Creation and characterisation of tumour organoids for better understanding of canine cancer microenvironment and personalised approach to patients’ cancer care at University of Edinburgh on FindAPhD.com

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Mr M Parys, Prof T Hupp No more applications being accepted Funded PhD Project (Students Worldwide)

About the Project

Cancer is one of the most common chronic diseases in dogs, with a significant welfare burden for both animals as well as their caretakers. Novel approaches to predict responses to treatment in an individual in a minimally invasive way are urgently needed. Until recently most studies have been performed in 2D cultures, not considering the tumour microenvironment, thus making the prediction less accurate and frequently failing. 2D cultures are also difficult to establish and sustain. Recently 3D organoid culture has been porposed as a novel method to be used in prediction of responses to various types of treatments (chemotherapy, small molecule inhibitors or immunotherapy). In this type of culture, the tumour is being dissociated and cells are embedded in 3D matrix, overlaid with cell culture medium containing a variety of growth supplements. Importantly the microenvironment structure is largely sustained in the early passages and resembles the one from the original tumour. The primary aim of this project is to establish protocols for organoid cultures of various types of canine cancers. Subsequently the organoids will be phenotypically characterised and compared to the original tumour bulk. Multicolour flow cytometry will be utilised to investigate changes in tumour immune infiltrates. Subsequently, selected tumour organoids will be used for testing of various chemotherapeutics and immunotherapeutics to investigate if they can be used as predictor of response to this type of therapy.

Other projects available:
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 10th January 2020 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships

Funding Notes

3.5 year PhD
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.

All applicants should also apply through the University's on-line application system for September 2020 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=826

References

- Dijkstra, K. K., C. M. Cattaneo, F. Weeber, M. Chalabi, J. van de Haar, L. F. Fanchi, M. Slagter, D. L. van der Velden, S. Kaing, S. Kelderman, N. van Rooij, M. E. van Leerdam, A. Depla, E. F. Smit, K. J. Hartemink, R. de Groot, M. C. Wolkers, N. Sachs, P. Snaebjornsson, K. Monkhorst, J. Haanen, H. Clevers, T. N. Schumacher and E. E. Voest (2018). "Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids." Cell 174(6): 1586-1598.e1512.
- Pauli, C., B. D. Hopkins, D. Prandi, R. Shaw, T. Fedrizzi, A. Sboner, V. Sailer, M. Augello, L. Puca, R. Rosati, T. J. McNary, Y. Churakova, C. Cheung, J. Triscott, D. Pisapia, R. Rao, J. M. Mosquera, B. Robinson, B. M. Faltas, B. E. Emerling, V. K. Gadi, B. Bernard, O. Elemento, H. Beltran, F. Demichelis, C. J. Kemp, C. Grandori, L. C. Cantley and M. A. Rubin (2017). "Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine." Cancer Discovery 7(5): 462-477.
- Jenkins, R. W., A. R. Aref, P. H. Lizotte, E. Ivanova, S. Stinson, C. W. Zhou, M. Bowden, J. Deng, H. Liu, D. Miao, M. X. He, W. Walker, G. Zhang, T. Tian, C. Cheng, Z. Wei, S. Palakurthi, M. Bittinger, H. Vitzthum, J. W. Kim, A. Merlino, M. Quinn, C. Venkataramani, J. A. Kaplan, A. Portell, P. C. Gokhale, B. Phillips, A. Smart, A. Rotem, R. E. Jones, L. Keogh, M. Anguiano, L. Stapleton, Z. Jia, M. Barzily-Rokni, I. Cañadas, T. C. Thai, M. R. Hammond, R. Vlahos, E. S. Wang, H. Zhang, S. Li, G. J. Hanna, W. Huang, M. P. Hoang, A. Piris, J.-P. Eliane, A. O. Stemmer-Rachamimov, L. Cameron, M.-J. Su, P. Shah, B. Izar, M. Thakuria, N. R. LeBoeuf, G. Rabinowits, V. Gunda, S. Parangi, J. M. Cleary, B. C. Miller, S. Kitajima, R. Thummalapalli, B. Miao, T. U. Barbie, V. Sivathanu, J. Wong, W. G. Richards, R. Bueno, C. H. Yoon, J. Miret, M. Herlyn, L. A. Garraway, E. M. Van Allen, G. J. Freeman, P. T. Kirschmeier, J. H. Lorch, P. A. Ott, F. S. Hodi, K. T. Flaherty, R. D. Kamm, G. M. Boland, K.-K. Wong, D. Dornan, C. P. Paweletz and D. A. Barbie (2018). "Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids." Cancer Discovery 8(2): 196-215.

Where will I study?

University of Edinburgh

One of the world''s top universities, consistently ranked in the world top 50 and placed 20th in the QS World University Rankings 2020. We provide a stimulating working, learning and teaching environment with access to excellent facilities and attract the world''s best, from Nobel Prize winning laureates to future explorers, pioneers and inventors.

Creation and characterisation of tumour organoids for better understanding of canine cancer microenvironment and personalised approach to patients’ cancer care

University of Edinburgh College of Medicine and Veterinary Medicine