Defining the molecular determinants required for Leishmania life cycle progression and virulence

Leishmania are parasites that cause diseases affecting the poorest communities globally. 15 years ago we sequenced all the genes in this parasite but have made limited progress in connecting these genes to parasite infectivity, due to our limited ability to perform genome-wide experiments. However, using CRISPR genome modification tools we have developed approaches for genome-wide functional analysis. We will delete each gene individually generating 9000 Leishmania mutants which we will use to infect mice to determine if that gene is important for causing disease. In parallel we will tag 3000 proteins with a fluorescent marker enabling us to work out where in the cell this protein is found, helping to define its function. By combining this positional and functional information we will discover the most important pathways for parasite infectivity and then will dissect their specific functions in more detail, which will identify new ways to treat these diseases.