally measure key physiological and metabolic parameters in breast cancer cells and tissue. Using this model and further experiments, you will predict and test how bioelectrical or mechanical stimulation affects the dynamic bioelectric state of breast cancer cell populations, with a view to bioelectrically suppressing tumour invasiveness.
The project will provide a novel contribution to understanding/controlling the breast cancer microenvironment, helping to address the clinical need for novel therapies to suppress breast cancer invasion in the window between diagnosis and surgical resection, thus improving prognosis. There is an urgent need for new therapies to suppress cellular invasion from the primary tumour, reducing metastasis risk: early-stage breast cancer patients have a high survival rate, assuming no locoregional or systemic disease, yet metastatic breast cancer remains incurable. We envisage that this partnership will enable us to achieve the goal of rationalising bioelectrical phenomena within the tumour microenvironment, with a view to later extending these models to mouse mammary xenograft tumour tissue slices and translating them towards the clinic, leveraging future benefit to patients.
This project would be suitable for a mathematics or physics student with knowledge of differential equations and scientific computing who is keen to apply their expertise to cancer biology, or a biology student with knowledge of cell biology or cancer who is keen to develop mathematical and quantitative skills. The supervisory team will hold regular meetings with the student to monitor their progress. The student will benefit from the complementary expertise of the two supervisors by receiving in-depth training in computational (agent-based and multiscale) and experimental (molecular biochemistry, biophysics, cancer biology, electrophysiology) techniques, tailored to their needs.
A competitively funded studentship is available via the MRC DiMeN Doctoral Training Partnership. Please see this link for information on how to apply. The deadline for applications will be Friday 15th December at 5pm (UK time)..
Please contact me (a.g.fletcher@sheffield.ac.uk) for more information.