Chairs
Professor Oscar Ces, Imperial College London, UK
Professor Oscar Ces, Imperial College London, UK
Professor Oscar Ces, a Professor in Chemistry at Imperial College London is a specialist in soft condensed matter, chemical biology, microfluidics, artificial cells, single cell analysis and lipid membrane mechanics. He has active research programmes with industry including collaborations with AstraZeneca plc, GSK plc, P&G plc and Syngenta plc. His current roles include: Co-Director of the Imperial College Advanced Hackspace, Co-Director of FABRICELL, Director of Development and Advancement (Chemistry), Director of the Institute of Chemical Biology (ICB), Director of the EPSRC ICB Centre for Doctoral Training and Co-Director of the Membrane Biophysics Platform. He is also a member of the steering committees for Agri-Net and the IC Nutrition and Food Network.
09:00-09:25
Regenerating the nuclear envelope during exit from mitosis
Dr Jeremy Carlton, KCL and Francis Crick Institute, UK
Abstract
During cell division, as well as separating their duplicated genomes, cells must also deconstruct, separate and then reconstruct many of their cytoplasmic organelles. Mammalian nuclei are surrounded by a double-membraned organelle called the nuclear envelope that is continuous with the endoplasmic reticulum. During mitotic exit, sheets of ER envelope the forming daughter nuclei and become fused together to generate a sealed nuclear envelope. In addition to its role in membrane abscission during cytokinesis, viral budding, endosomal sorting and plasma membrane repair, the endosomal sorting complex required for transport-III (ESCRT-III) machinery has recently been shown to participate in nuclear envelope sealing during mitotic exit. Nuclear envelope localisation of ESCRT-III is dependent upon the ESCRT-III component CHMP7 and the inner nuclear membrane protein LEM2. However, it is unclear how ESCRT-III actually engages nuclear membranes. Here, Dr Carlton shows that the N-terminus of CHMP7 acts as a novel membrane-binding module. This membrane-binding ability allows CHMP7 to bind to the endoplasmic reticulum (ER), an organelle continuous with the NE, and provides a platform to direct NE-recruitment of ESCRT-III during mitotic exit. Dr Carlton also identifies novel activities in the C-terminus of CHMP7 that restrict its activity to the inner-nuclear membrane and help us understand how this complex can help regenerate the nucleus. Dr Carlton finds that mutations that compromise CHMP7 function also prevent assembly of downstream ESCRT-III components at the reforming NE and proper establishment of post-mitotic nucleo-cytoplasmic compartmentalisation. These data identify a novel membrane-binding activity within an ESCRT-III subunit that is essential for post-mitotic nuclear regeneration.
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Dr Jeremy Carlton, KCL and Francis Crick Institute, UK
Dr Jeremy Carlton, KCL and Francis Crick Institute, UK
Jeremy obtained a BA in Natural Sciences from Cambridge University and then a PhD from the University of Bristol, where he examined membrane trafficking pathways regulated by the phosphoinositide-binding family of Sorting Nexins in Pete Cullen’s lab. After his PhD, he moved to the laboratory of Professor Juan Martin-Serrano in the Infectious Diseases department of King’s College London to examine how HIV-1 hijacks the ESCRT-machinery to allow its release from cells. Here, Jeremy described a novel and unexpected role for the ESCRT-machinery in cytokinesis and characterised the involvement of ESCRT-III proteins in an Aurora-B regulated abscission checkpoint. After his postdoc, Jeremy moved to the Division of Cancer Studies at King’s College London as a Wellcome Trust Research Career Development Fellow and then a Wellcome Senior Fellow. In Jeremy’s lab, the group continue their focus on membrane trafficking machineries and have described a novel role for the ESCRT-machinery in rebuilding the nuclear envelope during cell division.
09:35-10:00
Synthetic biology of minimal cellular systems
Professor Petra Schwille, Max Planck Institute of Biochemistry, Germany
Abstract
In recent years, biophysics has accumulated an impressive selection of cutting-edge techniques to analyse biological systems with ultimate sensitivity and precision, down to the single molecule level. However, a strictly quantitative application of most of these techniques in living cells or organisms has been extremely challenging, because of the enormous complexity and redundancy of cellular modules and elements. The more physiological a system under study, the harder it is to define a manageable number of relevant control parameters. This renders it necessary to accumulate ever more sophisticated techniques and assays in order to master a single biological problem, and thus, often extends experiments and publications in the life sciences to hardly manageable sizes. An alternative approach is to limit the methodological toolbox in a biological study without sacrificing the biophysical standards of quantitation. Instead, the biological phenomenon will have to be reduced to its fundamental features by reconstituting it in a bottom-up approach. The strive for identifying such minimal biological systems, particularly of subcellular structures or modules, has in the past years been very successful, and crucial in vitro experiments with reduced complexity can nowadays be performed, e.g., on reconstituted cytoskeleton and membrane systems. As a particularly exciting example for the power of minimal systems, we recently demonstrated the self-organization of MinCDE, essential proteins of the bacterial cell division machinery, leading to a protein-based pacemaker and spatiotemporal cue for downstream events, such as the positioning of divisome proteins. In her talk, Petra Schwille will discuss some recent results of her group’s work on membrane-based systems, using single molecule optics and biological reconstitution assays. Petra will further discuss the perspective of assembling a minimal system to reconstitute cell division.
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Professor Petra Schwille, Max Planck Institute of Biochemistry, Germany
Professor Petra Schwille, Max Planck Institute of Biochemistry, Germany
Petra Schwille is Director at the Max Planck Institute of Biochemistry in Martinsried near Munich, Germany, and Honorary Professor at the LMU Munich. She studied physics and philosophy in Stuttgart and Göttingen, and graduated 1993 with Diploma in Physics at the Georg August University, Göttingen. She obtained her PhD in 1996 performed at the MPI for Biophysical Chemistry, Göttingen. After a postdoctoral stay at Cornell University, Ithaca, NY, she returned to the MPI Göttingen as a research group leader. In 2002, she accepted a Chair of Biophysics at the TU Dresden. Since 2011, she is heading the department Cellular and Molecular Biophysics at the MPI of Biochemistry. Her scientific interests range from single molecule biophysics to the synthetic biology of reconstituted systems.
10:40-11:05
Buckling of an epithelium growing under spherical confinement
Dr Aurelien Roux, University of Geneva, Switzerland
Abstract
Many organs, such as the gut or the spine are formed through folding of an epithelium. While genetic regulations of cell fates leading to epithelium folding have been investigated, mechanisms by which forces sufficient to deform the epithelium are generated are less studied. Here, Aurelien Roux shows that cells forming an epithelium on to the inner surface of spherical elastic shells protrude inward while growing. By measuring the pressure and local forces applied onto the elastic shell, Aurelien shows that this folding is induced by compressive stresses arising within the epithelial layer: while growing under spherical confinement, epithelial cells are subjected to lateral compression, which induces epithelium buckling. While several fold initiations can be observed within one capsule, final shapes often show a single fold. These findings are recapitulated by an analytical model of the epithelium buckling from which the Roux group can estimate local compressive forces and rigidity. As proposed for gastrulation or neurulation, this study shows that forces arising from epithelium proliferation are sufficient to drive epithelium folding.
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Dr Aurelien Roux, University of Geneva, Switzerland
Dr Aurelien Roux, University of Geneva, Switzerland
As a PhD student (Curie Institute, Paris, 2000-2004) he worked between cell biologists (Bruno Goud’s lab) and physicists (Patricia Bassereau’s lab) studying how membrane properties influence various stages of membrane traffic. He found that Lo lipids, characterized by an increased bending rigidity of the liquid-ordered (Lo) phase they form compared to liquid-disordered (Ld) phase, were partially excluded from membrane tubules pulled from giant liposomes by molecular motors. This is due to the increased energy requirement for incorporating such lipids into curved structures (Roux et al., EMBO J, 2005). Even though postulated in the 80s, this study is the first experimental proof of curvature-dependent lipid sorting.
He went on with a post-doctoral work in Pietro de Camilli’s laboratory (2004-2007, Yale, USA). He created an assay with which he could monitor membrane fission induced by Dynamin (Roux et al., Nature 2006). After addition of GTP, he observed the contraction of the tubules and the formation of super-coils. This suggested a twisting activity of dynamin that he confirmed by attaching a small bead that rotated around the dynamin tubules during GTP hydrolysis. This study was the first study to show full reconstitution of membrane fission in an in vitro assay.
More recently, as CNRS staff scientist (2007-2010) and assistant professor of Biochemistry, Geneva (2010-present), he showed, together with his first PhD student Sandrine Morlot, that dynamin mediated-membrane fission occurs at the edge of its helix, explaining why constriction is required but not sufficient for fission (Morlot et al. Cell 2012).
In 2015, he has been promoted to associate professor the University of Geneva, and has in the meanwhile focused on two other protein assemblies, the ESCRT-III complex and the clathrin coat. He showed that clathrin assembly can be counteracted by membrane tension and rigidity (Saleem et al., Nat Commun. 2015), and that ESCRT-III proteins assemble into a spiraling filament which behaves like a spiral spring to deform the membrane (Chiaruttini et al., Cell 2015). Roux is a recipient of several prizes, including the 2013 Friedrich Miescher prize from the Swiss Biochemistry Society, and of an ERC grant.
11:15-11:40
Signalling reactions on membrane surfaces: the roles of space, force, and time
Professor Jay Groves, University of California, Berkeley, USA
Abstract
Most intracellular signal transduction reactions take place on the membrane. The membrane provides much more than just a surface environment on which signalling molecules are concentrated. There is a growing realization that multiple physical and chemical mechanisms allow the membrane to actively participate in the signalling reactions. Using a combination of single molecule imaging and spectroscopic techniques, Professor Jay Groves’ research seeks to directly resolve the actual mechanics of signalling reactions on membrane surfaces both in reconstituted systems and in living cells. These observations are revealing new insights into cellular signalling processes as well as some unexpected functional behaviours of proteins on the membrane surface. The Groves’ lab has recently discovered a type of signalling reaction phenomenon that enables geometrical features of the membrane surface to couple directly to the outcome of a signalling process.
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Professor Jay Groves, University of California, Berkeley, USA
Professor Jay Groves, University of California, Berkeley, USA
Jay Groves obtained a BS in Physics and Chemistry from Tufts University and a PhD in Biophysics from Stanford University. He has been a Professor in the department of Chemistry at the University of California, Berkeley since 2010. Jay has a broad background in physical chemistry and materials science as well as a long history of applying these skills to solve important problems in cell membrane biology and signal transduction. He invented the patterned supported membrane technology as well as its integration with living cells to create spatial mutations, in which the geometrical arrangement of molecules inside otherwise chemically identical living cells is altered in a controlled ways. Additionally, his research program has emphasized the advancement of optical tools including fluorescence spectroscopy, microscopy, and single molecule imaging to quantitatively analyze biological signaling processes on both reconstituted and living cell membranes. Jay’s research group is correspondingly diverse with students and postdocs from Physics, Chemistry, Biology and Engineering all working as a team. He has served as PI or co-PI on extramurally funded programs from NIH, NSF, DOE, DOD and NRF (Singapore) as well as a number of private foundations.
11:50-12:15
Harnessing Nature's ability to create membrane compartmentalisation
Dr Paul Beales, University of Leeds, UK
Dr Barbara Ciani, University of Sheffield, UK
Abstract
A biological cell can be thought of as a complex chemical reactor where vast numbers of interactions are simultaneously taking place. To prevent unwanted cross-talk and interference within the ‘noise’ of all these concurrent chemical pathways, a cell compartmentalises these processes localizing different functions within individual membrane-bound structures (organelles). Confinement of chemical processes also allows a cell to maintain incompatible environments that are optimal for each organelle's function, which would not be possible within a single ‘pot’. If we are to mimic this complexity within synthetic ‘nanoreactors’, we need to develop ways of mimicking cellular compartmentalisation within synthetic structures. Here, Dr Barbara Ciani and Dr Paul Beales will show that it is possible to create multi-compartment architectures, in vitro, using a purified membrane remodelling protein complex. Barbara and Paul will also show how this in vitro system allows us to learn what controls the membrane shaping action of these proteins and therefore regulate the encapsulation of cargo.
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Dr Paul Beales, University of Leeds, UK
Dr Barbara Ciani, University of Sheffield, UK
Dr Paul Beales, University of Leeds, UK
Paul is an Associate Professor in physical chemistry at the University of Leeds. With a background in soft matter and biological physics, his current research interests are encompassed by the physical properties and applications of biomimetic membranes. Specific recent and current research topics that contribute to the synthetic biology toolbox for development of artificial cells include membrane texturing through phase separation, artificial DNA adhesion receptors, hybrid lipid-polymer membrane systems for enhanced stability and lifetime, encapsulation of feedback-responsive systems and controlled generation of eukaryote-like membrane architectures.
Dr Barbara Ciani, University of Sheffield, UK
Dr Ciani obtained a Laurea in Chemistry at University "La Sapienza" in Rome (1997). This was followed by a DPhil in Biochemistry at the School of Biological Sciences of the University of Sussex (2002). She was a postdoctoral research associate at the Department of Chemistry of the University of Nottingham (2001-2003), and at the Wellcome Trust centre for Cell Matrix research of the University of Manchester (2004-2008). In 2008, she was appointed as a Lecturer in Biophysical Chemistry at the Department of Chemistry of the University of Sheffield.