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  Exploring the effect of hypoxia upon glioblastoma progression and response to treatments using a dynamic 3D iPSC-brain organoid


   Cardiff School of Pharmacy and Pharmaceutical Sciences

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  Dr Catia Neto, Prof M Gumbleton  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Background

Glioblastoma (GBM) is the most aggressive brain tumour, displaying considerable resistance to drug-/radiation-therapies. Tumour recurrence after surgery is common with patient survival approximately 5% at 5 years post-diagnosis. The Tumour microenvironment (TME) has profound effects upon tumour aggressiveness and the treatment response. GBM comprises a substantial proportion of non-cancerous brain-resident cells and infiltrating immune cells from the blood. Cancer cell-TME interactions are complex and can modulate the response to therapies.

Hypoxia is a hallmark of GBM which is associated with multiple aspects of tumour pathogenesis and chemotherapies and radiotherapies response. For example, it is known that hypoxia induces resistance to conventional cancer therapies and inhibits antitumour immune response.

Due to the lack of clinically and biologically relevant models to study brain tumours, our group dedicated the last years developing a patient-specific multilineage iPSC-brain organoid model. The iPSC-brain organoid is a dynamic tissue structure, composed by astrocytes, neurons, and infiltrated by microglia and/or macrophages. The isogeneic tumour cells are then incorporated into the model to study tumour biology, tumour-non-tumour cell interactions and drug screening.

Project

The aim of this project is to evaluate the effect of controlled environmental conditions (hypoxia) on glioma tumours, including response to new therapies, using an iPSC-brain organoid. By working on this project, the PhD candidate will learn a range of cutting-edge in-vitro model techniques (2D and 3D), including cell culture of induced pluripotent stem cells (iPSC), immune and tumoral cells. The candidate will also learn high resolution microscopy techniques to investigate cell‐cell interactions and drug effects, analysis of cell viability, clonogenic survival, protein and mRNA expression, and immunofluorescence imaging. Such knowledge will be extremely valuable for those wishing to pursue a career in academia or with pharmaceutical/biotechnology companies.

Biological Sciences (4) Medicine (26)

Funding Notes

The PhD opportunity is a full time 3 year programme working with academic researchers (Schools of Pharmacy and Pharmaceutical Sciences and Biosciences, Cardiff University).
Currently the opening is only available to those candidates able to evidence sponsorship for their PhD tuition fees and subsistence costs (3 years of study).
Applicants must have obtained a First or Upper Second Class UK Honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of science.
For further details please contact: Dr Catia Neto ([Email Address Removed])

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