Understanding the importance of location within the tumour-bone microenvironment

The majority of cancer deaths are due to metastasis, with bone being a major metastatic site for many common cancers. As such, modelling the complex cellular interactions within this specialised environment is essential for the development of new therapies. These interactions are key to driving many of the key features, including tumour growth and survival, dormancy, bone disease and drug resistance, and underpin the inevitably fatal outcome once tumours spread to bone. There is increasing evidence to support the importance of cellular location within the bone microenvironment. This project brings together the unique expertise of Profs Edwards and Walsh in bone oncology and engineering/microfluidics. Using state-of-the-art microfluidic devices(3-5), this project will study the interactions between tumour cells and cells of the bone microenvironment. Microfluidic devices will facilitate the study of the effect of the bone microenvironment on metastasis, enabling the investigation of cancer cell heterogeneity and the culture of multiple cell types. This project will provide a unique multidisciplinary opportunity, working within the research fields of tumour biology and engineering. State-of-the-art approaches will be used, including advanced cell culture systems, microfluidic devices, RNA-Sequencing, CRISPR/Cas9-mediated gene editing. This studentship will provide extensive opportunities for skill acquisition by the student. The goal of the project is to use state-of-the-art bioengineering approaches to interrogate the tumour-bone microenvironment and identify new therapeutic targets for the treatment of currently fatal skeletal malignancies such as multiple myeloma and prostate cancer bone metastases. As such, the project will address the following MRC strategic skill priorities. Quantitative skills: The student will undertake extensive training on analysis of next generation sequencing data as well as data analysis and statistical training. Interdisciplinary skills: The student will receive training in state-of-the-art techniques in bone oncology and bioengineering, including incorporating patient samples and therefore resulting in an interdisciplinary approach bridging oncology, bioengineering and the clinic. Whole organism physiology: The student will utilise in vivo models of bone oncology, facilitating a comprehensive study of the tumour-bone microenvironment.