Cyrille BottéInstitut pour l'Avancée des Biosciences (IAB) - CNRS / Inserm / Université Grenoble Alpes

Mes recherches

The research team I currently lead (https://twitter.com/ApicoLipid @ApicoLipid) as CNRS Research Director focuses on understanding how Apicomplexan parasites (intracellular human pathogens responsible for malaria and toxoplasmosis) acquire lipids and nutrient essential for their propagation and survival within their host cells. I initially obtained my PhD in 2007 at the Université Grenoble Alpes/CEA Grenoble under the supervision of Dr Eric Maréchal. My project focused on the characterization of plant-like lipid synthesis as drug target against plants and apicomplexans. I then coordinated a FP7 Marie Curie Actions project (2008-2011) articulated between with the team of Prof Geoff McFadden at the University of Melbourne (Australia) and the Université Grenoble Alpes to perform the first isolation and lipidomic analysis of the non-photosynthetic plastid (apicoplast) of the malaria parasite. I was recruited as CR2 CNRS in 2013 and set up my research team “Lipid synthesis and membrane biogenesis in malaria and toxoplasmosis” at the Institute for Advanced Biosciences (CNRS UMR5309 INSERM U1209 Université Grenoble Alpes) under the financial support of ATIP-Avenir. We developed a strong expertise in parasite lipid analysis, lipidomic and fluxomic analysis, which allowed us to answer major questions in the parasite metabolic interactions with its human host. We have set up major facilities and equipements within our facilities, such as a P3* cell culture facility, and a fully independent lipidomic-fluxomic platform that are both part of the core facilities of our Institution and the Université Grenoble Alpes (http://gemeli-uga.fr/GEMELI.html). This expertise and facilities has allowed us to currently extend into a larger metabolomic-lipidomic platform dedicated to health, which activity spans beyond our initial scope (infections, cancer, metabolic signature…) and develop national and international collaboration (LIA Uni Melbourne, CEFIPRA). Our team, which is part of the national labex Parafrap (https://labex-parafrap.fr/en/labex-parafrap) currently focuses on the metabolic pathways allowing membrane biogenesis, lipid synthesis/trafficking/signalling between, nutrient acquisition and host-parasite metabolic interactions and adaptation.

The role of the non-photosynthetic plastid of apicomplexan parasites for lipid synthesis and parasite survival

APICOLIPID

Apicomplexa are unicellular eukaryotes and pathogenic agents responsible for major human diseases such as (i) Toxoplasmosis, major chronic disease affecting ~1/3 of the world population and a lethal threat to immunocompromised patients, and (ii) malaria affecting 250 millions people/year, killing ~1/2million/year, mainly children. Throughout their life cycle, Apicomplexa parasites require large amount of lipids for parasite survival and pathogenesis. Apicomplexa were long thought incapable for de novo lipid synthesis, solely relying on their host to supply them. However, the striking discovery of non-photosynthetic chloroplast, i.e. the apicoplast, in apicomplexans, and its prokaryotic type II fatty acid synthesis pathway challenged this dogma, suggesting that parasites could also be capable of synthesizing their own lipids using plant-like pathways to meet the demand in lipids required for parasite survival. Since this discovery, major questions remained to be answered: What lipids are synthesized by the apicoplast biosynthetic machineries and which ones are acquired from the host? What is the role for each lipid source in parasite survival? If lipids are exported from the apicoplast, what is their final destination, for what use and how are they trafficked outside the organelle? Throughout our Atip-Avenir project, our team aimed to address these important questions in both T. gondii, and P. falciparum.