Defining the genetic signature of malaria transmission
Malaria is a global health threat with more than 200 million cases and 400’000 deaths each year, most of them cause by Plasmodium falciparum. The goal of this project entitled “Functional analysis of natural drivers for transmission in malaria” is to define and functionally validate genetic determinants of malaria transmission. We hypothesize that the parasite’s ability to adapt to short- and long-term variation in environmental conditions (between individual hosts, across geographic regions and species) is determined by a combination of genetic and epigenetic factors. Recent work by the PIs has identified genetic loci linked to transmission that are under strong diversifying selection in P. falciparum, and lineage-specific expansion or loss of other loci across the Plasmodium genus. In addition, the PIs have spearheaded development and implementation of single cell OMICs, and novel computational methods to process NGS data. Here we propose the following approaches to systematically mine available datasets: i) Identify signatures of diversifying selection driving variation in transmission rates across P. falciparum strains, and ii) identify lineage-specific changes over evolutionary scales related to transmission across Plasmodium lineages. Second, we will functionally investigate these loci using reverse genetics in P. falciparum and the rodent parasite P. berghei.
Co-PI: Dr. Thomas Otto.
References:
1. Brancucci NMB, et al. (2017) Cell 171:1.
2. Rutledge GG, et al. (2017) Nature 542(7639):101.