ARKOWITZ

Robert ARKOWITZ

Polarized growth in yeast

Main interests

  • Transduction of external stimuli into asymmetric growth that is tightly controlled in time and space
  • Coordination and regulation of membrane traffic resulting in distinct cell shape changes
  • Temporal and spatial regulation of forces involved in invasive growth
  • Interplay between force generation, cell polarity/cell organization and membrane traffic

Scientific Questions

Our main interest is how cells spatially and temporally regulate growth. Polarized growth is essential for both internal organization and generation of complex multi-cellular structures. Asymmetric growth requires the specification of a polarity site, orientation of the cytoskeleton towards this site and subsequent directed membrane traffic. Our primary focus is on polarized growth, morphogenesis and development in response to external cues, predominantly in the human pathogenic yeast Candida albicans but also in the baker’s yeast Saccharomyces cerevisiae. The human commensal C. albicans switches from an oval yeast form to a hyphal filamentous form that can invade tissue and evade host immune cells. This dimorphic switch is critical for pathogenicity of C. albicans, which is a major cause of life-threatening nosocomial infections as well as persistent mucosal infections. We are investigating the roles of polarity, membrane traffic and mechanical forces in this human fungal pathogen.

Our Strategy

We take advantage of a range of genetic and chemical perturbations to probe cell polarity, membrane traffic and invasive growth in C. albicans. Molecular genetic approaches are used to generate mutants and fluorescent reporter fusions. A variety of microscopy techniques are used to probe the dynamics of cell polarity, membrane traffic and invasive growth with high temporal and spatial resolution. An assortment of reporters for lipid and active small GTPase distribution are optimized and used to follow establishment and maintenance of cellular asymmetries in vivo. In addition, micro-fabrication approaches are used to impose and vary physical constraints in these studies. We also work in close collaboration physicists to model aspects of cell polarity, membrane traffic and invasive growth in order to predict key parameters in these processes that will be subsequently tested.

Research Aims

Polarity

  • Role of GTPases and lipids in initiation and maintenance of asymmetric growth.
  • Cellular reorganization upon cell shape changes.
  • Importance of cell polarity in multicellular structures.
  • Regulation of cell polarity upon external stimuli or changes in the environment, including host cells.
  • Role of cell polarity in force generation and regulation of membrane traffic.

Membrane traffic

  • Regulation of membrane traffic during yeast to hyphal transition.
  • Membrane traffic dynamics during invasion and infection.
  • Coordination of membrane traffic in multicellular structures.
  • Traffic and transport of membrane lipids and their importance in hyphal growth.
  • Local control of membrane traffic for site-specific growth and cell shape changes.

Forces

  • Forces critical for invasive growth.
  • Effect of resistive forces on cellular organization and polarity.
  • Role of local alterations or perturbations of resistive and cellular forces during substrate penetration and invasion.
  • Importance of membrane traffic and cell wall for invasive growth.
  • Cellular forces and interplay with resistive forces during different types of infection.
Researchers

BASSILANA Martine
FOLLETTE Peter

Postdocs

WEINER Allon

PreDocs

BASANTE BEDOYA Miguel Angel
DE OLIVEIRA E SILVA Patricia Maria
KUKHALEISHVILI Nino
LABBAOUI Hayet
PUERNER Charles

Engineers & Technicians

BOGLIOLO Stéphanie

 

Recent publications

  1. Bar-Yosef, H, Gildor, T, Ramírez-Zavala, B, Schmauch, C, Weissman, Z, Pinsky, M et al.. A Global Analysis of Kinase Function in Candida albicans Hyphal Morphogenesis Reveals a Role for the Endocytosis Regulator Akl1. Front Cell Infect Microbiol. 2018;8 :17. doi: 10.3389/fcimb.2018.00017. PubMed PMID:29473018 PubMed Central PMC5809406.
  2. Wakade, R, Labbaoui, H, Stalder, D, Arkowitz, RA, Bassilana, M. Overexpression of YPT6 restores invasive filamentous growth and secretory vesicle clustering in a Candida albicans arl1 mutant. Small GTPases. 2017; :1-7. doi: 10.1080/21541248.2017.1378157. PubMed PMID:28960163 .
  3. Labbaoui, H, Bogliolo, S, Ghugtyal, V, Solis, NV, Filler, SG, Arkowitz, RA et al.. Role of Arf GTPases in fungal morphogenesis and virulence. PLoS Pathog. 2017;13 (2):e1006205. doi: 10.1371/journal.ppat.1006205. PubMed PMID:28192532 PubMed Central PMC5325608.
  4. Lin, TC, Neuner, A, Flemming, D, Liu, P, Chinen, T, Jäkle, U et al.. MOZART1 and γ-tubulin complex receptors are both required to turn γ-TuSC into an active microtubule nucleation template. J. Cell Biol. 2016;215 (6):823-840. doi: 10.1083/jcb.201606092. PubMed PMID:27920216 PubMed Central PMC5166503.
  5. Stone, DE, Arkowitz, RA. In Situ Assays of Chemotropism During Yeast Mating. Methods Mol. Biol. 2016;1407 :1-12. doi: 10.1007/978-1-4939-3480-5_1. PubMed PMID:27271890 .
  6. Ismael, A, Tian, W, Waszczak, N, Wang, X, Cao, Y, Suchkov, D et al.. Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation. Sci Signal. 2016;9 (423):ra38. doi: 10.1126/scisignal.aad4376. PubMed PMID:27072657 PubMed Central PMC4908976.
  7. Ghugtyal, V, Garcia-Rodas, R, Seminara, A, Schaub, S, Bassilana, M, Arkowitz, RA et al.. Phosphatidylinositol-4-phosphate-dependent membrane traffic is critical for fungal filamentous growth. Proc. Natl. Acad. Sci. U.S.A. 2015;112 (28):8644-9. doi: 10.1073/pnas.1504259112. PubMed PMID:26124136 PubMed Central PMC4507248.
  8. Arkowitz, RA, Bassilana, M. Rho GTPase-phosphatidylinositol phosphate interplay in fungal cell polarity. Biochem. Soc. Trans. 2014;42 (1):206-11. doi: 10.1042/BST20130226. PubMed PMID:24450653 .
  9. Martin, SG, Arkowitz, RA. Cell polarization in budding and fission yeasts. FEMS Microbiol. Rev. 2014;38 (2):228-53. doi: 10.1111/1574-6976.12055. PubMed PMID:24354645 .
  10. Ramírez-Zavala, B, Weyler, M, Gildor, T, Schmauch, C, Kornitzer, D, Arkowitz, R et al.. Activation of the Cph1-dependent MAP kinase signaling pathway induces white-opaque switching in Candida albicans. PLoS Pathog. 2013;9 (10):e1003696. doi: 10.1371/journal.ppat.1003696. PubMed PMID:24130492 PubMed Central PMC3795047.
  11. Corvest, V, Bogliolo, S, Follette, P, Arkowitz, RA, Bassilana, M. Spatiotemporal regulation of Rho1 and Cdc42 activity during Candida albicans filamentous growth. Mol. Microbiol. 2013;89 (4):626-48. doi: 10.1111/mmi.12302. PubMed PMID:23796158 .
  12. Guillas, I, Vernay, A, Vitagliano, JJ, Arkowitz, RA. Phosphatidylinositol 4,5-bisphosphate is required for invasive growth in Saccharomyces cerevisiae. J. Cell. Sci. 2013;126 (Pt 16):3602-14. doi: 10.1242/jcs.122606. PubMed PMID:23781030 .
  13. Deflorio, R, Brett, ME, Waszczak, N, Apollinari, E, Metodiev, MV, Dubrovskyi, O et al.. Phosphorylation of Gβ is crucial for efficient chemotropism in yeast. J. Cell. Sci. 2013;126 (Pt 14):2997-3009. doi: 10.1242/jcs.112797. PubMed PMID:23613469 .
  14. Arkowitz, RA. Cell polarity: wanderful exploration in yeast sex. Curr. Biol. 2013;23 (1):R10-2. doi: 10.1016/j.cub.2012.11.037. PubMed PMID:23305660 .
  15. Vernay, A, Schaub, S, Guillas, I, Bassilana, M, Arkowitz, RA. A steep phosphoinositide bis-phosphate gradient forms during fungal filamentous growth. J. Cell Biol. 2012;198 (4):711-30. doi: 10.1083/jcb.201203099. PubMed PMID:22891265 PubMed Central PMC3514036.
  16. Arkowitz, RA. Polarized growth and movement: how to generate new shapes and structures. Semin. Cell Dev. Biol. 2011;22 (8):789. doi: 10.1016/j.semcdb.2011.10.001. PubMed PMID:22001109 .
  17. Arkowitz, RA, Bassilana, M. Polarized growth in fungi: symmetry breaking and hyphal formation. Semin. Cell Dev. Biol. 2011;22 (8):806-15. doi: 10.1016/j.semcdb.2011.08.010. PubMed PMID:21906692 .
  18. Vauchelles, R, Stalder, D, Botton, T, Arkowitz, RA, Bassilana, M. Rac1 dynamics in the human opportunistic fungal pathogen Candida albicans. PLoS ONE. 2010;5 (10):e15400. doi: 10.1371/journal.pone.0015400. PubMed PMID:21060846 PubMed Central PMC2965673.
  19. Hope, H, Schmauch, C, Arkowitz, RA, Bassilana, M. The Candida albicans ELMO homologue functions together with Rac1 and Dck1, upstream of the MAP Kinase Cek1, in invasive filamentous growth. Mol. Microbiol. 2010;76 (6):1572-90. doi: 10.1111/j.1365-2958.2010.07186.x. PubMed PMID:20444104 .
  20. Suchkov, DV, DeFlorio, R, Draper, E, Ismael, A, Sukumar, M, Arkowitz, R et al.. Polarization of the yeast pheromone receptor requires its internalization but not actin-dependent secretion. Mol. Biol. Cell. 2010;21 (10):1737-52. doi: 10.1091/mbc.e09-08-0706. PubMed PMID:20335504 PubMed Central PMC2869379.
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2015 - Marie Curie Multi-ITN (H2020-MSCA-ITN-2015)

2013 - Marie Curie Multi-ITN (FP7-PEOPLE-2013-ITN)

2012 - France Berkeley Fund Award

2005 - Marie Curie Host Fellowships for Early Stage Researchers (EST). FP6-2002-Mobility 2

2002 - Equipe Labellisée - La Ligue Contre le Cancer

2001 - Young Investigator Programme - EMBO

2001 - France Berkeley Fund Award

2001 - FRM Fondation pour la Recherche Médicale – BNP Paribas Award

2000 - Installation Award - FRM

2000 - ATIP - CNRS

1998 - EU Eurofan II (European Network for the Functional Analysis of Yeast Genes) FP5

iBV - Institut de Biologie Valrose

"Centre de Biochimie"

Université Nice Sophia Antipolis
Faculté des Sciences
Parc Valrose
06108 Nice cedex 2