ARBOVIRUS SKIN INFECTION MODELLING FOR MORE ACCURATE VIRAL PATHOGENESIS

Although inflammatory and neurological diseases caused by arthropod-borne viruses progress worldwide, biomedical advances are slow, still leaving patients to palliative care. New approaches to arboviral pathogenesis are needed to overcome the limitations imposed by inappropriate experimental systems. Here I propose to use tissue-engineered human skin, comprising immune cells and sensory nerve cells, and naturally-infected mosquitos to investigate infection and cell responses to the Dengue arbovirus. I will benefit from the host organization experience to perform (i) primary and induced pluripotent stem cell cultures and differentiation of dendritic cells, macrophages and sensory neurons, followed by their three-dimensional assembly, (ii) Dengue virus infection of mosquitos and (iii) analysis of cell infection and cell responses using virology, molecular biology and microscopy tools. In return, I will apply my skills in single cell transcriptomics of skin to explore the feasibility to apply this new technology to reconstructed tissue. Thanks to excellent scientific and soft skill training as well as the favourable arrangements provided by the host organization, the deliverables of this interdisciplinary research programme should be attainable in 24 months. In addition, I aim to gain professional maturity by proposing new projects for financing as a result of ideas, knowledge and collaborative links. The demonstration that human sensory neurons are infected by the Dengue virus in reconstructed skin should make an important impact for new biomedical approaches to prevent/treat neurological diseases caused by arboviruses. My objective is also is to have contributed to the progress of the host organization while evolving professionally for a stable employment in Europe.