Genomic perspectives on disease transmission

Mosquitoes are not passive vessels for Plasmodium malaria parasites. Plasmodium¬†parasites participate in complex biological interactions with mosquitoes and pass through several developmental life stages before a mosquito is rendered infective and capable of spreading the parasites to a new host. These elaborate interactions are likely the reason why only mosquitoes in the genus Anopheles are capable of spreading human malaria parasites, and further, why only approximately 60 of the more…

Development of DNA analysis methods for molecular epidemiology

As genomic data moves from the realm of basic research to being useful in translational applications, analysis tools to expedite efficient extraction of epidemiologically relevant information become valuable. The exploration and application of new genomic or transcriptomic data types to the malaria realm, such as linked ‘read cloud’ data, usually requires new analysis approachesto contend with the skewed nucleotide composition in parasite genomes, or high heterozygosity and repetitiveness in mosquito…

Evolution of resistance to anti-malarial drugs and insecticides

Drugs and insecticides are intense agents of natural selection on parasite and vector populations. This selection pressure leaves a characteristic wake in the genomic vicinity of resistance mutations. By sequencing contemporaneous collections of parasites and vectors, or sequencing samples from longitudinal collections that span the origin of resistance, we can identify the mutations that directly confer resistance or that tune high-fitness resistance genotypes through compensatory or epistatic effects.

Drivers of parasite antigenic diversity and consequences for vaccine efficacy

Like many infectious agents, malaria parasite populations harbor antigenic diversity because it confers a fitness advantage in the context of adaptive host immunity. Antigenic diversity is not unstructured, however. It is organized by rules deriving from humoral and/or cellular cross-protective immunity, and it is bounded by functional constraint. If better understood, these rules that structure antigenic diversity could inform the rational design of future vaccines.¬† Though the first malaria vaccine…