The C2 project focuses on the interaction of nutritional intake with the resident microbiome and the intestinal mucosa. It uses two complementary experimental systems (Drosophila (C2.1, PI Roeder) and mouse (C2.2, PI Rosenstiel)) to tackle the same scientific problems.
A key observation is that alterations of this tripartite interaction (e.g. during malnutrition) have an influence on the immunological integrity of the mucosal barrier and change responses of the host. We will follow observations from both subprojects that have been obtained during the first funding period. Phases of malnourishment have lasting “memory” effects on both host and microbiota and we will delineate molecular mechanisms that are responsible for the long-term shifts of gene expression and cellular programs.
In a second part of the project, we will pursue the hypothesis that ageing effects are partially mediated by a complex interaction of microbiota and (endogenous) malabsorption, which reflects a similar scenario as observed in exogenous protein energy malnutrition (PEM).
We will continue with our main focus on the intestinal epithelium as a mediator between the microbiota, environmental influences (i.e. dietary factors) and the host, but also investigate the communication of the epithelium with different other cell types, in which the lasting changes occur (e.g. immune cells, insulin producing cells). We will employ innovative tools and methods such as conditional transgenic animals to elucidate the epigenetic machinery in specific cell types and single cell sequencing to delineate the exact molecular changes imprinted by PEM in vulnerable phases of development.