Investigating susceptibility to trypanosomatid parasites using drosophila melanogaster as a model
One of the specific United Nations Sustainable Development goals is to end epidemics of neglected tropical diseases by year 2030. Some of the most devastating of these diseases are caused by trypanosomatid parasites that are transmitted to humans via the bites of infected insects from the order Diptera (Flies). While most natural fly vectors pose a challenge to study under laboratory conditions, Drosophila melanogaster, with its well-established molecular, genetic and genomic toolkit and a vast amount of prior knowledge of its biology, is a proven model for experimental studies. Because D. melanogaster is host to several natural parasites that belong to the trypanosomatid group, it can also serve as a model for studying fly-parasite interactions. In this project, we propose to take advantage of the Drosophila melanogaster Genetic Reference Panel (DGRP) to investigate the genetic basis of fly susceptibility to trypanosomatid infection. First, we will perform a genome-wide association study (GWAS) for natural susceptibility to trypanosomatid parasite using a well-developed DGRP mapping resource to map genetic variation in susceptibility. Further, we will also test for differences in gene expression associated with infection susceptibility, using RNA sequencing, and validate the candidate genes identified with GWAS and RNA sequencing. Together, along with the well-annotated Drosophila genome, these data will reveal functional pathways affecting susceptibility to trypanosomatid infection. The established Drosophila-trypanosomatid system can serve as a functional model for insect-vectored diseases in medically and economically relevant species of Diptera.