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Development of oblique plane microscopy to accelerate our ability to understand and target complexity and heterogeneity in cancer

Project Description

Increasingly, the use of conventional 2-D cell cultures (typically monolayers of cells on glass or plastic substrates) are being found to be inadequate as models of biological systems for the purposes of fundamental biology research and drug discovery. This project aims to explore the trade-off between complexity of 3D cancer models and power of assays (in terms of single cell resolution and throughput) by developing and applying modular open-source automated instrumentation optimised for 3D imaging of complex cell cultures with a range of optical properties. This automated 3D imaging instrumentation is intended to provide quantitative single cell-resolved readouts in fixed and live cell cancer models, particularly tumour spheroids and patient-derived organoids (PDO), where signalling processes are expected to be much closer to the in vivo context than for conventional 2-D cell cultures. The project would be undertaken as part of a CRUK-funded Accelerator project, which is a collaboration with colleagues in biology, chemistry and medicine at Imperial, the Francis Crick Institute, the Institute of Cancer Research, the University of Edinburgh and the IRB Barcelona.

This project will develop, apply and utilise a new state-of-the-art automated light-sheet multiwell-plate oblique plane microscope (OPM) at the Institute of Cancer Research to provide 3D imaging of 3D cell cultures and PDOs in 96 and 384-well formats. The PhD student will become expert in the use of the instrument, develop new image analysis pipelines and interpret these results in the context of the biology. The system will be used to provide quantitative single cell-resolved readouts and responses in fixed and live cell cancer models across a wide-range of conditions and provide functionality beyond the commercial state-of-the-art, e.g. providing faster 3D imaging of cell morphology, dynamics and migration in multiwell plate arrays. The project will enable studies of which cells within a heterogeneous cancer population are effectively killed by chemotherapy and which of the persisting cells are responsible for disease recurrence. It will also be used to explore the role of the tumour microenvironment for quiescent chemotherapy-resistant tumour cell sub-populations.

Please contact Dr Chris Dunsby or Dr Chris Bakal for more information.

Funding Notes

This is a 4-year CRUK-funded studentship (open to UK and EU candidates). The ideal candidate would have a keen interest in the development and application of new tools and methodologies to study cancer biology and for drug discovery, and would welcome the multidisciplinary nature of the project. In particular they should have a strong physical- or computer-sciences background. A high level of computer literacy, including experience of computer programming is essential. The project is based at the ICR and will be co-supervised by Chris Bakal at the ICR and Chris Dunsby in the Photonics Group at Imperial.

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