PhD Studentship: Unravelling the Role of Genotoxic E. Coli in Colorectal Cancer

Major supervisor – Dr Stephanie Schüller

Colorectal most cancers (CRC) is the third most typical and second most deadly most cancers globally. Most circumstances of CRC usually are not hereditary however influenced by life-style components and adjustments within the intestine microbiome. Importantly, 5-10% of CRCs have been linked to E. coli strains producing the metabolite colibactin which causes DNA injury and mutagenesis in colonic epithelial cells. Apparently, latest work has proven that colibactin expression is highest underneath microaerobic situations much like these within the colon. Moreover, irritation and mucus depletion promote colibactin manufacturing and carcinogenesis indicating a task of the intestine atmosphere in regulation of colibactin expression. Along with colonic oncogenesis, colibactin additionally kills sure intestine micro organism suggesting an evolutionary position in interbacterial competitors. Given the affect of colibactin and the microbiome in CRC growth, it’s essential to know how colibactin manufacturing is regulated within the human intestine and the way it impacts the intestine microbiome.

On this PhD venture funded by Huge C most cancers charity, we are going to use a physiologically related microaerobic, mucus-producing human colonic cell and organoid mannequin which permits co-culture with oxygen-sensitive intestine micro organism to analyze 1) the affect of chemical cues and commensal micro organism on colibactin expression, 2) the interplay of genotoxic E. coli with the colonic epithelium, and three) the affect of genotoxic E. coli on the intestine microbiome.

Taken collectively, insights gained from this work will inform the event of therapies focused at E. coli-associated CRC via colibactin inhibition and the identification of bacterial biomarkers for high-risk populations.

This venture can be suited to a motivated pupil with a background in microbiology & cell biology and related analysis expertise. You’ll be a part of an interdisciplinary and supportive analysis atmosphere on the UEA Medical College and carefully collaborate with the groups of Prof Nathalie Juge (Quadram Institute) and Prof Jean-Philippe Nougayrède (College of Toulouse). Professional coaching in bacterial, intestinal cell and organoid tradition, analysis of epithelial operate, molecular biology, microbiome evaluation and bioimaging can be offered.

Entry necessities

The usual minimal entry requirement is 2:1 in Organic Sciences.

References

i) Nougayrède JP, Homburg S, Taieb F, Boury M, Brzuszkiewicz E, Gottschalk G, et al. (2006) Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science313(5788):848-51.

ii) McGrath CJ, Laveckis E, Bell A, Crost E, Juge N & Schüller S. (2022) Growth of a novel human intestinal mannequin to elucidate the impact of anaerobic commensals on Escherichia coli an infection. Dis Mannequin Mech. 15(4):dmm049365.

iii) Bossuet N, Guyonnet C, Chagneau CV, Tang-Fichaux M, Penary M, Loubet D, Branchu P, Oswald E & Nougayrede JP (2023) Oxygen focus modulates colibactin manufacturing. Intestine microbes. 2023;15(1):2222437.

iv) Sato T et al. (2011) Lengthy-term enlargement of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141(5):1762-72.

v) Krsek D, Yara DA, Hrbáčková H, Daniel O, Mančíková A, Schüller S* & Bielaszewska M*. (2023) Translocation of outer membrane vesicles from enterohemorrhagic Escherichia coli O157 throughout the intestinal epithelial barrier. Entrance Microbiol. 14:1198945.

Further Funding Info

This can be a totally funded studentship which covers tuition charges at House price price and offers an annual stipend of £19,162 and £1,000 every year to assist analysis coaching.