| Project Detail |
Skin diseases affect 900 million people worldwide. Despite major efforts gaining insights in the disease mechanisms underlying Atopic Dermatitis (AD), the most common inflammatory skin disease (ISD), an effective treatment is currently lacking. AD is accompanied by skin and gut microbiota dysbiosis, suggesting an uncharacterized interplay between skin and gut. Furthermore, antimicrobial peptides (AMPs) that limit growth of bacteria in the host, were found deregulated in ISDs and Inflammatory Bowel Disease. Most of the host-microbe interactions are mediated by microbial metabolites that can spread and affect distant organs. INTERACT will investigate how skin microbial metabolites influence skin and gut inflammation through innovative research at two world leading research Universities, the Medical University of Vienna, Austria and University of California San Diego, USA under the supervision of Profs. Erwin Wagner and Richard Gallo, respectively.
Recent results from the applicant demonstrated gut alterations with neutrophilic infiltration and increased fecal AMPs in a genetically engineered mouse model (GEMM) of AD generated in E. Wagner’s laboratory. Hence, this study will test the hypothesis that skin-derived microbial metabolites promote skin-gut inflammation inducing AMP expression and neutrophil recruitment. Using state of the art technologies, such as metabolomics and novel GEMMs, as well as patient-derived material, this project will determine the therapeutic and biomarker potential of microbial metabolites, which will have profound implications for ISD.
The experimental approach combines the applicant’s expertise in host-microbe interactions with E. Wagner´s competence in mouse genetics and inflammatory diseases, as well as R. Gallo´s knowledge of AMPs and skin microbiome.
The MSCA PF will support the applicant´s career development by fostering acquisition of mechanistic and complementary skills, while studying a global health problem and economic challenge. |
