PhD: Through the Tumour Labyrinth: Developing a Mechanistic Understanding of Blood Flow and Oxygen Delivery in Tumour Vasculature

University of Edinburgh

Blood flow patterns in tumour vasculature are known to be highly irregular, with the distribution of red blood cells (or haematocrit) showing marked deviations from those observed in healthy tissue vasculature. These abnormalities present a challenge for drug delivery and have been linked to tumour hypoxia and enhanced tumour angiogenesis.

To date, many of the available computational models of tumour blood flow describe blood as a homogeneous fluid and employ phenomenological rules to determine haematocrit changes at vessel bifurcations. This is, in part, due to the computational challenges associated with simulating haematocrit changes in a mechanistic way, i.e. by explicitly describing the transport of red blood cells (RBC) in plasma. Unfortunately, such simplified approaches fail to capture the complex haemodynamics encountered in tumours.

Co-supervisors Bernabeu and Krüger have recently developed an extension to the blood flow simulation platform HemeLB that enables the simulation of blood flow as a suspension of RBCs. Co-supervisor Byrne and colleagues in Oxford and Barcelona have considerable experience of simulating blood flow and oxygen distributions in tumours and have recently developed a microfluidics assay that recapitulates RBC dynamics in tumour vascular networks. Both computer simulations and microfluidics experiments are informed by novel intravital microscopy data of mouse tumour xenographs generated by close collaborators.

In this project, we aim to integrate data from computer simulations, microfluidic platforms, and intravital microscopy in order to develop a mechanistic understanding of blood flow and oxygen delivery in tumour vasculature. This knowledge will allow us to formulate a theory of transport in the tumour vasculature that is suitable for evaluating vascular normalisation strategies.

Supervisors:

  • Dr Miguel O. Bernabeu, Centre for Medical Informatics, The University of Edinburgh.
  • Dr Timm Krüger, Department of Engineering, The University of Edinburgh.
  • Prof. David Robertson, Centre for Medical Informatics, The University of Edinburgh.

In collaboration with:

  • Prof. Helen Byrne, Mathematical Institute, University of Oxford.
  • Prof. Tomás Alarcón, Centre de Recerca Matemàtica, Barcelona, Spain.
  • Prof. Ruth Muschel, Department of Oncology, University of Oxford.

Requirements

A strong academic track record with a 2:1 or higher in a relevant undergraduate degree, or its equivalent if outside the UK. It is also desirable to have a strong performance in a relevant postgraduate degree. Proven experience in one or more of the following is desirable: mathematical modelling, computational fluid dynamics, image processing or one scientific programming language (e.g. C++, Python, Fortran). The successful candidate will work in a highly interdisciplinary environment and should be able to work independently and as part of a distributed international team.

Application procedure

Please provide a CV, a personal statement detailing your research interests and reasons for applying, degree certificate(s), marks for your degree(s) and 2 written academic references. All documents should be in electronic format and sent via e-mail to: S.Georges@ed.ac.uk

For further information about the project contact the primary supervisor: miguel.bernabeu@ed.ac.uk

The closing date for applications is: 15 October 2017

Interviews will be held during October 2017.

Funding Notes

This is a University of Edinburgh funded award and will provide an annual stipend for three years of £14,553 per year (subject to confirmation), plus University fees for UK/EU students. Any eligible non-EU candidates must fund the remainder of the overseas tuition fee.

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Type / Role:

PhD

Location(s):

Scotland