The current pandemic demonstrates how viruses represent a major threat for human health. Viral infection is a complex multistep process involving both the virus and the host cell machinery. The very first stage consists of landing and binding of the virus, followed by host cell entry, and then the release of the viral genetic material into the cell. Entry pathways are largely defined by the preliminary interactions between viruses and their receptors at the cell interface. Elucidating this complex interplay is a crucial step towards establishing a full picture of the infection process and may lead to the discovery of new antiviral drugs targeting viral entry. Our current knowledge of virus-host interactions mainly relies on the use of cancerous model cell lines cultured in 2D that far from mimic the 3D in vivo conditions of tissue, such as cell heterogeneity and complex organization. Hence, there is an urgent need to develop an innovative platform to monitor and quantify the molecular forces and dynamics at play during the entry pathways in such complex environments. The ambition of this proposal is to unravel virus-host interactions under physiologically relevant 3D conditions by combining single-virus atomic force microscopy and optical tweezer techniques. By means of cellular models of increasing complexity, we will decipher the complex relationship between the organization and heterogeneity of epithelium and the early stages of viral infection. At the frontiers of nanobiophysics and virology, this project will push the limits of advanced nanotechniques to understand the molecular mechanisms of virus entry in unprecedented 3D in vivo conditions. This project will have strong scientific and medical impacts. In virology, it will strongly enhance our molecular understanding of virus-host interactions. In medicine, our new methodology will contribute to the identification of new compounds that target viral infection and the innate immune response.

Overweight and obesity have reached worldwide epidemic level. Both overweight and obesity are characterized by comorbidities such as cardio-metabolic risk factors (i.e., insulin resistance, type 2 diabetes, hypertension, dyslipidemia, low-grade inflammation) representing a major public health problem. Therefore, it is urgent to find a therapeutic solution to target all these metabolic disorders. Among the environmental factors able to influence the individual susceptibility to gain weight and to develop metabolic disorders associated with obesity, we have contributed to the demonstration that gut bacteria (i.e, gut microbiota) influence host metabolism. We recently discovered a putative interesting microbial candidate, namely Akkermansia muciniphila. More exactly, we found that the administration of Akkermansia muciniphila reduced body weight gain, fat mass gain, glycemia, cholesterolemia and inflammatory markers in diet-induced obese mice. Moreover, in overweight/obese patients subjected to a calorie restriction diet, the higher abundance of Akkermansia muciniphila was associated with a better cardio-metabolic status. These observations suggested that the administration of Akkermansia muciniphila in overweight or obese people could be a very interesting therapeutic solution. Currently, no human study have investigated the beneficial effects of Akkermansia muciniphila administration on obesity and metabolic disorders. Thus, the main objective of this ERC POC project “Microbes4U” is to get the proof of concept in humans of the safety and efficacy of Akkermansia muciniphila administration in the treatment of overweight, obesity and metabolic disorders associated such as insulin resistance, type-2 diabetes and dyslipidemia.