Insect vectors durably transmit many important human and animal diseases. Insects are mobile, adaptable and difficult to control, which makes them efficient vehicles for disease emergence, spread and maintenance. Genomic tools have been applied to the study of vectors and vector control, and some insects such as the African malaria vector Anopheles gambiae have now become new model organisms for natural host-pathogen interactions. We study mosquito vectors of malaria and arboviruses, which generates four main kinds of large-scale data that requires dedicated bioinformatics expertise: i) functional dissection of mosquito immune signaling pathways by RNAseq transcriptome profiling to detect responses to pathogen infection and/or silencing of target genes, including mRNA as well as small and other non-coding RNAs, ii) next-gen genetic linkage mapping by deep sequencing of index-tagged phenotyped individual mosquitoes, iii) population genomic analysis by whole-genome sequencing of hundreds of individual 250Mb mosquito genomes, iv) metagenomic analysis of the mosquito microbiome and pathogen susceptibility, and of ecological metagenomic communities in field samples of mosquito vectors.

We are involved, in collboration with the WHO, in the SaMARA which aims at detecting the emergence of antimalarial drug resistance in Africa. Samples (dried blood spots) are collected from the Nantional Malaria Control Programmes in Africa during clinical efficacy studies. My group at the Institut Pasteur in collaboration with the Institut Cochin (Frédéric Ariey) tested these samples and assessed the proportion of parasites harboring SNPs or CNV associated to antimalarial drug resistance. We have previously demonstrated that mutations in the propeller dommain of a Kelch gene located on the chromosome 13 are strongly predictive of artemsinin resistance. Until last year, artemisinin resistance was confined in South east Asia. Recently, we have detected in African samples a high proportion of mutant parasites. This mutation has never been observed before in South east Asia. To perform comprenhensive genomic analysis, we have sequenced (Illumina) all mutants (=24) and paired wild type samples. Analysis of these sequences (and 400 whole genome sequences from parasites collected in Asia, Africa and America, upload on a dedicated website) should allow to: - define if the mutants have emerged locally or have spread from Asia - define the genetic background of these mutants (are specific alleles facilitated the emergence of K13 mutantions) - describe the genomic profile(s) of these mutants (especially the haplotypes associated to multidrug resistance)

Comparison of Microsatellites and Multi Locus Sequences Typing approaches. Fungi: Pneumocytis jirovecii

In this project, we aim to identify P. vivax ligands involved in host cell invasion and understand how P. vivax has gained the capacity to infect reticulocytes from Duffy-negative individuals. Our strategy will be based on a 2-step approach by taking full advantage of next-generation sequencing and functional biological analysis (including in vitro invasion assays and infection in humanized mice) and by availing our access to P. vivax isolates from both Duffy-negative and Duffy-positive vivax malaria patients in Madagascar. This strategy should explore and charactere the full repertoire of parasite ligands involved in invasion of human reticulocytes in Malagasy malaria endemic settings where two human populations with distinct Duffy blood group phenotypes (Duffy-negative and Duffy-positive) are frequently exposed to P. vivax. The main objectives of this project are to uncover the molecular basis for the ability of P. vivax to infect reticulocytes from Duffy-positive and Duffy-negative individuals by identifying and defining the role of parasite ligands (including erythrocyte binding proteins (PvEBPs) and reticulocyte binding proteins (PvRBPs)) in mediating invasion and explore the feasibility of targeting combinations of P. vivax invasion related proteins with antibodies to block invasion with high efficiency.