National Institute of Blood Transfusion & INSERM

Start : July 2015 | Status : Active

The scientist: Julien Duez will focus his research on the discovery of new drugs against Plasmodium falciparum, through a project titled "BlockBackMalaria”. The objective is to block early asexual stages (rings) and mature sexual stages (stage 5 gametocytes) in the spleen to cure clinical attacks and interrupt transmission. Julien is a Postdoctoral Researcher affiliated to National Institute for Blood Transfusion (INTS) and INSERM in Paris, under the mentorship of Pierre Buffet, PI of the project. Julien is specialized in biology-medicinal chemistry, with a 3-year experience in malaria drug screening. Another post-doctoral student and an experienced graduate investigator will soon join the team.

The sponsors: The French National Institute for Blood Transfusion (INTS) is a public benefit corporation hosting scientific, training and reference activities in a bid to improve transfusion safety and optimize transfusion practices. At INTS, the team works on erythrocyte biomechanics under normal or physiopathological conditions (ie. malaria or transfusion) in relation to human spleen filtering properties.

Founded in 1964, the French National Institute of Health and Medical Research (Inserm) is a public scientific and technological institute which operates under the joint authority of the French Ministry of Health and French Ministry of Research. Inserm has forged close partnerships with others public and private research establishments, such as INTS.

Foundation funding: The Foundation is providing £99,120 in support.

GSK’s contribution: 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.

Project Description: 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.