Research Areas

The steady increase in global temperatures is dramatically reshaping the human-wildlife interface, exposing a large and completely naïve human and livestock population to wildlife species reservoirs and vectors. This is particularly worrisome as some arboviruses are associated with a wide spectrum of pathogeneses ranging from neurotoxicity in adults (e.g. West-Nile virus) and newborns (e.g. Zika virus), to severe haemorrhagic outcomes (e.g. Dengue virus and Yellow-Fever virus).

The ultimate goal of the group is to identify and characterize viral and cellular determinants responsible for each disease outcome to illuminate mechanisms of pathogenesis and identify promising targets for therapeutic intervention.

Profiling of arbovirus-induced perturbations using mass spectrometry

The ability of a virus to exploit multiple cellular machineries is essential to establish replication and transmission. This is often accomplished through direct binding of specific cellular proteins (i.e. protein-protein interactions), perturbation of the proteostasis of a subset of cellular proteins (i.e. protein stability) or modulation of the activity of entire cellular pathways through chemical modification of key signalling components (i.e. post-translational modifications). To identify such critical cellular “hubs” we are profiling arbovirus-induced perturbations using the latest generation of bottom-up MS-based approaches.

Identification and characterization of viral and cellular determinants of arboviral pathogenesis

Virus-induced changes as a whole contribute to the tropism of certain viruses for given species, tissues or cellular types, and at the same time are responsible for the specific pathological outcome of viral infections. The group tests the functional relevance of newly identified cellular factors for virus replication in different species and for different related and unrelated arboviruses, complementing large-scale genetic depletion/overexpression screens, with site-directed mutagenesis to map binding sites and identify potentially druggable surfaces. In a complementary line of research, the role of selected host factors in pathogenesis and morbidity is studied in relevant murine models.

Identification and characterization of viral and cellular determinants of host adaptation and transmission in arthropods and mammalians

One of the most puzzling traits of arboviruses is their ability to be transmitted by mosquitoes and ticks, while persisting in nature in highly diverse zoonotic reservoir species. However, it is not fully understood how evolution in different reservoir hosts has shaped replication and pathogenesis following infection in humans. To shed light on determinants of intermediate host adaptation and tropism, the group systematically screens host factor dependencies in viruses transmitted by distinct vectors in divergent cellular backgrounds. The long-term goal of these studies is to understand how long- and short-term evolutionary pressure can create virus variants allowing for a sudden increase of viral fitness or alternative tissue tropism.