We carry out our research here at Sanger and at our fieldsites in Kenya and Mali. We are working to answer the following questions using a variety of genomic tools from whole genome sequencing to single cell RNAseq.
Theme: Mosquito Vector Population Genomics
Species diversity in Anopheles: We carry out large scale whole genome sequencing projects on mosquitoes, and we are focused on a deeper understanding of diversity in African vectors in particular. We are building simple amplicon panels that can be used for any Anopheline to diagnose species, identify geographic origin, and determine if the mosquito is positive for Plasmodium parasites and if so, which species.
Anopheles funestus population genomics: We also lead the Anopheles funestus population genomics project to evaluate diversity and selection in this major malaria vector. This is collaboration with many scientists across Africa. In general, we use the whole genome sequence data we generate to explore population structure, understand selection, and improve the chances for gene drive success in the face of the vast amount of genetic diversity that segregates within African Anopheles species.
Project Neandersquito: To understand how populations have changed over time, we are generating whole genome sequence data from museum specimens of mosquitoes collected over the past century. We do this in a non-destructive way (otherwise curators would never let us touch their collections!).
High quality reference genomes: A good reference genome unlocks huge potential towards the study of an organism, and technology now makes this possible using single small insects. With support from the Bill and Melinda Gates Foundation, we are generating high quality reference genomes for understudied Anopheles vector species around the world using long-read and long-range sequencing technologies. We are also heavily involved in the Darwin Tree of Life Project, which aims to generate reference genomes for all 60,000 or so British eukaryotic species in the next decade.
Theme: Transmission biology of Plasmodium falciparum
Malaria Cell Atlas: We have pioneered the application of single cell transcriptional approaches to investigate individual Plasmodium parasites. We have created the Malaria Cell Atlas, which is freely available and interactive and displays how any gene is expressed at any point across the entire life cycle of parasites. We are also able to use the nucleotide variants from the transcriptional data to assign genetic identity to each cell, and thereby we can deconvolve natural mixed infections for the first time. Our next project is to incorporate wild parasites from P. falciparum, P. malariae, and P. ovale into our atlas.
Transmission Dynamics: We are using single cell RNAseq to to study the behavior of P. falciparum parasites from natural infections. How do malaria parasites behave inside of the human host to enhance their probability of transmission? In particular, using single cell approaches, we will interrogate the relationship of the asexual to sexual parasites in a given infection (are all asexual parasites contributing to the transmission pool?), and we will study whether parasites mate non-randomly inside the mosquito. This project is newly funded by the Medical Research Council and we will begin work in Mali at end of 2019.
All areas of our research are aimed at gaining a deep evolutionary understanding of these interesting yet deadly organisms, and ultimately our research and the data we generate will help to implement new methods of control, including gene drive and transmission blocking strategies that aim to stop malaria.