Enterovirus infections are of public health concern as globally millions of people become infected each year. Enteroviruses (HEV) are an assemblage of highly diverse positive-stranded RNA viruses that belong to the Picornaviridae family. Four out of the 13 known enterovirus species are human pathogens, with poliovirus being the most prominent member. The entry point for these viruses is the gastrointestinal or the respiratory tract from where they can spread to other organs and cause severe pathologies. Vaccines exist only against polio and no therapies are currently available against any HEV. Thus, there is a great need for new antivirals. I aim to identify host factors crucial for the HEV life cycle by performing a whole genome CRISPR loss-of-function screen in primary cultures of human intestinal epithelial cells. Importantly, the lytic nature of HEVs will allow a straightforward selection of cells that survive virus infection upon small guide RNA-mediated deletion of host genes that support HEV infection. This interdisciplinary project demands expertise both in stem cell, enterovirus biology and host-pathogen interaction, which is provided by the Jensen lab (host), the Tapparel lab (partner) and myself, respectively. Through access to intestinal stem cells and organoids from various donors and multiple HEVs I have the unique possibility to dissect host-enterovirus interactions by taking host and virus variations into account. By integrating this data, I will be able to dissect tropism both from a host and a pathogen perspective, and identify host factors that are necessary for HEV infection. This knowledge will contribute to the discovery of novel drug targets for broad-spectrum therapies against HEV infections and moreover provide me with the unique opportunity to move forward in academia and establish my own research group.

Humans are microbial, living in close functional interaction with their skin and mucosal microbiomes. Human-microbes interplay has proven essential for the maintenance of health and well-being and profiling of microbiomes will become an essential feature of the personalized preventive nutrition and medicine of tomorrow. Europe has gained a leading position in microbiome science and yet to fulfill societal expectations, an international consensus will be essential on key aspects. These include i) clinical trial design as well as analytical standards, ii) definitions of healthy microbiomes as a function of numerous factors, accounting for confounders, iii) means of demonstrating causality of altered host-microbes interactions in diseases and iv) processes for the development of clinically relevant, validated biomarkers. The International Human Microbiome Concertation and Support Action (IHMCSA) will tackle all necessary steps to open the perspective of managing nutrition and health of the microbial human. Involving key stakeholders representing the multiplicity of actors concerned, including citizens, IHMCSA will map existing material, delineate necessary steps and pathways for innovation and build consensus on priorities and means for the future of microbiome science and its translation. This will lead to recommendations, validated by an international Strategic Steering Committee as well as academies of medicine of the world, directed to the European Commission, international research programmes, funding and regulatory agencies and decision makers of health systems. To ensure sustainability of the proposed measures, IHMCSA will promote unified repositories for sharing standards, SOPs and data, and contribute to the structuration of the European Microbiome Centers Consortium with a role in gathering world microbiome networks of excellence. With IHMCSA, human-associated microbiomes will be recognized for their true value in contributing to secure the future of mankind.