PhD position: Dissecting early hypothalamus development through modelling and experiment

About the Project

This exciting interdisciplinary project brings together expertise in mathematical biology (Alexander Fletcher) and developmental neurobiology (Marysia Placzek) in the Neuroscience Institute at the University of Sheffield.

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.

How to apply

Please see this link for information on how to apply: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying. Please include the name of the first supervisor and the title of the PhD project within your application. Please state Division of Neuroscience as the division of your project, regardless of where your supervisor sits.

Interviews will be held late November/early December. Students must be able to start in February 2024.

Applications are open to home students only. We would expect applicants to have an excellent undergraduate degree in a relevant discipline. We would also expect applicants to have completed or be undertaking a relevant master’s degree to a similar very high standard (or have equivalent research experience).

For informal enquiries, please email Alexander Fletcher (a.g.fletcher@sheffield.ac.uk).

Funding Notes

References