The malaria chemical atlas: Revealing the parasite-host functional interactome (MalChemAtlas)

Malaria is the most life-threatening parasitic disease in humans. Invasion of the malaria parasite, Plasmodium falciparum (Pf), into the blood circulation rewires the harmonious networking between the resident cells. Until recently, Pf was not thought to be able to communicate when nested within infected human red blood cells (RBCs). However, the foundations of Pf communication via extracellular vesicles have been laid now. The hypothesis now is that in order to survive in the hostile host environment, Pf secretes chemical inducers (e.g., metabolites, peptides) to actively coordinate life decisions as a group and to control the surrounding host cells. Remarkably, proof-of-principle preliminary results were obtained in the form of an isolated, active chemical fraction that inhibits Pf population growth in a density-dependent manner. The overarching goal in MalChemAtlas is to expose this yet-to-be-revealed mode of communication in malaria: cell-to-cell chemical signaling. In this effort, the extensive (HPLC-based) analytical fractionation pipeline, combined with NMR and metabolomics analyses will be leveraged for identifying malaria-secreted autoinducers. Preliminary findings demonstrate the potential of our basic research to be applied to the translational level of intervention. Identifying “natural chemical killers” offers a previously unexplored direct strategy to fight malaria – the highest gain we can ask for when researching this deadly disease.

Project details

Basic Science
Enabling Technologies & Assays

Oct 2023 — Sep 2028

$2.16M

Israel