Fungal infections have a major impact on human health, infecting about 2 billion people and killing more people each year than malaria or breast cancer. In particular, Candida species impose a high clinical and economic burden upon the European population. They frequently cause fatal hospital-acquired bloodstream infections. They also cause oral thrush and vaginitis. Most women have suffered an episode of vulvovaginal candidiasis, with ~8% enduring recurrent infections. The initiation and severity of a Candida infection depends on an intricate interplay between the infecting fungal strain and the individual’s immune status and microbiota, all of which can display significant variability. Therefore, for the first time, FunHoMic integrates experts in fungal pathogenesis, immunology, microbial ecology and ‘omics technologies to train 13 Early Stage Researchers (ESRs) who will define and exploit this Fungal-Host-Microbiota interplay to identify novel biomarkers (fungal or host genetic polymorphisms, microbiota profiles, metabolites or immune markers) for the stratification of a patient’s risk of serious fungal infection. This will pave the way for precision medicine in patient management through preventive or therapeutic interventions using antifungals, immune modulators or Live Biotherapeutic Products (LBPs). FunHoMic ESRs will gain broad interdisciplinary skills plus a translational mindset through our integrated, inter-sectoral training program. This will allow Europe to remain at the forefront of translational research in the field of medical mycology. To achieve this vision FunHoMic unites academic partners from France, Germany, The Netherlands, Switzerland, Spain and UK, a French Technology Research Institute with cutting-edge ‘omics technology platforms and three SMEs from The Netherlands, Belgium and France that bring unrivalled organ-on-chip and gastro-intestinal tract simulation technologies and expertise in the development and exploitation of innovative LBPs.

Inflammatory bowel diseases (IBD) are the second most common immune-mediated disorders in Europe, affecting more particularly young people. The current therapies, including antibodies, show three main drawbacks: efficacy, tolerability and convenience. NEW DEAL solution will offer radical therapeutic progress for all IBD patients, thanks to the improved efficacy and increased safety of the specific JAK3 inhibition, which has been proven in clinics to be a target of great interest, the better tolerability of siRNA in term of immunogenicity and the good convenience with oral administration. To achieve this challenge, we will address three objectives: i) Specifically inhibit JAK 3 in a highly selective and safer manner by the mean of siRNA carefully designed and validated, ii) Deliver the siRNA therapeutic locally to the inflamed gut, by combining innovative nanostructured lipid carriers enabling their transport across the mucus, the intestinal barrier and the plasma membrane of the target cells, with polymeric capsules for protecting siRNA nanotherapeutics during their transit along the GI tract, thus allowing an oral administration, and iii) Promote the clinical translation and the future industrial transfer of this new clinical product, by addressing manufacturing, safety and efficacy evaluation at the late preclinical stage, to generate a Regulatory Submission Package and a Clinical Development Plan. The NEW DEAL project brings together clinical experts on IBD, leading scientists in nanomedicine, RNAi biology and immunology, innovative SMEs with a strong background in nanosafety, design of capsules and regulatory issues and an established pharma company with historic expertise on gastroenterology medicinal products. If successful, NEW DEAL will open new avenues for siRNA-based therapy in IBD with oral administration.