Final Report Summary - SYSBIOFUN (The interaction landscape between microbial colonization and functional genome of the host: a systems biology approach in fungal infections) The SysBioFun project has built up an interdisciplinary platform of clinicians, immunologists, geneticists and system biologists to uncover novel pathophysiological processes important for fungal diseases, which can form the basis of novel diagnostic and treatment strategies in these infections. The project was successful in the recruitment of large groups of healthy volunteers within the Human Functional Genomics cohort in which the complex interaction of genetic, microbiome and environmental factors are studied to determine the factors influencing host defense against fungi and other microbial pathogens. In addition, the project recruited the largest cohorts of patients to date with disseminated and vaginal Candida infection, in which we investigate which are the defects leading to the increase susceptibility to these severe infections. The success of building this infrastructure and team of experts resulted in already successfully identifying three new genes and genetic variants leading to an increased risk for the infection. Moreover, we identified novel markers for infection, as well as changes in skin microbial colonization that contributes to the increased susceptibility to fungal infections in patients with chronic mucocutaneous candidiasis. The research consortium has also important aims in improving patient care through identification of novel diagnostic and therapeutic approaches. In line with this, we have designed a set of immunological tests that are able to identify patients with an increased susceptibility to fungal infections. Finally, we have also performed a proof-of-principle clinical study with recombinant interferon-gamma that demonstrates that immunotherapy is a viable approach to correct the immunological defects in patients with systemic fungal infections.
