Background to research and synopsis
An important stage of cancer metastasis is the transformation of polarized epithelial cells into motile mesenchymal cells with invasive properties, which is referred to as epithelial to mesenchymal transition (EMT).
Three-dimensional (3D) cell culture technologies that more closely resemble in vivo cell environments, can accommodate better precision in drug discovery and provide greater understanding of cellular mechanisms.
Our aim is to generate biomaterial based 3D cancer cell culture systems as a model to investigate the disease microenvironment. Polyhydroxyalkanoates (PHAs) are a family of naturally occurring intracellular polymers synthesized by a variety of microorganisms. We have previously optimised 3D models to study breast cancer metastasis.
This project will explore the cellular mechanisms associated with cancer metastasis in 2D and 3D cell cultures of human cancer cells. This will involve generating/optimising PHA based scaffolds, analysis of cancer cells using molecular biology (qRT-PCR, siRNA silencing/CRISPR), flow cytometry (cell cycle, apoptosis assays) and protein expression (immunocytochemistry, western blot). We will develop novel tools to part-replace animal models for longitudinal cancer biology investigations, drug screening, providing faster and clinically meaningful data, with a potential to transforming pre-clinical research to design a more efficient and bespoke treatment regime for patients.
Recent publications by supervisors that are relevant to the project
1. Kosgodage, US, Uysal-Onganer P, MacLatchy A, Nicholas AP, Inal JM, Lange S (2019). Peptidylarginine Deiminases Post-translationally deiminate Prohibitin and modulate Extracellular Vesicle Release and microRNAs in Glioblastoma Multiforme. Int J Mol Sci 20(1):103.
2. Kosgodage US, Uysal-Onganer P, MacLatchy A, Mould R, Nunn AV, Guy GW, Kraev I, Chatterton NP, Thomas EL, Inal JM, Bell JD, Lange S (2019). Cannabidiol Affects Extracellular Vesicle Release, miR21 and miR126, and Reduces Prohibitin Protein in Glioblastoma Multiforme Cells. Transl Oncol. 12(3):513-522.
3. Lukasiewicz, B., Basnett, P., Nigmatullin, R., Matharu, R., Knowles, J.C. and Roy, I. 2018. Binary Polyhydroxyalkanoate Systems for Soft Tissue Engineering. Acta Biomaterialia. 71, pp. 225-234.
4. Bagdadi, A., Safari, M., Dubey, P., Basnett, P., Sofokleous P., Humphrey E, Locke, I.C., Edirisinghe M., Terracciano C., Boccaccini, A.R., Knowles, J.C., Harding, S. and Roy, I. 2018. Poly(3-hydroxyoctanoate), a promising new material for cardiac tissue engineering. Journal of Tissue Engineering and Regenerative Medicine. 12 (1), pp. E495-E512.
5. Dart, D.A., Uysal Onganer, P. and Jiang, W.G. 2017. Prostate-specific PTen deletion in mice activates inflammatory microRNA expression pathways in the epithelium early in hyperplasia development. Oncogenesis. 14 (6), p. 400.
6. Koushyar, S., Grant, G.H. and Uysal Onganer, P. 2016. The interaction of Wnt-11 and signalling cascades in prostate cancer. Tumor Biology. 37 (10), pp. 13049-13057.
7. Kosgodage US, Mould R, Henley AB, Nunn AV, Guy GW, Thomas EL, Inal JM, Bell JD, Lange S (2018). Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer. Front Pharmacol. 9:889.
8. Lange S, Kholia S, Kosgodage US, Inal JM (2017) Treatment of Prostate Cancer Using Deimination Antagonists and Microvesicle Technology. In: Protein Deimination in Human Health and Disease, Volume II (Bhattacharya, S; Nicholas, A (Eds.)), Chapter 22. Springer ·ISBN10 3319582437.
9. Lange, S., Gallagher, M, Kholia, S., Kosgodage, U., Hristova, M., Hardy, J. and Inal, J.M. 2017. Peptidylarginine Deiminases-Roles in Cancer and Neurodegeneration and Possible Avenues for Therapeutic Intervention via Modulation of Exosome and Microvesicle (EMV) Release? International Journal of Molecular Sciences. 18 (1196).
Candidates should normally have a minimum classification of 2.1 in their Bachelor Degree or equivalent and preferably a Masters degree. Applicants whose secondary level education has not been conducted in the medium of English should also demonstrate evidence of appropriate English language proficiency normally defined as IELTS: 6.5 (overall score with not less than 6.0 in any of the individual elements).
Please follow this link to apply for the programme most appropriate to your research, please note that the programme appears as MPhil on UCAS, however there is an option on the form to request PhD via MPhil, which is the standard route:
To make your application for (SLS9):
Interviews will be held in June/July 2019. The Studentship title is SLS9 Full Scholarship and Fee Waiver School of Life Sciences. Please include this in your application, you must also list the Project Code in order for us to allocate your application to the correct.