Overview
Our research lies at the interface of genomics, epidemiology, and ecology as applied to the study of vector-borne infectious disease transmission dynamics, including tropical diseases such as malaria. By combining fieldwork studies in Africa, genomic tools, and experimental and computational analyses, our research aims to provide novel insights into diverse biological and evolutionary aspects of malaria parasites and vectors. We also develop new genomic protocols and informatics tools to address key questions in infectious diseases. We are pursuing these goals through three main research areas, highlighted below.
Patterns of within-vector malaria parasite diversity
Plasmodium falciparum undergoes asexual reproduction within the human host but reproduces sexually within its vector host, the Anopheles mosquito. Thus, the mosquito stage of the parasite life cycle provides an opportunity to create genetically diverse parasites in mixed-infected mosquitoes, potentially increasing parasite population diversity. Albeit the generation of genetic diversity arises within vectors, most of genetic investigations of P. falciparum have focused on the parasite life stages in the human host. Studies of within-vector (and human host) P. falciparum diversity is challenging because of the difficulties to obtain parasite genomes due to the high ratio host-to-parasite DNA and low parasite loads. To overcome this technical challenge, we developed a multiplexed genome capture method that enables nearly full P. falciparum genome sequencing directly from field mosquitoes. The lab is currently adopting this newly developed and scalable method to assess the extent of P. falciparum diversity and the rate and relatedness of mixed infections in natural Anopheles mosquitoes. By applying comparative genomic and population genetic analyses of P. falciparum infecting mosquitoes and humans, we aim to better understand mechanisms of sustained parasite diversity and malaria transmission in natural settings.
Genomic perspectives on the evolution and transmission dynamics of malaria parasites
Genomic surveillance of malaria parasite populations is a powerful tool to understand the transmission dynamics and monitor parasite diversity and population connectivity as malaria control interventions are applied. In Zambia, despite intensified control interventions, P. falciparum malaria remains endemic but with heterogeneity in transmission levels and infection prevalence, which pose challenges to achieving and sustaining malaria elimination. Our lab is conducting whole genome sequencing of P. falciparum samples from nationally representative population-based household surveys. Through analysis of polymorphisms in the parasite genomes, we seek to understand the transmission patterns and spatial scale of parasite connectivity at the national level. This research will aid evaluation of interventions and power improvements in preemptive control measures and resource allocation that aim to disrupt malaria transmission.
Metagenomic profiling of pathogens and microbes associated with arthropod vectors
The discovery and monitoring of novel pathogens and ecologically-associated microbes in natural populations of Anopheles and other arthropod vectors has been hampered by the lack of rapid and accurate analytical pipelines that can reconstruct the mixture of organisms from metagenomic data. In collaboration with Microsoft Research (Project PREMONITION) we are developing a novel, scalable entomological monitoring platform that harnesses advances in arthropod collection and next generation “deep” sequencing methods to convert biological samples into digital genomic data. Our lab utilizes the latest genomics technology developed by Oxford Nanopore Technology and optimizes protocols for field deployable sequencing of mosquitoes. In combination with a cloud-scale metagenomic pipeline, we seek to characterize pathogens and microbes associated with natural mosquito vectors, with a particular focus on Anopheles malaria vectors.