Malaria and other diseases transmitted by mosquitoes and other vector insects impose substantial morbidity and mortality on human populations around the globe. The renewed call for malaria eradication, and the integration of genomics with studies of vector and parasite biology, provide a variety of new opportunities to understand in greater depth the basic biology of malaria and to develop new approaches to reducing disease incidence and monitoring the effectiveness of existing and evolving interventions being deployed to eliminate malaria.
Malaria vector genomics and genetic associations
We are developing and utilizing genomically-based tools to understand population and species structure in malaria vectors, and to map genetic associations for key traits (e.g., vector competence, host preference, insecticide resistance) in vector mosquitoes that affect malaria transmission and vector control. On-going projects include use a genome-wide single nucleotide polymorphism array for Anopheles gambiae we have developed with collaborators to map population structure and genetic associations, genomic analysis of species complexity among anopheline mosquitoes, and development of methods for discovery of genetic associations based on direct sequencing of well-defined mosquito phenotype pools.
Genetics and mechanisms of insecticide resistance
The use of insecticides, in insecticide-treated bed nets and indoor residual spraying, remains our most effective tool for reducing malaria incidence, but development of insecticide resistance in vector mosquitoes threatens to compromise the effectiveness of these tools. We are taking a number of approaches to investigating mechanisms and incidence of insecticide resistance in vector mosquitoes. On-going projects include collaborative efforts to map genetic variation associated with insecticide resistance in African vector mosquitoes, and the use of forward genetics to define mechanisms underlying target-site and metabolic resistance in anopheline vector mosquitoes and the model fruit fly Drosophila melanogaster.
Malaria parasite proteasome function
Development of new anti-malarial drugs will be accelerated by identification of “druggable” targets and processes in malaria parasites. We are investigating the function of the proteasome in Plasmodium falciparum to better understand its roles in parasite development, with an emphasis on asexual parasite stages that arise during erythrocytic parasite development. On-going projects include the use of small-molecule inhibitors to define the functional roles of the proteasome during blood-stage parasite development, analysis of ubiquitylation during parasite development, and genetic analysis of the development of resistance to proteasome inhibitors in malaria parasites.