ApicoLipid: Comprehensive analysis of apicoplast lipid metabolism and biogenesis of Apicomplexa parasites – ApicoLipid

Apicomplexan-caused diseases, especially malaria, represent a massive social and economic burden, against which there is no current vaccine. A limited series of drugs have been developed in the last half-century, but the parasites have developed resistance to all marketed molecules, including most recent front-line drug artemisinin, making most drugs virtually useless. Therefore, there is a pressing need for the development of new efficient molecules.
In the late 90s, a major breakthrough was reached with the discovery that Apicomplexa harbour a non-photosynthetic relict plastid, the apicoplast. The apicoplast has been acquired by a secondary endosymbiosis of a unicellular red algae. Its origin has recently been confirmed by the discovery of Chromera velia, an Apicomplexa relative retaining a photosynthetic apicoplast. Importantly, the apicoplast harbours vital metabolic pathways for the parasite, thus revealing a major new set of drug targets of plant/algal origin. Although bioinformatic and biochemical approaches have provided great insights into a previously unrecognised lipid metabolism, it is unclear why parasites are dependent on their apicoplasts and how its metabolic pathways are required under specific cellular context and life cycle. Understanding this dependency can be explained by determining the role of apicoplast (glycero)lipid products. Major questions remain unanswered: What lipids are synthesized by the apicoplast biosynthetic machineries? Are these lipids needed for the apicoplast biogenesis or are they exported to other membrane compartments?If exported, what are their fate and how are they trafficked? The proposed Apicolipid project aims to address some of these questions. The results will highlight the apicoplast’s precise functions. It will also help characterizing new potential drug targets. Our investigation goes beyond understanding the apicoplast metabolism and seeks to establish its raison d’être.