Cyrille BOTTÉ

Information

Scientific interests and projects

The research team I currently lead (https://twitter.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. Yang L, Uboldi AD, Seizova S, Wilde ML, Coffey MJ, Katris NJ, Yamaryo-Botté Y, Kocan M, Bathgate RAD, Stewart RJ, McConville MJ, Thompson PE, Botté CY, Tonkin CJ. An apically located hybrid guanylate cyclase-ATPase is critical for the initiation of Ca2+ signaling and motility in Toxoplasma gondii. J Biol Chem. 2019 May 31;294(22):8959-8972. doi: 10.1074/jbc.RA118.005491.

2. Uboldi AD, Wilde ML, McRae EA, Stewart RJ, Dagley LF, Yang L, Katris NJ, Hapuarachchi SV, Coffey MJ, Lehane AM, Botte CY, Waller RF, Webb AI, McConville MJ, Tonkin CJ. Protein kinase A negatively regulates Ca2+ signalling in Toxoplasma gondii. PLoS Biol. 2018 Sep 12;16(9):e2005642. doi: 10.1371/journal.pbio.2005642.

3. Dubois D, Fernandes S, Amiar S, Dass S, Katris NJ, Botté CY, Yamaryo-Botté Y. Toxoplasma gondii acetyl-CoA synthetase is involved in fatty acid elongation (of long fatty acid chains) during tachyzoite life stages. J Lipid Res 2018 Apr 20;59(6):994–1004. doi: 10.1194/jlr.M082891

4. Sindikubwabo F, Ding S, Hussain T, Ortet P, Barakat M, Baumgarten S, Cannella D, Palencia A, Bougdour A, Belmudes L, Couté Y, Tardieux I, Botté CY, Scherf A, Hakimi MA. Modifications at K31 on the lateral surface of histone H4 contribute to genome structure and expression in apicomplexan parasites. Elife. 2017 Nov 4;6:e29391. doi: 10.7554/eLife.29391.

5. Lévêque MF, Berry L, Yamaryo-Botté Y, Nguyen HM, Galera M, Botté CY, Besteiro S. TgPL2, a patatin-like phospholipase domain-containing protein, is involved in the maintenance of apicoplast lipids homeostasis in Toxoplasma. Mol Microbiol. 2017 Jul;105(1):158-174. doi: 10.1111/mmi.13694.