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Modelling of Epithelial-to-Mesenchymal Transition in Invading Cells

Objective

Cell migration is at the core of many biological processes in development and cancer progression. Epithelial-to-mesenchymal transition (EMT), i.e. the temporary and reversible switching between epithelial and mesenchymal phenotypes, plays a crucial role in increasing the motility and invasiveness of cells, representing a potential therapeutic target in many biomedical areas. With the surge of omics data, we are now more than ever able to characterise the phenotypic properties of cells and require theoretical frameworks which can effectively integrate such information to help us predict tissue-level behaviours for optimisation of therapeutic interventions.

My project is devoted to the development of such a theoretical framework, in which cell migration through the extracellular matrix (ECM) is mediated by the cell phenotypic state which may change guided by mechanistic rules for EMT, incorporating information on the cell phenotypic state coming from omics data.

I will focus on mathematical models comprising nonlocal partial differential equations of the evolutionary dynamics of space- and phenotype-structured cell populations. By representing cell phenotypes on a continuum, the models can capture intratumour heterogeneity and hybrid phenotypes, and may be directly linked with transcriptomic and proteomic data. This project will tackle the analytical and numerical challenges stemming from movement in physical space, modelling heterogeneous cell motion in the ECM, and complex phenotypic drifts, incorporating a description of core regulatory circuits for EMT, yet to be investigated in a unified framework. Moreover, we will address the inverse problem of employing transcriptomic data to infer the nonlinear impact of environmental factors on the core regulatory circuit mediating phenotypic changes, to this day an open problem.

The outcomes of the project will advance mathematical, biomedical and interdisciplinary research.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 260 347,92
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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