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Combining mechanical modelling with image segmentation analysis to understand breast organoid formation


Project Description

Note - Applicants for these awards must have a home or work address in the East area of Wales at the time of their application for funding and enrolment.

Organoids are three-dimensional (3D) stem cell cultures that can self-organise into ‘mini-organs.’ They facilitate the study of tumour pathology to enable cancer drug discovery. Organoids are closer to in vivo tumours than more conventional 2D cell line cultures and can provide more relevant pharmacological responses to drugs and antibodies.

By using organoids in drug discovery screening assays, scientists can identify active compounds for further progression earlier in the drug discovery process and weed out less attractive compounds before incurring higher downstream costs.

Recently, Cellesce has developed imaging techniques that allow them to extract over 900 morphometric parameters of an organoid and, further, measure the influence of drug effects on these parameters. However, although effect identification and principle component analysis are good methods to begin with, as they highlight important correlations, they do not shed light on the mechanistic coupling between these components.
Project aims

This project aims to use an advanced cell-based simulation software (CHASTE) to derive rules that will allow individual cells to reproduce and develop into organoid morphologies. Further, by linking the mechanistic properties to hormone signalling pathways we will be able to construct a fully 3D ’in silico’ therapeutic testing bed.

Such a computational model provides a number of benefits, such as speeding up experimentation. Equally, a single computational model can be trivially parallelised allowing us to test new breast cancer therapies on their own, or in specific combinations allowing us to design optimal dosing strategies.

Critically, due to the use of donated tumour tissue, it is potentially possible to individualise the simulation results based on parameters extracted from a patient’s specific tissue, thus, providing personalised medical strategies.

Funding Notes

Applicants for these awards must have a home or work address in the East area of Wales at the time of their application for funding and enrolment. East Wales region is comprised of seven local authorities: Cardiff, Flintshire, Monmouthshire, Newport, Powys, Vale of Glamorgan and Wrexham.

Applicants must:
-have the right to work in the UK on completion of the scholarship
-be classified as a ‘home’ or ‘EU’ student
-satisfy the respective admissions criteria

References

Applicants should submit an application for postgraduate study via the Cardiff University Online Application Service.
http://www.cardiff.ac.uk/study/postgraduate/applying/how-to-apply/online-application-service/mathematics-research
Applicants should select Doctor of Philosophy (Mathematics), with a start date of July 2019.

In the research proposal section of your application, please specify the project title and supervisors of this project. In the funding section, please select "I will be applying for a scholarship / grant" and specify that you are applying for advertised funding from KESS2.

Shortlisted candidates will be invited to attend an interview after the closing date

How good is research at Cardiff University in Mathematical Sciences?

FTE Category A staff submitted: 24.05

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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