Understanding the importance of location within the tumour-bone microenvironment
- Project No: NDORMS-2021/10
- Intake: 2021
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 (1, 2). For example, dormancy is a key mechanism controlling tumour progression within bone that is dependent upon interactions between tumour cells and the endosteal bone surface (the ‘dormant niche’).
This project brings together the unique expertise of Profs Edwards and Walsh in bone oncology and engineering/microfluidics(1-5). Using state-of-the-art microfluidic devices(3-5), this project will study the interactions between tumour cells and cells of the bone microenvironment, including osteo-blasts/-clasts, bone marrow stromal cells (BMSCs), adipocytes, plus immune and endothelial cells, focusing on proximity and spatial control. Microfluidic devices will facilitate the culture of multiple cell types, and the investigation of morphogen gradients within the tumour-bone microenvironment, a key developmental concept whose application to the tumour-bone environment advances our understanding of spatial control of tumour growth and survival. This project will interrogate the spatial relationship between tumour cells and bone cells, focusing on BMP family morphogen gradients.
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-Seq, CRISPR/Cas9-mediated gene editing.
THE RESEARCH GROUP
The student will be jointly supervised by Prof. Claire Edwards (Nuffield Dept. of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS)/ Nuffield Dept. of Surgical Sciences (NDS)), Prof. James Edwards (NDORMS), Prof. Edmond Walsh (Dept. of Engineering Science) and Dr. Srinivasa Rao (NDS). They will be based within both the Edwards group at the Botnar Research Centre, and the Walsh group in the Dept. of Engineering Science. For informal enquiries, please contact Claire Edwards.
The student will work within NDORMS, based at the Botnar Research Centre, and the Dept. of Engineering Science, providing a strong environment for training across the disciplines of engineering and medical sciences. The Botnar Research Centre plays host to the University of Oxford's Institute of Musculoskeletal Sciences, which enables and encourages research and education into the causes of musculoskeletal disease and their treatment. A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology, data analysis and the microbiome. Students will also be required to attend regular seminars within the Department and those relevant in the wider University.
Students will be expected to present data regularly in Departmental seminars, the Edwards’ and Walsh lab group meetings and to attend external conferences to present their research globally, with limited financial support from the Department. Students will have access to various courses run by the Medical Sciences Division Skills Training and other Departments.
1. Gooding S, Olechnowicz SWZ, Morris EV, Armitage AE, Arezes J, Frost J, et al. Transcriptomic profiling of the myeloma bone-lining niche reveals BMP signalling inhibition to improve bone disease. Nature communications. 2019;10(1):4533.
2. Rao SR, Howarth A, Kratschmer P, Snaith AE, Yapp C, Ebner D, et al. Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis. Frontiers in oncology. 2020;10:292.
3. Soitu C, Feuerborn A, Deroy C, Castrejon-Pita AA, Cook PR, Walsh EJ. Raising fluid walls around living cells. Sci Adv. 2019;5(6):eaav8002.
4. Soitu C, Feuerborn A, Tan AN, Walker H, Walsh PA, Castrejon-Pita AA, et al. Microfluidic chambers using fluid walls for cell biology. Proc Natl Acad Sci U S A. 2018;115(26):E5926-E33.
5. Walsh EJ, Feuerborn A, Wheeler JHR, Tan AN, Durham WM, Foster KR, et al. Microfluidics with fluid walls. Nature communications. 2017;8(1):816.
HOW TO APPLY
The Department accepts applications throughout the year but it is recommended that, in the first instance, you contact the relevant supervisor(s) or the Graduate Studies Officer, Sam Burnell (Samuel.firstname.lastname@example.org), who will be able to advise you of the essential requirements. Interested applicants should have, or expect to obtain, a first or upper second-class BSc degree or equivalent in a relevant subject and will also need to provide evidence of English language competence (where applicable). The application guide and form is found online and the DPhil or MSc by research will commence in October 2021.
Applications should be made to one of the following programmes using the specified course code:
D.Phil in Musculoskeletal Sciences (course code: RD_ML2)
MSc by Research in Musculoskeletal Sciences (course code: RM_ML2)
For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford.