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Mathematical Modelling of Cancer-Cell Transmigration Through Blood Vessels


School of Mathematics

Thursday, December 10, 2020 Competition Funded PhD Project (Students Worldwide)

About the Project

Cancer rarely kills through the primary tumour in which cancer arises, e.g. the prostate in prostate cancer. Instead, cancer cells can travel through the vasculature and colonialize distant organs – a process termed metastasis. A critical step of metastasis is the crossing of the cancer cells through the endothelium – the layer of endothelial cells that line the inside of blood vessels.

This endothelium is a highly dynamical structure that regulates transport of nutrients and oxygen to the tissue in healthy humans. It also allows for formation of gaps that allow immune cells to enter infected tissues. However, precisely these gaps are exploited by the cancer cells to invade the tissues. Recent research has shown that the regulation of these gaps is a complicated project, involving endothelial-cell internal signalling, the mechanics of the endothelium, and the mechano-chemical interactions of the endothelium with the extravasating cells.
Here, we will construct mechanochemical models of cancer-endothelial interactions. We will use this model to probe the major contributing factors to the process of transmigration. The model predictions will be validated through collaborations with leading experimental groups that can measure the forces during this process, such as the groups of our collaborators Prof. Emad Moeendarbary from UCL and Prof. Anne Ridley from Bristol. We will also collaborate with the modelling groups of Prof. Manu Garcia Aznar and Prof. Maria Jose Gomez-Benito from the University of Zaragoza. Together, we will uncover the bi-directional molecular signalling cascades between cancer and endothelium, and how this signalling contributes to altered cell mechanics and gap opening.

Methods: The project may involve several of the following methods: Discrete or continuum mechanics, Monte Carlo simulations, multiscale modelling, data analysis


Funding Notes

Excellent students with a first class MSci/MSc or equivalent qualification in mathematics, physics, engineering or related sciences are encouraged to send informal inquiries to . Funding is available for UK students and potentially for international students. Candidates with external scholarships are welcome to apply if they have excellent qualifications.

Official applications have to be submitted through this webpage, selecting a PhD in Applied Mathematics
View Website

References

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006395

https://www.sciencedirect.com/science/article/pii/S0013794419302255

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