The study of intestinal infection, inflammation, and regeneration.

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This research project is aimed to understand how the body deals with tissue damage. This damage can either be caused by the development of an inflammatory immune response after infection, or by 'treatment-induced damage' such as exposure to radiation or by toxic chemicals. Many (cancer) patient groups will have to deal with similar amounts of tissue damage. The different 'causes' of damage require specific and appropriate responses. Unfortunately, the complexity of tissue repair is not something that can easily be studied using cell culture, and thus animal models are necessary.

There are various subsets of immune and non-immune cells in the intestine that tightly control homeostasis. When they are perturbed by infection, chemicals or genetic predisposition, these cells can cause diseases including inflammatory bowel diseases (IBDs), food allergies and intestinal cancers. Understanding the molecular and cellular principles underlying intestinal inflammation and regeneration represents a potential target for identifying novel therapeutics for the treatment of these diseases. We will use mouse models of intestinal infection and damage, ultimately using 678 mice for this research project. Unfortunately we cannot avoid a certain amount of distress as we first need to generate damage in order to study the repair process. However, during and after damage we will very closely monitor these animals to prevent unnecessary suffering.

Fortunately, we have developed ex vivo models to study specific mechanistic aspects of intestinal diseases. These 'organoids' will be used for all mechanistic studies, greatly reducing the amount of animals normally required for this project. Further, we strive to reduce the numbers further by using multiple tissues from each mouse at each endpoint.