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 developmental neurobiology and mathematical biology in the Neuroscience Institute at the University of Sheffield. The project will be co-supervised by me and my collaborator Prof. Marysia Placzek from the School of Biosciences.
The hypothalamus is a small region of the brain that is critical to life, controlling growth, metabolism and reproduction, yet we understand little about its development. This project aims to understand how key chemicals, termed morphogens, interact to direct each cell to adopt the right behaviour at the right time within the developing hypothalamus. This could eventually help us to build the hypothalamus in a dish, which would enable us to make personalised cells and restore damaged brain cells. Given the complexity of these processes, mathematical modelling plays an increasingly useful role in aiding our understanding, while experiments allow us to constrain and test models.
In this project, we will combine mathematical modelling with experiments in the early chick hypothalamus, where we can manipulate key parameters and explore how this affects the shape and structure of the resulting tissue. First, we will construct a dynamical model of coupled differential equations describing the activity of key hypothalamus morphogens, identifying best-fit network topologies and parameters from existing wild-type data using Bayesian and machine learning approaches. This will then be integrated into a multiscale computational model of cell movement and proliferation, allowing us to couple patterning events to tissue morphogenesis. Finally, we will test the model by simulating the introduction of coated beads to perturb key morphogens, and comparing the predicted effect on tissue growth, shape and morphogen regionalization against that obtained experimentally in vivo and ex vivo. Models will be tested using methods such as sparse regression and physics-informed neural networks to denoise data and approximate spatial gradients.
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 biology, or a biology student with knowledge of cell and developmental biology or neuroscience who is keen to develop mathematical and quantitative skills. The student will be provided with a thorough interdisciplinary training in mathematical modelling, quantitative analysis and laboratory skills.
A competitively funded studentship is available via the Neuroscience Institute. Please see this link for information on how to apply. Please include the name of the first supervisor (me) and the title of the PhD project (see above) within your application. Interviews will be held late November/early December. Students must be able to start in February 2024. Applications are open to home students only. The deadline for applications will be 10th November 2023.
Please contact me (a.g.fletcher@sheffield.ac.uk) for more information.
The proper function of our gut is controlled, in an involuntary fashion, by a complex network of nerves called the enteric nervous system (ENS), also known as the ‘second brain’. The ENS is produced in embryos by specialised cell populations known as ENS progenitors. A number of developmental defects (such as Hirschsprung disease) and adult conditions (e.g. Parkinson’s disease) are associated with defective ENS development and subsequent dysfunction. It is therefore essential to understand the mechanisms guiding the transition of ENS progenitors toward their derivatives. Notch signalling is a key pathway controlling this process and mutations in its components lead to Hirschsprung disease.
In this project, we will employ a systems biology approach, iterating between a human pluripotent stem cell (hPSC)-based in vitro model of ENS development and an in silico computational model, to determine the role of Notch in ENS progenitor biology. This project will be co-supervised by me and my collaborator Dr Anestis Tsakiridis from the School of Biosciences.
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 biology, or a biology student with knowledge of cell and developmental biology or neuroscience who is keen to develop mathematical and quantitative skills. The student will be provided with a thorough interdisciplinary training in mathematical modelling, quantitative analysis and laboratory skills.
A competitively funded studentship is available via the White Rose Mechanistic Biology DTP. Candidates must apply to the DTP centrally (Leeds) using a single online “expression of interest” form (CV information will be captured on the form). The deadline for applications will be 7th January 2024.
Please contact me (a.g.fletcher@sheffield.ac.uk) for more information.