Chronic inflammation of microbial etiology has been suggested as the underlying cause of several debilitating conditions, particularly in patients afflicted with inflammatory bowel disease (IBD) or certain forms of malignancies. In this project, we will work along the central hypothesis that microbes, including commensals, represent a major cause for inflammation-induced immunopathology in genetically susceptible individuals. To address this issue, we will use two distinct mouse mutants with defined genetic alterations affecting the hematopoietic and the radio-resistant compartment, respectively. In particular, we aim to provide a detailed analysis of the molecular and cellular processes involved in microbe-associated pathogenesis in a model of myeloproliferative disorder and a model of IBD. We anticipate that the planned investigations will not only extend our current knowledge on the role of microorganisms as trigger of inflammatory disorders and cancer; they may also help to develop treatment strategies with potential translation into the clinic or to define new genetic markers of disease susceptibility, thereby allowing targeted preventive care.