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    <td><h2>BSCB Newsletter, Winter 2005</h2>
      <h2>FEBS/ESF Workshop on Integrated Approaches in Cytoskeleton 
        Research<br />
        Luxembourg, August 2005</h2>
      <p>I was fortunate to be awarded a BSCB Honor Fell travel 
        award to attend the FEBS/ESF Advanced Workshop on Integrated Approaches 
        in Cytoskeleton Research. My colleague, Clare Batchelor also attended, 
        with funding from FEBS, and has helped write this report. The meeting&nbsp; 
        was held in the beautifully renovated Neumunster Abbey in the Grund 
        area of Luxembourg City.</p>
      <p>By Jennifer Higginson and Clare Batchelor </p>
      <p>The opening lecture on the Saturday evening was given 
        by Eric Karsenti (EMBL, Heidelberg, Germany) on the self-organisation 
        principles of mitotic spindle assembly. He discussed the role of 
        molecular motors and chromosomes in organising the microtubules 
        during mitosis and explained that the robustness of spindle assembly 
        was due to the fact that these and other components would interact 
        in a certain way that would always generate a dynamic regime which 
        corresponds to what we call a mitotic spindle. </p>
      <p>The first session on Sunday addressed the Structure 
        and Assembly of Cytoskeletal Complexes.&nbsp; Yanagida Toshio (University 
        of Osaka, Japan) began by describing the investigation of actin 
        dynamics using single molecule FRET. His laboratory has found that 
        actin exists in two major spontaneously switching conformational 
        states, which are dependent upon myosin binding . This tells us 
        that filamentous actin is not a rigid structure, but plays a positive 
        role in cell motility.&nbsp; Ueli Aebi (University of Basel, Switzerland) 
        changed direction slightly by focusing on intermediate filaments 
        (IF). His group is approaching the tricky task of determining structural 
        information about IF proteins using a 'divide and conquer' approach, 
        which involves solving the structure of small protein fragments 
        individually, then gathering this information together to describe 
        IF structure, assembly and dynamics at the atomic level. </p>
      <p>Other speakers included Heidi Rommelaere (Gent University, 
        Belgium) who gave an interesting talk on the analysis of mutations 
        in the a-skeletal muscle actin gene, which give rise to congenital 
        myopathies, and&nbsp; Bernhard Wehrle-Haller (Centre Mdical Universitaire, 
        Geneva, Switzerland) who described his work on the differential 
        behaviour of integrin-dependent focal adhesion complexes in living 
        cells and the mechanism by which they are formed.</p>
      <p>The second session on 'Molecular Motors' began with 
        a very entertaining talk from Manfred Schliwa (University of Munich, 
        Germany), who described the mechanism of action of kinesin-1. Movement 
        of the kinesin protein along microtubules is initiated by ATP hydrolysis, 
        which then induces larger structural changes in the molecule.&nbsp; 
        By generating mutations in kinesin-1, his lab has found that these 
        changes are dependent upon key residues in the neck and hinge domain.&nbsp; </p>
      <p>We then heard an interesting talk by Mark Mooseker 
        (Yale University, USA) who discussed the phenotype of the Myo1a 
        knockout mouse.&nbsp; He has shown that Myo1a is essential for normal 
        development of the intestinal brush border in vertebrates. Kristopher 
        Clark (Nijmegen Centre for Molecular Life Sciences, The Netherlands) 
        presented evidence that TRPM7, a cation channel fused to an a-kinase, 
        can interact directly with actin and myosin II and its activation 
        regulates cell adhesion in mammalian cells through kinase-dependent 
        and -independent pathways. Finally, Sbastien Schaub (Swiss Federal 
        Institute of Technology, Switzerland) gave a fascinating presentation 
        on the mechanism of cell migration using a variety of microscopy 
        techniques in conjunction with computer tracking to study quantitively 
        the movement of actin and myosin II in highly motile fish keratocytes. </p>
      <p>Sunday afternoon was dedicated to Cytoskeletal Dynamics.&nbsp; 
        Alexander Bershadsky (The Weizmann Institute, Israel) focused on 
        the diaphanous-related formins and described a new function for 
        mDia in binding to the microtubule plus ends, believed to be a mechanism 
        of linking actin filaments to the growing microtubule ends. Alphe 
        Michelot (Grenoble, France) talked about formin 1 in Arabidopsis. 
        This formin appears to be able to function both as a 'leaky capper' 
        and as an Arp2/3 complex-like actin nucleator.&nbsp; Tijs Ketelaar 
        (Wageningen University, The Netherlands) gave us a stimulating insight 
        into plant root hairs and how these may be used to study cytoskeletal 
        dynamics in vivo. This was followed by an interesting explanation 
        by Cline Revenu (Institute Curie, Paris, France) of the many roles 
        of villin, from severing, to capping, bundling and nucleation of 
        actin filaments. Gemma Bellett (University of East Anglia) then 
        changed the theme somewhat, to talk about non-centrosomal micro-tuble 
        arrays.&nbsp; Her recent results advance the model of how apicobasal 
        microtuble arrays are generated in differentiated, polarised epithelial 
        cells. </p>
      <p>Monday began with a special session on Live Cell Imaging 
        and Emerging Technologies, which showed us new techniques for investigation 
        of the cytoskeleton.&nbsp; The first talk from Klemens Rottner (German 
        Research Centre for Biotechnology, Germany) addressed the conundrum 
        of WASP vs. WAVE in the activation of the ARP2/3 complex, using 
        techniques such as TIRF and epi-fluorescent timelapse microscopy. 
        The specificity of ARP2/3 is brought about by differential subcellular 
        positioning, possibly mediated by assembly into different protein 
        complexes.&nbsp; Rainer Pepperkok (EMBL, Germany) explained how 
        his group are using live cell imaging techniques together with mathematical 
        modelling to investigate the mechanisms regulating the early secretory 
        pathway through an interaction between specific vesicular coat complexes 
        and microtubule motor complexes. Finally, Julien Colombelli (EMBL, 
        Germany) gave a captivating presentation on the use of pulsed UV 
        laser nanosurgery to quantify cytoskeletal dynamics in vivo. </p>
      <p>After lunch, the session Nuclear Function of Cytoskeletal 
        Proteins was opened by Richard Treisman (Cancer Research UK, London) 
        who presented recent findings on how the cytoskeleton can influence 
        the regulation of gene transcription.&nbsp; The transcription factor, 
        SRF, is regulated by co-factors which shuttle continuously between 
        the nucleus and the cytoplasm.&nbsp; Nuclear import is controlled 
        by levels of G-actin and Rho GTPase signalling.&nbsp; Roland Foisner 
        (Medical University of Vienna, Austria) described the emerging function 
        of LAP2a, a lamina-associated polypeptide, in laminopathic diseases. 
        Lap2a is involved in chromatin organisation during mitosis and is 
        thought to control differentiation of adult stem cells when in a 
        complex with lamins A/C, through an interaction with Rb.</p>
      <p>Monday closed with a look at how model organisms can 
        be used to study the cytoskeleton. Angelika Noegel (University of 
        Cologne, Germany) described studies of CAP protein using Dictyostelium, 
        demonstrating a role for CAP in endocytosis and vesicle transport.&nbsp; 
        Jrgen Wehland (Braunschweig, Germany) then introduced us to bacterial 
        pathogens and talked about how we could learn a great deal about 
        actin dynamics by studying the actin-based motility of Listeria, 
        Shigella and pathogenic Escherichia coli. Raissa Elluere (IBSM-CNRS, 
        France) switched attention to yeast, in particular recent work on 
        the role of Bud3 in the regulation of the septin network of dividing 
        Saccharomyces cerevisiae. Finally, Sawako Yamashiro (Emory University, 
        USA) introduced UNC-60B and UNC-87, homologues of ADF/Cofilin and 
        calponin-like proteins, respectively, in Caenorhabditis elegans. 
        Essentially, she showed that UNC-87 inhibited the F-actin severing 
        activity of UNC-60B.</p>
      <p>Mary Beckerle (University of Utah, USA) opened Tuesday's 
        session on Integrated Cytoskeletal Circuits with her lab's recent 
        findings on Zyxin.&nbsp; They have shown that during uniaxial cyclic 
        stress, zyxin relocalises from the focal adhesions to the stress 
        fibres, where it seems to recruit Ena/Vasp and so induce thickening 
        of the stress fibres by actin polymerisation. Guy Tanentzapf (Gurdon 
        Institute, Cambridge) then described the role of talin in Drosophila 
        muscle. Talin appears to be essential for 'activation' of the integrin 
        at muscle attachment sites but is also necessary for recruitment 
        of other proteins to these sites. This suggests that talin has multiple 
        functional interactions within muscle attachment sites. Monique 
        Arpin (Institute Curie, Paris, France) gave an interesting description 
        of the multiple roles of the ERM protein family in plasma membrane 
        organisation and cellular signalling and Chen Luxenburg (Weizmann 
        Institute, Israel) presented recent data on the role of cortactin 
        and the Src tyrosine kinase in podosome formation. </p>
      <p>Wednesday started with a session entitled Biophysics 
        of the Cytoskeleton. Ccile Sykes (Institute Curie, Paris, France) 
        began by describing a method for mimicking Listeria function using 
        latex beads. Using this technique, they were able to measure the 
        physical forces required to move the 'bacteria'. In addition, to 
        try to understand the effects of actin polymerisation on the actin/myosin 
        cortex, they used solid beads or oil droplets coated with an actin/myosin 
        shell and demonstrated that the rigid bead caused cortex breakage, 
        whereas the more flexible oil droplet allowed deformation of the 
        cortex and propulsion of the bead by actin polymerisation. Marileen 
        Dogterom (AMOLF, The Netherlands) then described recent data on 
        force-generating </p>
      <p>microtubule dynamics. Her in vitro assay also utilised 
        beads, this time attached to a stiff microtubule-nucleating object. 
        Movement of the bead, generated by the growth of the microtubule, 
        could be measured in the presence and absence of various mictroubule-associated 
        proteins to determine their effects on microtubule dynamics. </p>
      <p>The final session on Cytoskeleton and Disease was 
        opened by Frans Ramaekers (University of Maastricht, The Netherlands) 
        who gave a very interesting description of using a cell compression 
        device to understand the underlying mechanisms of laminopathies. 
        Fibroblasts null for the lamin A/C gene have reduced mechanical 
        stiffness and weaker nuclei than wild-type ones. Mutations in lamins 
        result in total cellular weakness caused by a disrupted cytoskeleton.&nbsp; 
        The next speaker, John S. Condeelis (Albert Einstein College of 
        Medicine, USA), gave a fascinating presentation on the study of 
        metastasis by generating an 'invasion signature' for invasive cancer 
        cells using high-density micro-array analysis to identify key genes 
        that are up- or down-regulated in highly chemotactic cells.</p>
      <p>The local organisers, Evelyne Friederich and Andr 
        Steinmetz, did a wonderful job, choosing a well rounded scientific 
        programme in a lovely venue and arranging an excellent wine-tasting 
        excursion to the Moselle Valley. There were many interesting talks; 
        however, we could not mention them all, instead we have chosen a 
        good selection which we enjoyed. In addition, there were high quality 
        posters which led to some very interesting discussions.</p>
      <p>Jennifer Higginson and Clare Batchelor <br />
        Department of Biomedical Science<br />
        University of Sheffield<br />
        <a href="mailto:MD4JRH@sheffield.ac.uk">MD4JRH@sheffield.ac.uk</a></p></td>
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