The intestine provides an attractive route to model biologically important intestinal processes and a unique opportunity for the direct identification and analysis of factors that contribute to development and maintenance of both normal as well as the development of neoplasia. However, little is known about intestinal stem cell components in crypt reproduction, stem cell niche, the clonal architecture & the lineage relationships of normal and neoplastic intestinal crypts (in both benign & malignant disease).
Under normal conditions, a division rate of stem cell is carefully regulated, in order to produce new cells to ensure daily regeneration of the gut epithelium. It has been known that errors in the genome of stem cells or alteration of stem cell niche that trigger cell division of stem cells often lead to bowel diseases (e.g., IBD) and colorectal cancer. Currently, colorectal cancer kills approximately 500K people a year worldwide. To create a clinically relevant model of CRC, we have developed and validated genetically modified organoids and patient-derived tissue explants from surgeries in Nottingham hospitals as platforms to study:
1) The mechanisms underpinning intestinal stem cell-driven tissue renewal
2) The development of new technologies for organ replacement using cell and organoid-based transplantation and reprograming
3) Understand molecular regulation of key controllers of tumour growth, invasion and dissemination, metastatic colonization, and chemotherapy response of cancer cells
4) Identification of drug(s) selectively targeting colorectal cancer stem-like cells for differentiation, called differentiation therapy
These projects will provide training in a broad set of techniques through key cellular signalling, genetics and molecular biology, next-generation sequencing (NGS) and single-cell multi-omic technologies, immunohistochemistry, live imaging & confocal microscopy, validation and screening potential anti-cancer drugs.
If you have any queries about applying, please contact by Email:
[email protected] or you can apply directly through our online application:
https://www.nottingham.ac.uk/pgstudy/how-to-apply/research.aspx PhD or MRes academic state dates are the 1st October, December, February, April and July each year.
Please include in your application:
• Copies of your Academic certificates
• A recent biography (CV)
• Names and email addresses of 2-3 referees
• A statement or covering letter highlighting any of laboratory training and research experiences
• Research proposal (name the named supervisor for the research project proposed here or contact your supervisor by email:
[email protected] • English certificate (If English isn’t your first language)
Funding Notes
For these projects, we consider applications from sponsored and self-funded prospective students worldwide with:
• good biology, biomedical, medical or related degree, with interests in any of the areas outlined above,
• a good command of the English language (written and spoken) as outlined in the postgraduate prospectus,
• competence with computers and data handling,
• a source of funding to cover tuition fees and bench fees (note that tuition fees are different for Home and EU students than for International students). More information regarding fees can be found under the ‘Medicine’ heading at; View Website
References
Sato, T. & Clevers, H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340, 1190-1194 (2013).
Ahmed, M. et al. Repurposing Antibacterial AM404 as a Potential Anticancer Drug for Targeting Colorectal Cancer Stem-Like Cells. Cancers (Basel). 2019 Dec 31;12(1).
Majumder B. et al., Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity. Nat Commun. 2015 Feb 27;6:6169.
Babaei-Jadidi, R. et al. FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. J Exp Med 208, 295-312 (2011).
Li, N. et al. An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance. Oncogenesis. 2019 Feb 19;8(3):13.
