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:
a.nateri@nottingham.ac.uk 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:
a.nateri@nottingham.ac.uk • English certificate (If English isn’t your first language)