Engineering the prostate tumour microenvironment in organ-on-a-chip systems

Overview

Prostate cancer remains one of the leading causes of global death. The tumour microenvironment (TME) including blood vessels, immune cells, fibroblasts, and the extracellular matrix (ECM) possesses disease-specific biophysical and biological factors that are difficult to recapitulate using conventional in vitro cell culture models.

The absence of these factors, however, causes cells to display abnormal morphologies, polarisation, proliferation, and drug responses, thereby limiting the ability to translate research findings from traditional cell culture into clinical practice.

Recent advances in organ-on-a-chip technology enable the development of microphysiological systems which provide unprecedented mimicry of the TME and facilitate mechanistic studies that may improve our understanding of prostate cancer pathogenesis and drug response. Organ-on-a-chip devices are microfabricated cell culture vessels that combine the advantages of microfluidic and 3D cell culture technology to mimic the complexity and characteristics of native organs.

Leveraging this technology, this project aims to develop advanced microfluidic tumour-on-a-chip models incorporating perfusable microvasculature, immune cells, prostate cancer spheroids, and cancer-associated fibroblasts to create biomimetic and highly predictive in vitro disease models. To engineer the TME, all cell types will be fluorescently tagged, embedded in biomimetic hydrogel extracellular matrices, and cultured in commercially available microfluidic chips.

Cellular self-organisation of the TME and the functional maturation of intratumoral microvascular networks in the matrix compartment will be characterised.

Aims:

1. Optimise hydrogel ECM properties to engineer vascularised TMEs in microphysiological chip systems.
2. Characterise the dynamic response of the TME to the growing cancer spheroids using immunofluorescence and live cell imaging techniques.
3. Characterise the response of the TME to anticancer drug treatment.

Research activities

This project is highly interdisciplinary and designed to expose the prospective student to a wide array of experimental techniques. It will facilitate the development of skills and experimental proficiency in the areas of cancer research, 3D cell culture, cell biology, and biomaterials.

You will develop expertise and technical skills in:

• traditional and 3D cell culture
• use of hydrogel biomaterials as extracellular matrix mimics
• microfluidic cell culture
• live cell fluorescence microscopy
• bioassays (cell viability, metabolic activity, proliferation)
• immunofluorescence staining
• data analysis and presentation.

Outcomes

The project will deliver a state-of-the-art tissue-engineered TME-chip model enabling detailed mechanistic studies to significantly improve the understanding of the prostate cancer TME and support the development of novel therapeutic strategies.

Skills and experience

You should have a keen interest in cancer research and demonstrate a high level of organisation, attention to detail and ability to work in a team environment. Basic skills in cell culture and general PC2 laboratory techniques are desired.

Scholarships

You may be eligible to apply for a research scholarship.

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Keywords

• prostate cancer
• organ-on-a-chip
• tumour microenvironment
• tissue engineering
• microfluidics
• hydrogel extracellular matrix

Contact

Contact the supervisor for more information.