Principal Investigator (PI)
The French National Institute for Blood Transfusion (INTS)
The Foundation is providing £92,120 in support.
Mario Carucci - Julien Duez
GSK will allocate in-kind contribution to the project, including scientific expertise in malaria and HTS screenings as well as access to the GSK´s collection of compounds.
This proposal is a continuation of a project funded by the Bill & Melinda Gates Foundation. The project team has established a screening and post-screening process based on a filtration device that replicates the mechanical sensing of circulating red blood cells (RBC) by the human spleen. Active compounds are expected to stiffen and induce the mechanical retention of Plasmodium falciparum-infected RBC in the spleen, thereby triggering their rapid clearance from the circulation. Using the RBC filtration system adapted to microplates, a candidate compound (calyculin) has been shown to induce the mechanical retention of 80-90% of mature gametocytes at concentrations lower than those affecting their viability. Calyculin-stiffened mature gametocytes were also held into spleno-mimetic microfluidic chips and were cleared from the circulation of macrophage depleted mice as rapidly as heat-stiffened control uninfected RBC, validating the outcomes of the microsphiltration assay.This project will extend the screening to asexual stages (circulating rings) and increase throughput to screen larger libraries on blood stages and mature gametocytes.