PhD Studentship: Mathematical Modelling of Cytoneme-based Biochemical Signalling

Project Title: Mathematical modelling of cytoneme-based biochemical signalling

Project Description:

Cytonemes are cellular protrusions that enable long distance communication between cells. They are implicated in establishing the morphogenetic gradients associated with pattern formation during development [Brunt et al., 2021], in the growth of gastric tumours [Routledge et al., 2022], and have recently been suggested to promote synapse formation in neurons. Despite their pivotal role in such important physiological processes, cytonemes have received relatively little mathematical treatment. In this project, we will use a combination of mathematical modelling and data analysis techniques to determine the signalling properties of cytonemes that are relevant for tissue patterning and tumour growth.

The mathematical models developed in the project will be based on a PDE-formulation and will build on recent work describing tissue patterning in growing domains [Wedgwood & Ashwin, 2022]. The models will describe the dynamics of two processes. The first will be the growth and retraction of the cytonemes and hence the dynamics of long-range signalling. The second will be the mechanical forces underlying the growth of the biological tissue. These mechanical forces are generated by the movement of cells which, in turn, is dependent on the degree of signalling across the tissue. As such, the tissue growth dynamics are tightly coupled to the cytoneme dynamics. Data to parametrise the models of both processes will be available through our experimental partner Dr Steffen Scholpp.

Using our developed model, we will study three related projects. Specifically, we will investigate:

1. How cytoneme signalling contributes to the acquisition of robust boundaries between forebrain, midbrain, and hindbrain regions during gastrulation. We will compare results with our previously developed model [Wedgwood & Ashwin, 2022], in which transport occurs by linear diffusion, to assess what advantages a cytoneme-signalling system might possess over purely diffusive systems.
2. How gastric tumour growth is regulated by cytoneme signalling. We will derive quantitative links between parameters associated with cytoneme dynamics and those associated with tumour spheroid growth. Using these, we explore different drug-based strategies for limiting or reversing tumour growth by manipulating cytoneme dynamics.
3. How cytonemes underpin synapse formation. We will append our model with additional processes to describe calcium signalling events that are associated with synapse formation. Using this appended model, we will identify cytoneme parameters that lead to successful synapse formation and further explore how neuronal networks develop in response to cytoneme signalling.

Entry requirements

Applicants for this studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of mathematics, physics or natural sciences.

If English is not your first language you will need to meet the required level (Profile A/B/C)  as per our guidance at:   https://www.exeter.ac.uk/study/englishlanguagerequirements/?utm_source=jobsacuk&utm_medium=affiliate&utm_campaign=uoe-studentships-pgr-4743-2023

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