Identifying key amino acid metabolic steps as potential drug targets for Chagas disease treatment

Chagas disease affects millions of people in Latin America and is concentrated amongst the marginalized poor. The causal agent is Trypanosoma cruzi which is transmitted between humans by an insect vector. The movement between insect and human represents a drastic environmental change for the trypanosome including huge differences in nutrient availability. In this context, the metabolism of amino acids is part of an intricate metabolic network necessary for trypanosome proliferation. I aim to identify essential steps in the amino acid metabolism by systematically knocking out the genes for 40 steps in the network and analyzing the effect on the ability to cause infection. Each of the knockout cell lines will be marked with a unique DNA barcode and relative fitness during cell differentiation, transmission and infection will be measured. Using this approach, I will identify the enzymes that are essential for infection and thus novel potential targets for drug design.