Sophie Martin, SNF Professor
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Sophie Martin earned her Diploma in 1999 from the UNIL for her study of chromatin organization in the laboratory of Dr Susan Gasser at the Swiss Institute for Experimental Cancer Research (ISREC). She then joined the group of Dr Daniel St Johnston at the Wellcome/CR UK Gurdon Institute to study the molecular mechanisms of cell polarization and mRNA localization using Drosophila as model system and received her PhD in 2003 from the University of Cambridge. She obtained postdoctoral training in the laboratory of Dr Fred Chang at Columbia University in New York, studying cell polarization and the cytoskeleton in the fission yeast. She joined the CIG as a Swiss National Science Foundation Professor in September 2007. In 2009, she was elected as an EMBO *** Space is available for postdoctoral researchers and/or PhD students who can attract their own funding. *** Keywords: cell polarity, cytoskeleton, actin, microtubules, cell cycle, cancer, fission yeast Schizosaccharomyces pombe
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Research Summary
Molecular mechanisms of cell polarization
Polarity is crucial for cell function both during development and in differentiated cells. Cell polarity underlies the asymmetric division of stem cells to generate cell diversity and the function of differentiated cells, such as neurons, epithelial or immune cells. In proliferating cells, cell polarization is tightly linked with cell cycle controls. Indeed, loss of cell polarity has been associated not only with diseases affecting specific tissues or organs, but also with cancer, where it may contribute to uncontrolled proliferation. Thus understanding how a cell acquires and maintains polarity is a fundamental question in cell biology.
Our research aims to address how a cell acquires and maintains cell polarity and how this process is linked with cell proliferation. We use the fission yeast, Schizosaccharomyces pombe, as model system because it affords powerful genetic, biochemical and live-cell imaging tools. Fission yeast has a very small genome, encoding about 5000 genes, two thirds of which show direct homology with mammalian genes. This organism has been successfully used over the last 30 years to unravel fundamental mechanisms of cell proliferation and morphogenesis. We focus on three major areas of research:
Microtubule -dependent cell polarization
The cytoskeleton – microtubules and actin filaments – is essential for cell polarization. In rod-shaped fission yeast cells, microtubules are organized in a dynamic network aligned with the length of the cell and serve to transport polarity determinants towards the extremities of the cell. Microtubules provide positional information for growth at cell extremities and cells with anomalies in their microtubule network grow at ectopic locations. The actin cytoskeleton is organized at the cell extremities and essential for polarized growth. We had previously demonstrated that a microtubule-associated protein, tea4p, binds an actin nucleator of the formin family, for3p, thereby directly linking positional information provided by microtubules to actin assembly. We have now generated point mutations in tea4p to investigate its mode of localization and regulation. Our ongoing investigations suggest that tea4p may integrate phosphorylation and de-phosphorylation events to control cell polarization.
Formin -dependent cell polarization
Formins are key actin organizers that nucleate linear actin filaments. Formins are essential for cell polarization in vegetative cells as they assemble a polarized network of actin cables that allows the delivery of myosin-driven cargoes to sites of polarized cell growth. These cargoes include membrane material and cell wall remodeling components essential for polarized cell growth. Yeast cells also show prominent polarization during the mating process, when two cells of opposite mating type extend cellular projections towards each other. We are currently investigating formin regulation during polarized cell growth.
Connections between polarization and proliferation
Cell polarization is intimately linked to cell cycle changes. For instance, it has been proposed that loss of cell polarity influences cell proliferation and contributes to tumour formation. We have focused our investigations on a well-studied regulator of cell morphogenesis, the DYRK kinase pom1p, and uncovered a novel function for pom1p as an inhibitor of cell cycle progression. Pom1p forms gradients from cell ends. As cells grow in length during interphase, the pom1p gradients get further apart, lowering the concentration of pom1p at the cell middle in longer cells. We found that pom1p negatively regulates the SAD kinase cdr2p, a cell cycle activator itself localized at the cell equator throughout interphase. Our data suggest a model in which overlap between pom1p and cdr2p at the middle of short cells leads to mitotic delay while pom1p levels are no longer sufficient at the middle of long cells to inhibit cdr2p, thus allowing entry into mitosis. Gradients of pom1p thus provide a novel cell-intrinsic measure of cell length to ensure that sufficient length is attained before division. The high conservation of cell cycle regulators and cell polarization mechanisms across evolution suggests that lessons learned from yeast will be applicable to mammalian cells.
Representative Publications
Martin SG, Microtubule-dependent cell morphogenesis in the fission yeast. 2009. Trends in Cell Biology 19: 447-54.
Martin SG and Berthelot-Grosjean M. Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle. 2009. Nature 459: 852-6, Epub 2009 May 27.
Martin SG and Chang F. Dynamics of the formin for3p in actin cable assembly. 2006. Current Biology 16: 1161-1170.
Martin SG, McDonald WH, Yates JR 3rd, Chang F. Tea4p links microtubule plus ends with the formin for3p in the establishment of cell polarity. 2005. Developmental Cell 8: 479-491.
