GCID Parasite and Vector Genomics Project

Malaria holds the ignominious distinction of causing greater harm to public health than all other parasitic diseases combined. Malaria exacts a stunning toll of morbidity, mortality, and economic stagnation in tropical and sub-tropical developing nations around the world, causing hundreds of millions of clinical cases each year and almost a half million deaths, mostly in young children. Although disease elimination efforts in the mid-twentieth century under the World Health Organization (WHO) Global Malaria Eradication Program resulted in a substantial global reduction of malaria infections — primarily through vector control — these gains were ultimately temporary, demonstrating that we cannot become reliant on a single measure to control malaria. It is increasingly clear that combined approaches offering effective treatment of infected individuals and control of parasite transmission at a population level will be required for sustained malaria control and elimination.

Genomic resources and technology development have the potential to greatly contribute to the renewed malaria elimination effort through enhanced biological and epidemiological understanding. Recent work from the Broad GCID and other groups has illustrated the power of malaria genomic epidemiology for practical applications such as:

• understanding the impact of interventions on parasite or vector population size and evolution,

• profiling the connectivity of parasite and vector populations

• Distinguishing locally transmitted vs. imported malaria infections

The GCID has also shown that parasite population genomic signals can identify parasite genetic loci associated with adaptation to different mosquito vector species. This project is extending these advances significantly in both the parasite and vector realm, and developing crucial communal resources to support New World vector and parasite genomics through the following four aims.

Aims:

1. To develop a major population genomic resource for neotropical (Central/South American, Caribbean) anopheline malaria vectors.

2. To profile the population genomics of malaria parasites across the Neotropics.

3. To identify parasite genes that mediate interactions with mosquito vectors by sequencing parasites from diverse naturally-infected sympatric vector species inGabon.

4. To define the transcriptional profile of Plasmodium parasites during under-characterized pre-erythrocytic developmental stages.

This work will influence the field through the generation of novel genomic resources and methods, new biological insights, and innovative analytical methods, and will push the malaria genomics forward in both genomic data generation and interpretation capabilities to inform basic biological studies, as well as disease intervention efforts.

GCID scientists conduct additional work on parasite and vector genomics through the Broad Institute's Infectious Disease and Microbiome Program.