Study of cytoplasmic crowding during antifungal drug tolerance

The candidate will take advantage of a live-cell microscopy method, that has been recently established in Candida albicans, to quantitate cytoplasmic crowding in this opportunistic human pathogenic fungus, using a variety of molecular and cellular approaches. Main activities A 3-year PhD fellowship is available in the Polarized growth in yeast group at the Institute of Biology Valrose (iBV) at the University of Côte d’Azur in Nice, FR (http://ibv.unice.fr/research-team/arkowitz/). Our team studies the spatial and temporal regulation of filamentous growth using a range of state-of-the art microscopy approaches. Drug tolerance is generally described as microbe survival or growth above inhibitory concentrations and subpopulations of C. albicans can grow above minimal inhibitory drug concentrations. Tolerance, i.e. slow growth in presence of drug, is dependent on cell stress response pathways. Cytoplasmic crowding is intimately tied to protein abundance, and hence affected by stresses such as starvation, which are activated via amino acid sensing, and also likely to affect drug tolerance. The goal of this collaborative project is to determine the link between antifungal drug tolerance and cytoplasmic crowding at the single cell level. The project will take advantage of cutting-edge imaging approaches, molecular genetics and image analyses to investigate relationship between physical characteristics of the cytoplasm and antifungal tolerance in C. albicans cells and communities. Objectives: -Determine the heterogeneity of cytoplasmic crowding in a population of cells and whether it correlates with an antifungal drug tolerance. -Determine the link between intracellular antifungal drug concentration and cytoplasmic crowding. -Quantify cytoplasmic crowding in a range of stress response mutants and clinical isolates. Candidates should have a Master’s degree or equivalent in a relevant field. We are seeking highly motivated candidates with a background in Cell Biology, Microbiology, Microscopy or Biophysics – previous experience in live cell imaging and/or image analyses is a plus. Motivation, enthusiasm, ability to communicate in English and interact with lab members are critical and applicants are encouraged to apply and contact Robert Arkowitz (arkowitz@unice.fr). Selected publications: 1. R. Abdul-Ganiyu, L. A. Venegas, X. Wang, C. Puerner, R. A. Arkowitz, B. K. Kay & D. E. Stone. Sci Signal, in press. 2. C. Puerner, N, Kukhaleishvili, D. Thomson, S. Schaub, X. Noblin, S. Seminara, M. Bassilana & R. A. Arkowitz. BMC Biol. 2020 18: 122. Actualité scientifique CNRS INSB: https://insb.cnrs.fr/fr/cnrsinfo/confinement-force-biophysique-de-linvasion-fongique 3. M. Bassilana, C. Puerner & R. A. Arkowitz. Curr Op Cell Biol. 2020 62:150. 4. R. A. Arkowitz & Bassilana M. F1000 Res. 2019 8. 5. P. M. Silva, C. Puerner, A. Seminara, M. Bassilana & R. A. Arkowitz. Cell Rep. 2019 28: 2231. Actualité scientifique CNRS INSB: https://insb.cnrs.fr/fr/cnrsinfo/reinitialiser-la-polarite-cellulaire-sousleffet-de-la-lumiere 6. A. Weiner, F. Orange, S. Lacas-Gervais, K. Rechav, V. Ghugtyal, M. Bassilana & R. A. Arkowitz. Cell Microbiol. 2019 21: e12963. Selected by Faculty 1000 December 18, 2018. https://f1000.com/prime/734234273?bd=1&ui=206550 7. H. Labbaoui, S. Bogliolo, V. Ghugtyal, N. V. Solis, S. G. Filler, R. A. Arkowitz & M. Bassilana. PLoS Pathogens. 2017 13: e1006205. 8. V. Ghugtyal, R. Garcia-Rodas, A. Seminara, S. Schaub, M. Bassilana & R. A. Arkowitz. PNAS USA. 2015 112: 8644. 9. S. G. Martin & R. A. Arkowitz. FEMS Microbiol Rev. 2014 38: 228. 10. V. Corvest, S. Bogliolo, P. Follette, R. A. Arkowitz & M. Bassilana. Mol Microbiol. 2013 89: 626. 11. A. Vernay, S. Schaub, I. Guillas, M. Bassilana & R. A. Arkowitz. J Cell Biol. 2012 198: 711. Selected by Faculty 1000 March 19, 2013. http://f1000.com/prime/717988257. Context The Valrose Institute of Biology (28 teams; 300 people; 25 nationalities) is an international institute (English is the working language) with a very rich scientific environment. The iBV provides cutting-edge technological infrastructures and platforms, with a collaborative and lively atmosphere in a very attractive city / region (ibv.unice.fr). Skills/experience – An experience with fungal cells is a plus but is not necessary. – Experience in microscopy. – Sense of initiative and ability to work independently. – Ability to work in a team and to communicate. – Ability to carry out careful controlled and rigorous experiments. – Sense of organization and autonomy. – Ease of communication in written and oral English.