New outbreaks caused by bluetongue viruses (BTVs) have emerged in European livestock every year since 1998. These events that have been linked to climate change, resulted in massive losses due to fatalities, reduced productivity, reproductive failures, restricted animal movements/trade, and surveillance/vaccination costs. PALE-Blu brings together European institutes with expertise in BTV research and diagnosis, with partners in endemic regions (Africa, the Middle East and Turkey) that act as a ‘source’ for BTV strains that emerge in Europe. Full-genome sequence-analyses will increase the accuracy of BTV-strain distribution maps, to identify pathways and mechanisms for spread into and within Europe, as well as appropriate prevention strategies. PALE-Blu will analyse the genetic connectivity of Culicoides vector populations in different regions, as well as the movements of individual BTV lineages and genes. Together with reverse genetics technologies and infection/replication studies in new Culicoides cell lines, or adults from different Culicoides species, this will elucidate the genetic basis for geographic localisation/movement of BTV strains and serotypes. We will analyse differences in saliva proteins from Culicoides species, their ability to modify the BTV surface proteins (proteases) and effects on efficiency of transmission (in both directions) between vertebrae hosts and insect-vectors. These studies will provide a better understanding of incursion risks for different BTV strains, supporting effective control strategies. PALE-BLU will explore more effective and cross-serotype subunit-vaccines that are DIVA assay compatible and generate a stronger immune response from a single innoculation. We will also explore the potential for use of antiviral agents to induce immediate protection post vaccination. More effective diagnostic systems to better detect mixed infections will also be developed by multiplexing existing or novel diagnostic assay systems.