Cyrille BOTTÉ

Information

Scientific interests and projects

The research team I currently lead (https://NotAllowedScript6744ac5b26699twitter.com/ApicoLipid @ApicoLipid) as CNRS Research Director focuses on understanding how Apicomplexan parasites acquire lipids and nutrient essential for their propagation and survival within their host cells.

Apicomplexa are unicellular eukaryotes and pathogenic agents responsible for major human diseases such as 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. The renewal of our therapeutic arsenal needed for the eradication of these diseases depends on deciphering metabolic pathways that sustain parasite survival within the host and its environment.

Current evidences all point at lipid synthesis and membrane biogenesis as crucial pathways for parasite intracellular development.

Major biological questions remain and focus our current attention (i) how are lipids acquired, remodelled and trafficked from the host cell to the parasite and between parasite intracellular compartments? (ii) what is the input of scavenged vs de novo synthesised lipids? (iii) what are the mechanisms of lipid fluxing and trafficking from these two pathways? (iv) how does parasites sense and regulate these pathways to adapt to physiological changes of host nutritional and environmental conditions? (v) what are the parasite lipid signals required for intracellular development?

Our laboratory have set up major facilities and equipements that includes a P3* cell culture facility (MESRI-HCB), and a fully independent lipidomic-fluxomic platform encompassed within our P3* (http://gemeli-uga.fr/GEMELI.html), both parts of the core facilities of our Institution at the Université Grenoble Alpes. Our robust expertise and facilities thus allows us to conduct large metabolomics and lipidomics analyses beyond our central scope, on infectious diseases and other models, to determine metabolic signatures or monitoring metabolite fluxes. We currently lead major collaborative projects with national and international partners (LIA University Melbourne/WEHI, CEFIPRA ICGEB New Dehli…).

Top 5 publications of the last 5 years

1. Amiar S, Katris NJ, Berry L, Dass S, Shears MJ, Brunet C, Touquet B, McFadden GI, Yamaryo-Botté Y*, Botté CY*. (2019) Division and adaptation to host nutritional environment of apicomplexan parasites depend on apicoplast lipid metabolic plasticity and host organelles remodelling, Accepted in Cell Reports, (CELL-REPORTS-D-19-01152)

2. Dubois D, Fernandes S, Amiar S, Dass S, Katris NJ, Botté CY*, Yamaryo-Botté Y*. (2018)(*colast and corresponding) Toxoplasma gondii acetyl-CoA synthetase is involved in fatty acid elongation (of long fatty acid chains) during tachyzoite life stages. J Lipid Res. 59(6):994-1004

3. Shears MJ, MacRae JI, Goodman DG, Mollard VSU, Botté CY *, McFadden GI*. (2017) (*co-last) Characterization of the Plasmodium falciparum and P. berghei glycerol-3-phosphate acyltranferase involved in FASII fatty acid utilization in the malaria parasite apicoplast. Cellular Microbiology 19(1)

4. Amiar S, MacRae JI, Callahan DL, vanDooren GG, Shears MJ, Dubois D, Cesbron-Delauw MF, Maréchal E, McConville MJ, McFadden GI, Yamaryo-Botté Y*, Botté CY *. (2016) The Toxoplasma gondii apicoplast is responsible for bulk phospholipid synthesis mainly via a plantlike glycerol 3-phosphate acyltransferase for lysophosphatidic acid precursor assembly. Plos Pathogens 4;12(8):e1005765

5. Bullen H+, Jia Y+, Yamaryo-Botté Y, Klages J, Carruthers V, Botté CY, Soldati-Favre D. (2016) . Phosphatidic acid-mediated signaling is essential for microneme secretion in Toxoplasma. Cell Host and Microbe 9;19(3):349-60