Objetivo "The human gastrointestinal tract is colonized by an abundant and diverse bacterial microbiota that exist in a mutualistic relationship with the host that promotes intestinal health. Maladaptation in this host microbial dialogue leads to a deranged inflammatory response and inflammatory bowel disease (IBD) that can progress to colon cancer. The complex interplay between genetic and environmental factors and their impact on intestinal inflammation are starting to be deciphered in IBD, however little is known about how they influence the transition from colitis to cancer. We recently established a relevant model of bacteria-driven invasive colon cancer and have mapped both genetic and immune pathways that perpetuate disease. Genetic susceptibility maps to a 1.7mb region on chromosome 3 containing the candidate gene Alpk1, an alpha-kinase. This locus mediates its effects through the IL-23 driven innate lymphoid cell response and we have identified the cytokine IL-22 as a key player in driving the tumour cell response. We will use a multi-disciplinary approach to probe the interaction between genetics, microbial drivers and inflammatory pathways that promote colon cancer. BAC transgenics and cell-type specific knock-out mice will be used to establish the function of Alpk1 in bacteria driven colon cancer. In vivo models will be complemented by novel 3D colonic organoid and crypt cultures generated from epithelial stem cells from normal or tumor tissue allowing analysis of microbial and cytokine signals that influence intestinal epithelial cell and stem cell function. Deep sequencing combined with bacterial cell culture will identify changes in the intestinal microbiota that drive tumourigenesis. Results from mouse models will be translated to analysis of human colorectal cancer. These studies will uncover new pathways involved in bacterial interaction, intestinal inflammation and tumour formation that may offer new therapeutic targets in IBD and colon cancer." Ámbito científico natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesclinical medicinegastroenterologyinflammatory bowel diseasemedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologycolorectal cancernatural sciencesbiological sciencesgeneticschromosomes Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Convocatoria de propuestas ERC-2013-ADG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Aportación de la UE € 2 484 620,00 Dirección WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Reino Unido Ver en el mapa Región South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Tipo de actividad Higher or Secondary Education Establishments Investigador principal Fiona M Powrie (Prof.) Contacto administrativo Gill Wells (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Reino Unido Aportación de la UE € 2 484 620,00 Dirección WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford Ver en el mapa Región South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Tipo de actividad Higher or Secondary Education Establishments Investigador principal Fiona M Powrie (Prof.) Contacto administrativo Gill Wells (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos