Équipe : Croissance polarisée chez la levure / Polarized growth in yeast
Responsable : Robert Arkowitz
Laboratoire : UMR 7277 Insitut de Biologie Valrose (Nice)
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Descriptif :
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 TRAFIC -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.
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 TRAFIC -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.
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