Dr Kyle Wedgwood

About me

I am an Associate Professor in the Department of Mathematics and Statistics, housed with the Living Systems Institute. I work primarily in the Faculty of Environment, Science and Economy, but work closely with the Faculty of Health and Life Science. In my research, I apply techniques from mathematical modelling (dynamical systems theory, bifurcation analysis) to understand how networks of cells come together to form biological networks that can perform functional tasks. I am particularly interested in spatio-temporal patterns of neural activity in the brain and their role in memory and spatial navigation, and the synchronisation of electrical activity amongst the insulin-secreting beta cells in the pancreas. 

Funding

I am generously supported by a UKRI Future Leaders Fellowship and am a co-investigator on the EPSRC Hub for Quantitative Modelling in Healthcare.

I have previously been supported by the Medical Reseach Council as a Skills Development Fellow and via an EPSRC New Horizons Grant.

I am happy to support applications for summer internships for undergraduate students to the Society for Endocrinology, British Society for Neuroendocrinology and the London Mathematical Society. I have previously supervised three such internships in the past.

Research team

Postdoctoral research fellows:

Melvyn Tyloo

PhD students:

Henry Kerr
Akshita Jindal
Victor Applebaum

Wolf Byttner

Alan Buchanan

Previous postdoctoral research fellows

Nicolás Verschueren van Rees

Previous PhD students

Bonnie Liefting

Prospective PhD students

Please get in touch if you wish to discuss developing a research proposal for PhD study. I am open to any project that invovles dynamical systems and biology, particularly if it involves diabetes, neuroscience or pattern formation.

Projects available for application:

Mathematical modelling of cytoneme-based biochemical signalling (deadline 10th January 2025 - apply here)

Supervisory team:          Dr Kyle Wedgwood (Department of Mathematics and Statistics)

                                        Prof Steffen Scholpp (Department of Biosciences)

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, some of which are shown in the figure below, will be available through our experimental partner Prof 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.

References:

Brunt, L., Greicius, G., Rogers, S., Evans, B. D., Virshup, D. M., Wedgwood, K. C. A., & Scholpp, S. (2021). Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling. Nature Communications, 12(1).

Routledge D., Rogers S., Ono Y., Brunt L., Meniel V., Tornillo G., Ashktorab H., Phesse T. J., & Scholpp, S. (2022). The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer. eLife, 11:e77376.

Wedgwood K. C. A & Ashwin P. (2022), Morphogen-directed cell fate boundaries: slow passage through bifurcation and the role of folded saddles. Journal of Theoretical Biology, 549:111220.

Project page

Further details of my research projects can be found here.