Sheffield Biological Physics Seminar Series

2016

Date	Speaker & Title	Place
2pm 30th Nov	Jonny Burns, Jamie Hobbs' Group, University of Sheffield High Resolution AFM of Living S. aureus Bacterial Cell Wall Abstract The aim of the project is to use the high resolution Atomic Force Microscopy (AFM) techniques to image living bacterial surfaces, over the course of the bacterial life cycle, to measure changes in the morphology and the architecture of the peptidoglycan chains that make up the bacterial cell wall. The study of bacteria is important for understanding disease, the development of drugs, understanding bacterial ecosystems like in the human gut and in biotechnology research. AFM has become a widely used technique in biological studies due to its versatility and high resolution imaging capability. Staphylococcus aureusis a model Gram positive bacterium with a peptidoglycan cell wall. The bacterial cell wall gives the bacteria their shape and allow them to maintain their osmotic pressure. The architecture of the peptidoglycan changes as the material ages. Previous studies of S. aureus have allowed for models of the structure and physical properties of the bacterial cell wall peptidoglycan to be built using living and dead cells. The spherical bacterial cells can be immobilised using silicon wafers with etched holes that allow for the cells to be imaged repeatedly. High resolution imaging of live cells is achieved by tapping with a small cantilever AFM and through optimisation of imaging buffer. High resolution images of S. aureus cells have been taken at different time points revealing the detailed architecture of the cell wall with molecular resolution on living bacteria. Different structures are observed for different regions of the cell wall, depending on the age, with a transformation from tightly spaced concentric rings to a loose mesh. The ability to directly visualise the molecular architecture of a living pathogen promises to open up new avenues for understanding the action of common antibiotics such as penicillin.	LT D
6pm Tues 6th Dec	lecture Tomas Lindahl FRS FMedSci, Francis Crick Institute, 2015 Nobel Prize Winner
2pm 16th Nov	Shiladitya Banerjee, University College London "Design principles and mechanics of contractile actin networks, bundles and drops" Abstract Mechanical stresses generated by the actomyosin cytoskeleton can drive large-scale structural changes and shape transformations at cellular or tissue scales. The shape and the contractile or extensile nature of cytoskeletal deformations are specific to different physiological tasks and may be important for their proper execution. Using a minimal biomimetic model of actomyosin cytoskeleton, we demonstrate that cooperative contractility can robustly emerge in actomyosin networks independent of the network architecture and is scalable with the total active myosin content. Using in vitro experiments and agent-based simulations we show that the contraction modes of actin networks can be robustly tuned by modifying the filament rigidity and cross-linking density. Our study further demonstrates a novel liquid phase of filamentous actin in the presence of flexible crosslinking proteins, which can be used to modulate the amount of surface tension and viscosity in the material. These crosslinked actin bundles near a liquid-solid transition display the characteristic dynamics and instabilities of nematic fluids and are capable of spontaneous contraction without molecular motors.	LT D
2pm 23rd Nov	John Mackenzie, University of Strathclyde "Local modulation of chemoattractant concentrations by single cells: dissection using a bulk-surface computational model" Abstract Chemoattractant gradients are usually considered in terms of sources and sinks that are independent of the chemotactic cell. However, recent interest has focused on “self-generated” gradients, in which cell populations create their own local gradients as they move. Here we consider the interplay between chemoattractants and single cells. To achieve this we extend a recently developed computational model to incorporate breakdown of extracellular attractants by membrane-bound enzymes. Model equations are parameterised using published estimates from Dictyostelium cells chemotaxing towards cyclic AMP. We find that individual cells can substantially modulate their local attractant field under physiologically appropriate conditions of attractant and enzymes. This means the attractant concentration perceived by receptors can be a small fraction of the ambient concentration. This allows efficient chemotaxis in chemoattractant concentrations that would be saturating without local breakdown. Similar interactions in which cells locally mould a stimulus could function in many types of directed cell motility, including haptotaxis, durotaxis and even electrotaxis.	LT D
2pm 9th Nov	Tania Mendonca, Ashley Cadby's Group, University of Sheffield 3D Visualisation of Oviductal Sperm Selection with Light Sheet Microscopy Abstract Light sheet microscopy has made it possible to investigate biological processes live, and in the context of their natural spatio-temporal environment. Here we describe a novel application of light sheet microscopy to investigate one such set of processes - sperm selection - in the avian oviduct. The oviduct is a complex 3D space comprised of thick scattering tissue and presents several challenges for live imaging. Light sheet microscopy allows for fast optical sectioning, deep into the oviduct tissue while inflicting low levels of photo-toxicity and photo-bleaching, making it ideal for imaging dynamic interactions between this complex space and the fast moving sperm.	LT D
2pm 26th Oct	Sam Barnett, Ashley Cadby's Group, University of Sheffield "Perfect exposure for single molecules" Abstract Super-resolution microscopy has improved the ability to image details below the diffraction limit. However the resolution increase (specifically with localisation microscopy) is highly dependent on the signal to noise ratio of the measurement. We have used Non-Destructive Readout technology to match the exposure to individual transiently fluorescing single molecules; thus increasing the signal to noise ratio and the resulting image quality.	LT D
2pm 19th Oct	seminar Rosalind Allen, University of Edinburgh "How does bacterial growth environment affect antibiotic efficacy and the evolution of resistance? " Abstract Many experiments on bacterial action and the evolution of resistance are done in standardised lab conditions, yet bacteria in infections experience complex growth conditions, which can vary in time and space. Exposure to nutrients can also vary between different infections. We have investigated how the richness of the nutrient medium affects the efficacy of action of ribosome-targeting antibiotics. We find apparently conflicting results: some ribosome targeting antibiotics work better on rich media while others work better on poor media. These results can be explained by a simple mathematical model. I will also describe theoretical and preliminary experimental work on the effect of spatial gradients of antibiotic on the evolution of resistance.	LT 6
2pm 12th Oct	Nic Mullin, University of Sheffield "Imaging molecules in context - high resolution AFM imaging on biological systems" Abstract Atomic Force Microscopy (AFM) is a tool that allows imaging of biological samples with sub-nanometre resolution under near physiological conditions without labelling or staining. In the work presented here, the physics of dynamic AFM will be reviewed in the context of optimising the AFM for high resolution on soft samples. High resolution data will be presented for several biological samples currently being investigated in Sheffield, including an ongoing correlative AFM and transmission electron microscopy study of the molecular architecture of the bacterial exosporium.	F24
2pm 5th Oct	Tim Craggs, University of Sheffield, Dept of Chemistry "Single-molecule FRET for structural biology" Abstract Single-molecule Förster Resonance Energy Transfer (smFRET) is now an established method for studying biomolecular conformation and dynamics. I will give an overview of the utility of this method, with examples from our work on DNA Polymerase I. I will then present our most recent work establishing smFRET as a tool for structural biology. We show that smFRET can be used to determine accurate, absolute distances, with a bench mark study from 20 labs around the world, all consistently measuring the same (blind) samples with a standard deviation of 0.3 nm. Finally I will show how we have used this method to determine a novel structure of DNA Polymerase I bound to its gapped DNA substrate. The complex shows that the DNA substrate is significantly bent, with 4-5 nucleotides of the downstream duplex proximal to the gap unwound. Further, experiments and coarse-grained modelling showed the substrate alone frequently adopts bent conformations with 1-2 nt frayed around the gap, suggesting a mechanism in which Pol recognises a pre-bent, partially-melted conformation of the gapped-DNA.	LT D
2pm Tues 24th May	Dr Simon Martin, Loughborough University "Interfaces between materials and between disciplines (Or: why crap research is not always a bad thing)" Abstract Working as a physicist in a Materials Engineering Department throws up some interesting research opportunities. In this presentation I will discuss two of what I consider to be the most interesting projects that I have worked on recently. Key themes running through both topics are the importance of interfaces and the importance of working with interdisciplinary teams. First I will discuss the work I was involved with on the "Re-invent the Toilet Challenge" sponsored by the Bill and Melinda Gates Foundation which involved designing and developing a toilet system that could operate off-grid for no more than $0.04 per user per day. An initially mad sounding challenge turned into a heady mixture of thermodynamical balances, self-assembled polymer brush layers, design ergonomics, and more. Second, I will describe the Next Generation Prosthetics project at Loughborough University. This is a highly speculative project that aims to create the technology required to enable the additive manufacture of prosthetic limbs that provide natural movement and connect directly to the wearer's nervous system.	LT D
2pm 8th June	Dr Annette Taylor, University of Sheffield, Chemical and Biological Engineering "Exploitation of Dynamic Instabilities in Active Matter" Abstract Active matter that is maintained far from equilibrium by use of a chemical fuel can display dynamic instabilities arising from a combination of reaction and transport of chemical species. In this talk I will cover three different types of instability in synthetic systems: (a) motion and interaction of crystals at the air-water interface as a result of surface flows [1] (b) chemical switches and pulses in bio-catalytic cells[2] (c) time-lapse gelation and propagating gel fronts.[3] How living organisms exploit these instabilities will be discussed and possible applications in materials will also be explored. 1. Bansagi T, Wrobel MM, Scott SK, Taylor AF. J Phys Chem B 2013. 2. Muzika F, Bansagi T, Schreiber I, Schreiberová L, Taylor AF. Chem. Comm. 2014, 50, 11107. 3. Jee E, Bansagi, T, Taylor AF and Pojman J Angew. Chem. Int. Ed. 2016, 55, 2127.	LT D
2pm 18th May	Dr Lorna Dougan, University of Leeds "Structural studies of hydrogen bonded liquids at low temperatures" Abstract Liquid water plays a fundamental role in life on Earth. Covering a wide temperature and pressure range, water's presence is crucial for a vast range of biological, geological and environmental processes. Despite this importance and ubiquity a full understanding of its dynamical and structural properties remains lacking. The unusual properties of water, which include anomalies in its thermodynamic quantities, are more enhanced at lower temperatures and may result from the local tetrahedral ordering due to hydrogen bonding. I will present recent work in which we have been exploring a binary liquid system which can be exploited to experimentally probe the structure of liquid water in equilibrium at temperatures down to 238 K. We make use of a cryoprotectant molecule, glycerol which when mixed with water lowers the freezing temperature of the solution non-monotonically with glycerol concentration. We use a combination of neutron diffraction and computational modeling to examine the structure of water in glycerol - water liquid mixtures at low temperatures from 285 K to 238 K. We confirm that the mixtures are nano-segregated into regions of glycerol-rich and water-rich clusters. We examine the water structure and reveal that at the sub-zero temperatures studied here, water forms a low density water structure which is more tetrahedral than that at room temperature. We hypothesize that nano-segregation allows water to form a low density structure which is protected by an extensive and encapsulating glycerol interface.	LT6
2pm 4th May	Dr Alex Fletcher, University of Sheffield, School of Mathematics and Statistics "Cell-based modelling of epithelial morphogenesis" Abstract The dynamic behaviour of epithelial tissues plays a central role during development. These processes occur as a result of cell adhesion, migration, division, differentiation and death, and involve multiple processes acting at the cellular and molecular level. In combination with experimental studies, mathematical modelling can help us understand what factors are involved in regulating cell- and tissue-level behaviour, and how this can go wrong. In this talk I describe our recent application of 'cell-based' modelling approaches to understand aspects of epithelial dynamics in several settings, including tissue size control and pattern repair in the Drosophila embryonic epidermis. I highlight the biological insights gained through this work, as well as ongoing challenges associated with such modelling approaches.	LT6
11am 6th April	Olof Johansson, University of Edinburgh "Femtosecond charge and spin dynamics in the V-Cr Prussian Blue Molecule-Based Magnet" Abstract Molecular magnets show large potential for the development of new quantum computers and spintronics devices since their properties can be controlled at the nanometre-scale due to their chemical flexibility. The possibility to switch the spin configuration of these materials to metastable states using external perturbations offers exciting opportunities for developing high-capacity information storage devices operating at high switching speeds. Since the surprising discovery in 1996 by Bigot et al. that short femtosecond laser pulses can demagnetise nickel, the field of "femtomagnetism" has grown rapidly and is attracting interest from industry due to the potential to read and record information 1000 times faster than what present computer memories can achieve. Subsequent developments in ultrafast magneto-optical (MO) techniques have made it possible to study magnetic processes on unprecedented timescales in various magnetic metals and dielectrics. However, molecular materials have so far been under-explored using ultrafast MO techniques. We have used femtosecond pump-probe spectroscopy to measure the MO and transient transmission dynamics in thin films of the VII/IIICrIII Prussian Blue Analogue (PBA), which is a room-temperature molecule-based magnet. We demonstrate that exciting the films at the ligand-to-metal charge-transfer band leads to a sub-ps change in the MO signal. This is attributed to a modification of the super-exchange interaction between the metal ions caused by a change in spin configuration after the optical excitation. We believe that these measurements open up new possibilities to expand the field of ultrafast magnetism to study spin dynamics in novel magnetic molecular materials.	LT B
3pm 2nd March	Dr Carl Whitfield, University of Sheffield now University of Warwick "Modelling Spontaneous Motion and Deformation in Active Droplets" Abstract Active matter is a family of materials that are driven out of thermal equilibrium by converting internal energy into work at the level of individual constituent particles. There are many examples of active matter systems at all length scales in biology, from the cell cytoskeleton to flocks of birds and mammals. In this talk I will consider specifically a continuum model of an active fluid , which is a simplified model of the cell cytoskeleton. We predict, analytically and numerically, a variety of spontaneous symmetry breaking behaviour driven by activity when this material is confined to, on or around droplets immersed in a passive fluid. These activity driven instabilities can lead to rich phase behaviour of the droplets including steady state motility, deformation, and oscillations. I will discuss how these states may be observed experimentally in vitro using reconstituted cytoskeletal networks and also the limitations of this model. Finally, I will demonstrate ways this model can be improved in the future to closer represent a model of cytoskeleton driven motility and deformation in animal cells.	LT E
2pm 24th Feb	Cristian Fernandez Oto, University Libre de Bruxelles, Brussels "Spiral Vegetation Patterns and Fairy Circles" Seminar joint with Maths (MathsBio) Abstract When plant communities suffer the stress of limited resources and adverse environmental conditions, the spatial homogeneity of the biomass is lost and self-organized patterns arise. Here, I will talk about two different structures. First, I will report the observation of Spiral Vegetation Patterns, under highland arid conditions in the north of Chile. The spiral arms are few meters long and some centimeters wide. We attribute their formation to an 'excitable' behavior of the barren state that we mathematically describe as a coupling between vegetation in semiarid regions and a typical herbivore in the region where spirals were observed. After, I will present our work in Fairy Circles. Fairy circles consist of circular areas devoid of any vegetation. They are observed in vast territories in southern Angola, Namibia and South Africa and their diameters are few meters. We interpret them as localized structures with a varying flat area as a function of the aridity. Their stabilization mechanism is attributed to a combined influence of the bistability between the bare state and the uniformly vegetation state, and Lorentzian-like nonlocal coupling that models the competition between plants. We show how a circular shape is formed, and how the aridity level influences the size of fairy circles.	LT E

2015

Date	Speaker & Title	Place
4pm 16th Dec	Dr Laurence Wilson, University of York "Holograms, diffraction and other tricks with computational imaging" Abstract Digital cameras and computers are abundantly available. For example, modern mobile phones are equipped with high-resolution CCD sensors and powerful, multi-core CPUs. Despite these advances, the optical elements in phone cameras are based on designs that are at least 100 years old. Modern innovations include refinements in lens shape and antireflection coatings, but the overarching principle is the same as it has been for over a century - to capture a sharply-focused image of a scene that mimics the way in which our eyes see things. Optical microscopes have also been extensively optimised over the last century. The introduction of contrast generation techniques like Zernike phase contrast and differential interference contrast (DIC) have enabled microbiologists and others to image their samples in greater levels of detail. Consequently, optical microscopes are increasingly complex (and expensive) because of their intricate optical and mechanical design. Instead of trying to further refine these mature technologies, we have been re-thinking the broader relationship between the camera and the computer. We use an understanding of physical optics at microscopic scales, coupled with statistical techniques, to extract extra information from a transmitted-light optical microscope. I will give a few examples of analysis routines that we've been working on that show this approach. I will describe some scattering-based methods, as well as high-speed, three-dimensional holographic microscopy. In both cases, I will show the new insight these physics-based methods give into microbiological experiments. Followed by Christmas drinks & nibbles in the Austin Room	LT D
3pm Fri 4th Dec	Dr Susan Cox, King's College London Centre for Doctoral Training in Molecular-Scale Engineering Christmas Lecture "Information in Super-resolution Microscopy" Abstract Fluorescence localisation microscopy allows cells to be imaged with a resolution down to 20nm. Both creating and understanding the significance of these images requires the extraction of information, either by using image analysis or by processing the resulting localised positions to enable a measurement of some characteristic of the sample. In this talk I will explore three different aspects of information in localisation microscopy: the limitations it places on the speed at which measurements can be carried out, how improved modelling of fluorophore photophysics can boost both speed and resolution, and a novel way to extract information about clustering in data.	Arts Tower LT 5
2pm 9th Dec	Prof Pete Vukusic, University of Exeter "Evolutionary light manipulation in biological systems" Abstract In many biological systems such as insects, fish, birds and flowers, the common mechanism for the most brightly coloured appearances is coherent scattering from photonic crystal structures. Study of these systems is informing a broad range of sciences, providing not only functional, behavioural and materials understanding, but also suggesting protocols with which light, colour and appearance manipulation in technology may be more effectively embraced. This presentation will offer an overview of the field of biological photonics, and will present in detail several recent discoveries that reflect nature's optical design ingenuity, combined with some technological applications for which they are currently being developed.	LT D
1pm 25th Nov	Dr Guillaume Charras, University College London (UCL) Joint seminar with MBB (Molecular Biology and Biotechnology) "Biophysical mechanisms of oriented tissue growth in epithelial monolayers" Abstract Cell division plays an important role in animal tissue morphogenesis, which depends, critically, on the orientation of divisions. In isolated adherent cells, the orientation of mitotic spindles is sensitive to interphase cell shape and the direction of extrinsic mechanical forces. In epithelia, the relative importance of these two factors is challenging to assess. To do this, we used suspended monolayers devoid of ECM, where divisions become oriented following a stretch, allowing the regulation and function of epithelial division orientation in stress relaxation to be characterized. Using this system, we found that divisions align better with the long, interphase cell axis than with the monolayer stress axis. Nevertheless, because the application of stretch induces a global realignment of interphase long axes along the direction of extension, this is sufficient to bias the orientation of divisions in the direction of stretch. Each division redistributes the mother cell mass along the axis of division. Thus, the global bias in division orientation enables cells to act collectively to redistribute mass along the axis of stretch, helping to return the monolayer to its resting state. Further, this behavior could be quantitatively reproduced using a model designed to assess the impact of autonomous changes in mitotic cell mechanics within a stretched monolayer. In summary, the propensity of cells to divide along their long axis preserves epithelial homeostasis by facilitating both stress relaxation and isotropic growth without the need for cells to read or transduce mechanical signals.	Firth Court F2
2pm 18th Nov	Dr Rosemary Harris, Queen Mary University of London "Fluctuations in stochastic systems with memory" Abstract I will give a gentle introduction to some recent work on the effects of long-range temporal correlations in stochastic particle systems, focusing particularly on fluctuations about the typical behaviour. Specifically, in the first part of the talk, I will discuss how long-range memory dependence can modify the large deviation principle describing the probability of rare currents and lead, for example, to superdiffusive behaviour. In the second part of the talk, I will describe a more interdisciplinary project incorporating the psychological "peak-end" heuristic for human memory into a simple discrete choice model from economics. Along the way, I will attempt to indicate connections between different approaches, other possible applications (especially to biology), and open questions.	LT E
2pm 11th Nov	Dr Ling Chin Hwang, MBB, University of Sheffield "Spatial organization in bacteria: using protein patterns to generate motion" Abstract Recent advancements in fluorescence microscopy have revealed that bacteria are more than just bags of enzymes, and instead have complex intracellular organization. It was observed that bacterial genomes segregate with distinct spatiotemporal patterns during cell division but how this generates DNA movement is unclear. We reconstituted in vitro a minimal DNA segregation system and visualized the system dynamics with single-molecule fluorescence microscopy. We found that bacteria use a protein patterning mechanism to drive the intracellular transport of DNA. We also investigated a similar self-organization system that is involved in positioning the cell division machinery of E.coli. Combining biochemistry and fluorescence microscopy techniques, we aim to understand how bacteria use molecular patterning for intracellular transport and organization.	LT E
2:30pm 4th Nov	Dr Ewa Paluch, MRC LMCB, UCL, London "Actin cortex and cell surface mechanics across scales, from molecular processes to cell-scale behaviours" Abstract The shape of animal cells is primarily determined by the cellular cortex, a thin network of actin filaments and myosin motors bound to the plasma membrane. We investigate how the mechanical properties of the cell surface arise from the microscopic organisation of the cortical network and of the plasma membrane, and how changes in these properties drive cell deformation. We have developed methods to investigate the nanoscale architecture of the cortex and are exploring how the organisation of actin filaments controls network mechanics. We also investigate how the spatial distribution of motor proteins in the cortex modulate cortical tension. By combining cell biology experiments, quantitative imaging and theory, we aim to understand cell surface tension generation across scales.	LT E
3pm 21st Oct	Dr Martin Greenall, University of Lincoln "Controlling aggregate size and domain formation in amphiphile self-assembly" Abstract The design of amphiphilic membranes for applications can be guided and focused by theory and computer simulations. Here, we use mean-field theory to investigate three related problems. Firstly, we demonstrate how adding oil molecules of a carefully chosen size to mixed bilayers can encourage domain formation by reducing the excess membrane surface area and curvature arising from the size mismatch of the two amphiphiles. Next, we provide a concrete theoretical demonstration of the basic principle that amphiphile architecture can directly control vesicle radius if the membrane symmetry is broken by the use of copolymers with multiple hydrophilic and hydrophobic sections. We present a comprehensive investigation of tetrablock (ABCA) copolymers and show how these could be designed to form strongly monodisperse vesicles of a specified size while suppressing the formation of other structures. Finally, we turn our attention to a problem that links the first two: the disk-like mixed membranes, known as bicelles, that form in mixtures of micelle-forming and lamella-forming amphiphiles in solution. We show that these disks have a preferred size, and go on to identify a copolymer/homopolymer system where they are predicted to be stable, forming a suspension of hard disks in a fluid homopolymer.	LT9
2pm 14th Oct	Prof Paul Meredith, Global Change Institute, University of Queensland, Australia "Organic Optoelectronics and Bioelectronics - New Frontiers in Advanced Materials" Abstract Inorganic semiconductors are arguably the fundamental technological building blocks of our modern world - we have been living in the "silicon age" since the 1960s. Organic semiconductors have emerged during the past decade as the potential next step in the evolution of low cost, low embedded energy semiconductors and have found applications in light emission, light harvesting, detection and sensing. Organic semiconductors are molecular solids and as such intrinsically disordered - this limits their transport physics and will likely mean that we will never see high speed electronics based upon these materials. However, they are efficient light emitters and can have photon-to-conversion efficiencies approaching 100% across multiple spectral windows. In my talk I will describe some of the pertinent electro-optical physics of organic semiconductors of relevance to applications such as solar cells and photodiodes [1, 2]. I will cover new applications in the emergent field of bioelectronics, which is natural extension of the reach of organic semiconductors, and particularly focus on our progress in developing ion-to-electron transducing elements [3]. Finally, I will bring these two areas of modern advanced materials together to explain some of the basic physics of the current "superstars" of materials science - the organohalide perovskites [4] and summarise our recent development of the first Red, Green, Blue filterless photodiodes [5]. [1] "Narrowband light detection via internal quantum efficiency manipulation of organic photodiodes", A. Armin, R. D. Jansen-van Vuuren, N. Kopidakis P. L. Burn & P. Meredith, Nature Communications, 6, 6343 (2015). [2] "Hot excitons or optical effects in organic solar cells", A. Armin, Y. Yang, P.L. Burn, P. Meredith & A. Pivrikas, Nature Materials, 12(7), 593 (2013). [3] "Electronic and optoelectronic materials and devices inspired by nature", P Meredith, C.J. Bettinger, M. Irimia-Vladu, A.B. Mostert & P.E. Schwenn, Reports on Progress in Physics, 76, 034501 (2013). [4] "Electro-optics or perovskite solar cells", Q. Lin, A. Armin, R.C.R. Nagiri, P.L. Burn & P. Meredith, Nature Photonics, 9, 106-112 (2015). [5] "Low noise, IR-blind organohalide perovskite photodiodes for visible light detection and imaging", Q. Lin, A. Armin, D.M. Lyons, P.L. Burn & P. Meredith, Advanced Materials, 27(12), 2060-2064 (2015). [4] "Filterless, narrowband RGB photodetectors", Q. Lin, A. Armin, P.L. Burn & P. Meredith, Nature Photonics, doi:10.1038/nphoton.2015.175 (2015).	LT D
2pm 7th Oct	Dr Jocelyn Etienne, Grenoble "How to look elastic when you're liquid: emergent material properties of the cell's polymeric skeleton" Abstract Living cells adapt and respond actively to the mechanical properties of their environment. In addition to biochemical mechanotransduction, evidence exists for a purely mechanical sensitivity to the stiffness of the surroundings at the cell-scale. Using a minimal model that describes the collective behaviour of actin, actin crosslinkers and myosin, we show that the mechanosensitive response of cells spreading between distant elastic microplates is entirely and quantitatively predicted by the behaviour of the actomyosin cortex as a contractile viscoelastic fluid. Because cells actively regulate their size by deforming their environment if it is sufficiently compliant, their apparent behaviour is the one of a spring: this is an emergent mechanical property of their viscoelastic cytoskeleton which uses biochemical energy to maintain its shape.	LT D
2pm 30th Sept	Dr Rosemary Staniforth, MBB, University of Sheffield "Slowing down Alzheimer's disease: intricate fibril conformations key to exploiting our natural defences"	LT D
2pm Wed 15th July	Prof Kristian Muller-Nedebock, Stellenbosch University, South Africa "Dynamical networks of filaments with applications to active systems: motor attachments, linking, and stepping on filaments" Abstract Reversibly cross-linked networks of polymers or filaments occur in a variety of systems. When the cross-linking itself consists of molecular motors or clusters of molecular motors, the description of a constantly remodelled network becomes necessarily dynamical. Not only do the so-called active gels formed by this linking, and possible other static cross-links, show interesting active behaviours produced by the motions of the motors, but contractile rings pose interesting dynamical questions. Underlying an adequate analytical formulation is the necessity to introduce suitable dynamical constraints that incorporate the respective roles of networking and motion properties of motor clusters. We apply such concepts to general networks, different stepping mechanisms for motor proteins and to cast some light on the origins of the tension and structural integrity of the contractile ring.	L.T.7
2pm Fri 3rd July	Yukari Oda, Kyushu University, Japan "Control of Interfacial Structure and Dynamics of Vinyl Polymers for Bio-applications" Abstract Excellent bio-inert properties of polymeric materials are strongly affected by the chain behavior such as structure and dynamics at the water interface, which should be controlled by the polymer design. However, the relationship between them has not been systematically investigated. In this study, a poly(vinyl ether) with oxyethylene side-chains (POEVEs) is focused because it lacks a carbonyl group in the side-chain part compared to the acrylate polymers. Rubbery POEVEs possess low surface free energy due to their activated molecular motion, leading to a preferential segregation at the air interface in a diblock copolymer with glassy poly(cyclohexyl vinyl ether) (C). The block copolymer films successfully suppressed platelet adhesion and its activation. Aggregation states of the polymer chains as well as water molecules at the interfaces were examined using sum-frequency generation vibrational spectroscopy. The surface structure of the polymer films was altered in contact with water, leading to a variation of the aggregation states of water molecules at the interface. Furthermore, the physical properties and dynamics of the polymer interfaces in water were also examined using scanning probe microscopy. The obtained knowledge should be crucial to the design and construction of highly functionalized polymer interfaces for bio-applications.	LT6
11am 24th June	Prof Annick Lesne, CNRS, LPTMC (Paris) and IGMM (Montpellier) "Physics of chromosomes and its role in the regulation of gene expression" Abstract An important feature of the eukaryotic genome is its multiscale organization, from the level of the DNA molecule to the chromatin fiber to the chromosomes. I will show that such a structural and spatial organization is associated with physical constraints, controlling the DNA binding landscape and shaping the space of possible conformations of the chromatin fiber. We have proposed an extended notion of allostery, chromatin allostery, in which conformational transitions of either the embedded DNA, or at a larger scale of the fiber itself, may control at a distance transcriptional events. This notion offers a framework to understand the interplay of physical mechanisms and specific biological factors involved in the epigenetic regulation of gene expression. Some references: Care et al. Commun. Theor. Phys. 62, 607 (2014) Lesne et al. Nature Methods 11, 1141 (2014) Lesne et al. J. Phys. Cond. Matter 27, 064115 (2015)	F28
2pm Monday 29th June	Fred Combley Colloquium Prof Marileen Dogterom, TU Delft, The Netherlands "A minimal synthetic biology system to create spatial protein patterns in yeast" Abstract Establishment of cell polarity is essential for processes such as growth and division. In fission yeast, polarity factors travel at the tips of microtubules to the cell ends where they associate with the membrane and subsequently maintain a polarized pattern. While many molecular components have been shown to play a role in this polarization process, it remains unknown which molecular functionalities are minimally required. We show that a single chimera protein that combines a membrane-binding motif with microtubule tip affinity is able to transiently concentrate at cell ends in wild type fission yeast cells. In addition, we established an in vitro system that allows us to verify the minimal molecular requirements for microtubule-based cell polarity. We used micro-fabrication techniques combined with surface functionalization to create rigid chambers with affinity for proteins, and microfluidic techniques to create elongated emulsion droplets with functionalized lipid boundaries. We demonstrate that proteins, which concentrate and cluster at the ends of growing microtubules, can be delivered to the boundaries of these confined spaces. Interestingly, protein clusters, but not individual proteins, remain at the boundaries for several minutes after the microtubules disappear.	LT01
2pm 27th May	Peter Petrov, University of Exeter "Membrane thermal fluctuations: red cells as morpho-elastic probes" Abstract A number of essential functions in mammalian cells, such as passive and active transport, signalling, recognition, motility etc., are known to reside in the plasma membrane and to be critically dependent on the membrane composition, structure and physical properties. The lipid bilayer, far from being merely a matrix for embedding the membrane proteins, has been shown to contribute to membrane function via its effects on protein conformation, stability, assembly and distribution. A deeper understanding of the composition-structure-function relationship in the plasma membrane requires quantification of membrane mechanics. Over the past several years, we have been investigating the mechanical properties of the red blood cell (RBC), in its own right, and as a generic model of the plasma membrane. We have developed novel experimental methods, using advanced optical microscopy in combination with particle dynamics simulations, of characterising these properties based on the analysis of membrane thermal fluctuations, which allowed us to quantify membrane mechanical properties in terms of well-defined physical quantities. In this talk, I will show how this approach can be used to determine the effects of oxidative stress on RBC membrane mechanics in vitro, and assess the effects of glycation (as a model for diabetes mellitus) on membrane susceptibility to oxidative stress. I shall argue that changes in the mechanical properties of the RBC are likely to provide a sensitive and revealing probe of the exposure to oxidative and other chemical stress in disease. I will also show how RBC can be used as a marker for antioxidative properties of drugs and present results on the effects of metformin, a common anti-diabetic drug, which demonstrate that it can reverse the damaging effects of glycation in red cells and ameliorate the response of glycated cells to oxidative stress.	LT D
2pm 13th May	Dr Richard Graham, University of Nottingham "Modelling polymer crystallisation under flow: from molecular shape to flow properties and crystallisation" Abstract Polymer molecules, due to their size, move much more slowly than simple molecules. They are sufficiently slow that flow can unravel individual chains. This molecular deformation leads to flow properties that are richly non-linear and strongly non-Newtonian. Furthermore, molecular deformation drastically increases the rate of crystallisation in polymers and changes the resulting crystal structures. By distorting the configuration of polymer chains, flow breaks down the kinetic barriers to crystallisation and directs the resulting crystallisation. These effects are of central importance to the polymer industry as crystallisation determines virtually all of the useful properties of polymer products. However, modelling polymer crystallisation is extremely challenging due to the huge spread in relevant lengthscales and timescales. Furthermore, the most pronounced crystallisation effects are seen at low undercooling. In this temperature regime the nucleation of small crystals, from which bulk crystallisation occurs, is extremely slow. This makes crystallisation especially difficult to simulate because the nucleation dynamics are controlled by extremely rare activated crossing of the nucleation barrier. We have recently been using a highly coarse-grained simulation algorithm for polymer nucleation. This has provided some encouraging comparisons with experiments. Nevertheless, an extended multiscale approach will be needed to simultaneously include the correct molecular physics, while also producing models that are sufficiently tractable for use in computational modelling of polymer processing. I will summarise current results and discuss methods of increasing the speed of barrier crossing simulations, along with techniques to map simulation algorithms on to non-stochastic models. Finally, I will also highlight some possible future methods to increase the physical detail of the underlying polymer nucleation model.	LT D
2pm 6th May	Dr. Kristian Franze, University of Cambridge "The mechanical control of neuronal growth in the developing brain" Abstract During the development of the nervous system, neurons migrate and grow over great distances. During these processes, they are exposed to a multitude of signals determining their growth velocities and direction. Currently, our understanding of neuronal development is, in large part, based on studies of biochemical signaling. Despite the fact that forces are involved in any kind of cell motion, mechanical aspects have so far rarely been considered. Here we used compliant cell culture substrates, traction force microscopy and calcium imaging to investigate how Xenopus neurons respond to their mechanical environment. Axonal growth velocities, directionality, fasciculation, i.e., their tendency to grow in bundles, and maturation all significantly depended on substrate stiffness. Moreover, when grown on substrates incorporating linear stiffness gradients, axon bundles were repelled by stiff substrates. In vivo atomic force microscopy measurements revealed stiffness gradients in developing brain tissue, which axons followed as well towards soft. Interfering with brain stiffness and mechanosensitive ion channels in vivo both led to similar aberrant neuronal growth patterns with reduced fasciculation and pathfinding errors, strongly suggesting that neuronal growth is not only controlled by chemical signals - as it is currently assumed - but also by the tissue's local mechanical properties.	F38
2pm 22nd April	Prof Matthew Turner, Warwick University "Ring polymers as a topological glass" Abstract Understanding ring polymers may be the last really hard unsolved problem in polymer theory. This is because of their fixed circular topology. Usually in polymer physics one can start by considering a one-chain description and then generalise to concentrated systems. Ring polymers, however, are required to remain unknotted and unlinked from their neighbours which makes the problem more difficult. We present some new results on Molecular Dynamics and Monte Carlo studies of concentrated systems of ring polymers. We propose the first method to identify inter-ring threadings, where one ring penetrates through another, and show how the slowing down of the dynamics of ring polymers is associated with the formation of a percolating cluster of such threadings. For long enough rings we suggest that this would constitute a novel state of matter that we describe as a topological glass. Finally we discuss how this might give us a new insight into the glass transition more generally, itself a notoriously difficult problem in condensed matter physics.	LT D
1pm 15th April	Dr Alastair Buckley, University of Sheffield "Solar Energy in Future Societies" Abstract Alastair will present research from EPSRC funded "Solar Energy in Future Societies" - a 4 year interdisciplinary project that is drawing to a close. The project concerns the roles and relationships of technology, public and communities in local energy generation and use. Results from a range of research approaches will be brought together to explain the complexities of the transition to distributed energy generation. These will include - local energy systems modelling; field performance data for Photovoltaic generation; approaches (and values) of public participation in local energy resource planning; and interdiscplinary research itself.	LT D
2pm 25th March	Prof James Durrant, Imperial "Correlating material's structure, charge carrier dynamics and device performance in organic solar cells." Abstract Organic solar cells based on polymer / fullerene blends are attracting extensive interest as a printable photovoltaic technology to lower the cost, and widen the applicability, of solar energy conversion. The function of these devices is based upon photoinduced charge separation in blend films of partially miscible donor polymers and fullerene acceptors. My talk will be focused upon the impact of blend morphology upon device performance. The first part of my talk will focus on the correlation between materials structure and device efficiency, including consideration of both pure and mixed domains, and the role of materials crystallinity in determining charge carrier energetics, and the impact of these structural considerations upon charge carrier separation and recombination dynamics. The second part of my talk will be concerned with device stability. I will first of all consider the role of materials crystallinity in determining polymer triplet state lifetimes and thereby influencing the stability of the polymer / fullerene blend to photodegradation in the presence of oxygen. I will conclude by considering the morphological stability of blend films upon thermal stress, and strategies to improve this stability through photoinduced cross-linking and other mechanisms.	LT D
12noon MONDAY 16th March	Suckjoon Jun, UC San Diego "Cell-size control and homeostasis at the single-cell level"	LT C
1pm Monday 9th March	Fred Combley Colloquium Prof Michael Kramer (Director, MPIfR Bonn) "100 years of General Relativity - was Einstein right?" Abstract This year, we celebrate the centenary of Einstein's theory of general relativity. When the theory was conceived, the number of experimental tests to confront the theory with was limited. Since then we have come a long way. In particular astronomical observations provide precision tests that were inconceivable even 50 years ago. We use neutron stars observable as pulsars to provide the most precise tests for strongly self-gravitating bodies, to prove that gravitational waves exist or to measure the effects of curvature of space time. We also attempt to determine the properties of black holes, such as their mass and spin to test the description of black holes within general relativity. One of the highlights will be an image of the "shadow" of the supermassive black hole in the centre of our Milky Way. Soon we also expect that gravitational wave detectors open up a new window to Einstein's Universe. In all cases, neutron stars or black holes play a crucial role. In this talk I will review some of the current and future tests of general relativity and compare those results with tests of alternative theories.	Arts Tower LT 4
2pm 25th February	Prof Tom McLeish FRS, Durham University "Global Low Frequency Protein Motions in Long-Range Allosteric Signalling" Abstract We present a foundational theory for how allostery can occur as a function of low frequency dynamics without a change in protein structure. Elastic inhomogeneities allow entropic 'signalling at a distance'. Remarkably, many globular proteins display just this class of elastic structure, in particular those that support allosteric binding of substrates (long-range co-operative effects between the binding sites of small molecules). Through multi-scale modelling of global normal modes we demonstrate negative co-operativity between the two cAMP ligands without change to the mean structure. Crucially, the value of the co-operativity is itself controlled by the interactions around a set of third allosteric "control sites". The theory makes key experimental predictions, validated by analysis of variant proteins by a combination of structural biology and isothermal calorimetry. A quantitative description of allostery as a free energy landscape revealed a protein 'design space' that identified the key inter- and intramolecular regulatory parameters that frame CRP/FNR family allostery. Furthermore, by analyzing naturally occurring CAP variants from diverse species, we demonstrate an evolutionary selection pressure to conserve residues crucial for allosteric control. The methodology establishes the means to engineer allosteric mechanisms that are driven by low frequency dynamics.	LTD
2pm 18th February	Dr Kislon Voïtchovsky, Durham University "Quantifying the behaviour of water and ions at soft interfaces: observations from atomic force microscopy" Abstract Water molecules and ions play a fundamental role in many biological phenomena from the folding and function of biomolecules to the local mechanical properties of biomembranes. These processes are partly controlled by the particular behaviour and dynamics of the liquid at the interface with the soft biomaterial. Experimentally, probing this 'interfacial liquid' locally and with nanoscale resolution is highly challenging and most results rely on theory and computer simulations. These difficulties can in principle be overcome with atomic force microscopy (AFM). Recent results on simple interfaces have demonstrated AFM's ability to map the molecular organisation of the interfacial liquid and gather quantitative information about its local dynamics. Here I present results showing how interfacial water can induce correlations between single metal ions at various soft and hard interfaces, create ordered ionic structures and alter the molecular dynamics at the interface. Preliminary findings suggest that similar effects occur at biointerfaces, hinting to intriguing possibilities for modulating the mechanical properties of biomembranes and charge transfer along natural and synthetic interfaces.	LTD
2pm Fri 6th February	Dr James Windmill, University of Strathclyde "Hearing in Nature: Models for creating new acoustic systems" Abstract In the world of engineering we utilise sound for many useful tasks, across a far larger range of frequencies than humans can hear. However, in Nature many different animals have evolved hearing systems which are sensitive to sounds outside our own capability. This includes a large variety of insects that have evolved to use sound for tasks such as communication and predator avoidance. The mechanisms used by other animals such as the insects are therefore a well of potential concepts and ideas for engineers to consider in seeking inspiration to solve acoustic problems. This talk will briefly look at recent work to investigate insect hearing systems, and discuss some examples of the unexpected characteristics found in insect ears. It will also discuss ongoing work on acoustic systems inspired by animal hearing, including that of the insects.	LTE
2pm 28th January	Dr James Sharp, University of Nottingham "Resonant vibrations of liquid and viscoelastic drops" Abstract The mechanical vibrational response of sessile (substrate supported) and levitated droplets can provide information about quantities such as the surface tension and viscosity of simple liquids. In the case of viscoelastic liquids, the vibrational frequencies and spectral widths of the mechanical resonances have a more complex dependence on surface tension and the frequency dependent rheological (elastic and viscous) properties of the drops. In this talk, I will describe recent experiments that use a simple optical deflection technique to measure the vibrational response of both liquid and viscoelastic droplets. I will discuss how the response of sessile drops depends upon their wetting characteristics (e.g. contact angle) and any anisotropy in drop shape. I will also discuss recently published results which describe how vibrations in levitated viscoelastic droplets can be used to probe the rheology of polymer solutions. In each case, the results will be interpreted in the context of a simple model which appears to capture the essential physics of droplet vibration.	LTE

2014

Date	Speaker & Title	Place
2pm 10th December	Dr Chris Powers, Zeiss "An introduction to the LSM 880 and the new Airyscan super-resolution technology" Abstract Discover the new LSM 880 with Airyscan from ZEISS - a new laser confocal scanning microsope that offers high sensitivity, improved resolution in x, y, z and high speed. LSM880 with Airyscan is the world's fastest linear scanning confocal microscope that will allow you to fully resolve highly dynamic processes, such as the movement of labelled proteins, all in one system. The majority of the talk will concentrate on the new Airyscan technology and explain how this technology will change the way in which laser scanning confocal microscopes will be manufactured in the future. The Airyscan technology gives two huge benefits: The first is that it enables super resolution imaging in a similar regime to the structured illumination microscopes but with all of the benefits of a traditional point scanning system. The second is that the Airyscan enables extremely sensitive image acquisition. The talk will be followed by tea/coffee/biscuits.	LT D
3pm 10th December	Prof Gail McConnell, University of Strathclyde "New methods and technologies for three-dimensional optical microscopy" Abstract As the life sciences community continues to embrace optical imaging, the growing range of applications places greater demands on the optical technology required. Robust and simple-to-use systems are needed to improve the efficiency and ease of existing imaging methodologies. My research involves the development and application of innovative optical systems to help address some of the fundamental challenges faced in biological imaging. I will present details of two current RCUK-funded research projects aimed at improving volumetric optical imaging. The first project involves the development of a super-resolution optical imaging method that does not require extensive computational power or specific fluorophores, and which can be performed with live cells and at speeds in excess of video-rate. The technique is possible using both laser scanning and wide-field imaging modes, and I will present results obtained from imaging healthy, aged and infected fluorescently-labelled erythrocytes. The second project concerns the creation of a new giant lens for laser scanning microscopy. Called the "Mesolens", this optical system allows a hundred-fold increase in the volume of the specimen from which sub-cellular detail can be obtained. Individual cells are seen in detail, but so also, for the first time, is their three-dimensional relationship to the whole organ or body. There is now strong worldwide interest because the benefit is obvious in the images already published. There are many applications that capitalise on the unique properties of the Mesolens, ranging from "super-high-throughput" analysis for large specimen single cell gel electrophoresis assays, sub-second mesoscopic imaging of live bioluminescent cells and sub-cellular fluorescence imaging of large thick specimens such are entire mouse embryos.	LT D
1pm 3rd December	Dr Andy Parnell, University of Sheffield "Identifying the structures responsible for structural colour in biological photonic materials" Abstract The vibrancy and variety of the colours and colour effects found in Nature has long been well-known; what has only recently been discovered is the sophistication of the physics that underlies these effects. Ground breaking work by Parker and Vukusic has emphasised the importance of structural colour – that is, colour that arises not primarily from dyes or pigments, but from diffraction effects from structures with periodic features on length scales commensurate with the wavelength of visible light. Studies by Vukusic et. al have shown that the brilliant white effect in the thin 5µm elytra layer of a Cyphochilus beetle is caused by the extensive internal scattering as a result of the internal structure of the scales, a disordered network of fibrils [1]. Recent work in the longhorn beetle has shown that the intense broadband reflection is alsoassociated with a structure of the kind that arises in spinodal decomposition [2]. My presentation will show some of our recent findings on these and a number of other other biologically optically active structures. 1. Vukusic, P.; Hallam, B.; Noyes, J., Brilliant whiteness in ultrathin beetle scales. Science 2007, 315 (5810), 348-348. 2. Dong, B. Q.; Zhan, T. R.; Liu, X. H.; Jiang, L. P.; Liu, F.; Hu, X. H.; Zi, J., Optical response of a disordered bicontinuous macroporous structure in the longhorn beetle Sphingnotus mirabilis. Physical Review E 2011, 84 (1).	LT D
2pm 19th November	Dr Mike Kaliteevski, Durham University "Tamm plasmons and optoelectronic devices on their basis" Abstract During the past few decades, the plasmonic properties of metallic nanostructures have received considerable interest in both fundamental and applied fields. Due to their ability to manipulate light at the nanoscale, these nanostructures are of great importance in many applications such as biosensing, surface-enhanced Raman scattering, and photonic circuits. Modern plasmonics are based on the physics of surface plasmons – the states of an electromagnetic field localized at the interface between a metal and dielectric – which are analogues of waveguide mode. Five years ago, a novel type of localized mode of the electromagnetic field (a Tamm plasmon) were predicted theoretically and subsequently demonstrated experimentally. Tamm plasmons (TP) are localized at the interface of a specially designed Bragg reflector and a metal and are the analogues to Fabry-Perot cavity modes. Tamm plasmons are very feasible to make: they can be obtained by depositing the metal film on top of Bragg reflector (which can contain some active media). The TP provides a very simple way of laterally localizing light in the semicoductor structures and are fabricated by basic photolithography without the need of etching through micrometer-scale thick multilayer structures. During the talk the basic physics of Tamm plasmon, and the review of of recent experimental results related to Tamm plasmon based microcavity structures (lasers, quantum light sources) will be provided.	LT D
2pm 12th November	Dr Mike Weir, University of Sheffield "Scattering studies of the structure of polymer nanocomposites" Abstract Graphene and other two-dimensional materials are excellent candidates as "filler" materials in nanocomposites, due to their extraordinary physical properties such as mechanical strength conductivity, both electrical and thermal. A successful polymer composite has the lightweight nature and processability of the host polymer material coupled with an enhancement in physical properties coming from the filler. We are working on polymer-graphene nanocomposites in the "Grapol" collaboration with Durham University and industrial partners. In this seminar I will explore the use of X-ray and neutron scattering techniques to examine the structures present in polymer-graphene nanocomposites. I will investigate the structure of the nanoparticle fillers as well as the effect of the nanoparticles upon the polymer chains themselves. I will show how selective deuteration may be used to label the individual polymer chains within the nanocomposite, and thus resolve distortions in the polymer material caused by introduction of the nanoparticle filler. From these results we hope to understand optimum formulations and processing conditions for our composites.	LT D
2pm 1st October	Dr Lisa Clark, University of Sheffield, Solar Farm "The Sheffield Solar Project and Performance of Solar PV Panels in the UK" Abstract Dr Lisa Clark from the Sheffield Solar project will introduce the Sheffield Solar project and give an overview of work undertaken within the team. On a basic level, Lisa will explain the data collated by the team and share research insights into real-world generation performance in the UK. The project encompasses two projects: a scientific test-facility on the roof of the Hicks Building (which comprises a range of photovoltaic technologies) and the microgeneration database, an online service to collect and analyse data from installation owners. This talk will discuss the variety of technologies on the market (including various silicon manufacturers and flexible thin film photovoltaics for lightweight integration into buildings) and will give up-to-date data on the actual generation across the country. This talk is aimed at a general audience, to introduce the project and the research undergoing in the department.	LT D
2pm 2nd September	Ricardo Henriques, UCL "A nanoscale view into cells through super-resolution microscopy" Abstract DNA, RNA and protein, part of the central molecules of biology, typically exist at dimensions of a few nanometers, well beyond the resolving power of conventional fluorescent microscopy (~300 nm). Super-resolution microscopy techniques hold to date the record in resolving power for light microscopy. These have both the capacity to differentiate and localize individual molecules at scales experimentally demonstrated of few nanometers (1-30 nm). In this family of methods, photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) as well as their variants embrace the potential to fully resolve complete cellular structures at the nanoscale, accurately localizing thousands to millions of individual fluorophores within a labeled cell. In this seminar I will introduce several of the aspects in super-resolution methods we have developed, ranging from analytical methods to novel super-resolution probes. Some of its applications will then be demonstrated by super-resolving host-pathogen interactions such as by HIV infection.	LT 6
2pm 26th August	Susan Cox, King's College London "Accelerating localisation microscopy" Abstract Localisation microscopy is a powerful tool for imaging structures at a lengthscale of tens of nm, but its utility for live cell imaging is limited by the time it takes to acquire the data needed for a super-resolution image. The acquisition time can be cut by more than two orders of magnitude by using advanced algorithms which can analyse dense data, trading off acquisition and processing time. We have developed two methods which allow different tradeoffs to be made. Modelling the entire localisation microscopy dataset using a Hidden Markov Model allows localisation information to be extracted from extremely dense datasets. This Bayesian analysis of blinking and bleaching (3B) is able to image dynamic processes in live cells at a timescale of a few seconds, though it is very computationally intensive, requiring at least several hours of analysis. Alternatively, a factor of ten improvement in analysis speed over the 3B method can be achieved by using a Gaussian Mixture Model, provided the data is not extremely high density. Our methods are demonstrated on various live cell systems, including cardiac myocytes and podosomes, showing a resolution of tens of nm with acquisition times down to a second. We also compare our methods to other high density algorithms and discuss the artefacts which can occur during reconstruction of the super-resolution image.	LT 6
11am 22nd August	Iwan Schaap, Göttingen, Germany "Mechanics of single biomolecules"	LT 6
3pm 25th June	Natsuhiko Yoshinaga, Tohoku University, Japan "Spontaneous motion and deformation of a droplet driven by chemical reaction" Abstract Spontaneous motion has been attracting lots of attention in last decades in nonlinear and nonequilibrium physics partially for its potential application to biological problems such as cell motility. Recently several model experiments showing spontaneous motion have been proposed in order to elucidate underlying mechanism of the motion. The systems in these works consist of relatively simple ingredients, for instance oil droplets in water, but nevertheless the results show rich motion and deformation of the droplet. Importantly, the system breaks symmetry and chooses one direction of motion. In this work, we theoretically derive a set of nonlinear equations exhibiting a transition between stationary and motile states starting from advection-reaction-diffusion equation driven away from an equilibrium state due to chemical reactions. A particular focus is on how hydrodynamic flow destabilizes an isotropic distribution of a concentration of chemicals. We also discuss a shape of the droplet. Due to self-propulsive motion and flow around the droplet, a spherical shape becomes unstable and it elongates perpendicular to the direction of motion. This fact would imply that the self-propulsion driven by chemical reaction is characterized as a pusher in terms of a flow field.	LT 6
3pm 14th May	Prof Sir Richard Friend, FRS, University of Cambridge "Organic Semiconductor LEDs and solar cells: delocalisation and spin" Abstract Pi-conjugated organic molecules and polymers now provide a set of well-performing semiconductors that support a wide range of devices, including light-emitting diodes (LEDs) as used in smart-phone displays, field-effect transistors (FETs) and photovoltaic diodes (PVs). These are attractive materials to manufacture, particularly for large-area applications where they can be processed by direct printing. The operation of organic semiconductor devices is very different to that of the well-known inorganics such as silicon. Their low dielectric constants give poor screening of Coulomb interactions so that electron-hole excitations are not free carriers but are strongly bound, as 'excitons'. This can give high luminescence efficiency as required in LEDs, but necessitates a 'donor' - 'acceptor' heterojunction structure to allow charges to separate from one another as required for photovoltaic operation. Strong Coulomb interactions cause large magnetic exchange interactions, splitting the energies spin singlet and spin triplet excitons. Schemes to control these spin states are now being actively developed and offer novel routes to high efficiency solar cells.	LT 1
3pm 7th May	Dr Ard Louis, University of Oxford "Modelling DNA: nanotechnology and biophysics" Abstract DNA nanotechnology is a rapidly growing area of research, opening up the possibility to create large and complex dynamics structure by self-assembly. To understand the basic biophysics of these novel systems requires new theoretical tools. We have been developing a coarse-grained model for DNA, OxDNA (dna.physics.ox.ac.uk) that can be applied to static and dynamic nanostructures, including DNA origami, a DNA walker and DNA tweezers. It can also be used to study basic biophysical processes that occur when DNA is twisted and pulled.	LT 6
3pm 30th April	Dr Cecile Perrault, University of Sheffield, Mechanical Engineering "Mechanobiology and Cellular Mechanics" Abstract Mechanobiology is an emerging field of science at the interface of biology, physics and engineering. It focuses on the way that physical forces and changes in cell or tissue mechanics contribute to development, physiology, and disease. A major challenge in the field is understanding mechanotransduction--the molecular mechanism by which cells sense and respond to mechanical signals. While medicine has typically looked for the genetic basis of disease, advances in mechanobiology suggest that changes in cell mechanics, extracellular matrix structure, or mechanotransduction may contribute to the development of many diseases, including atherosclerosis, asthma, osteoporosis, heart failure, and cancer. There is also a strong mechanical basis for many generalized medical disabilities, such as lower back pain. In our laboratory, we study mechanobiology at the cellular level in order to better understand how forces can influence cellular behaviour, drive stem cell differentiation and improve medical devices. Our set of tools also allow us to look at the larger scale and to tackle the multiscale challenge of biomechanics, bringing information from the cellular level into the tissue and organ scale.	LT 6
3pm 23rd April	Prof Dek Woolfson, University of Bristol "Protein design and assembly across scales: from nanopores and cages to fibres and hydrogels" Abstract We have developed a toolkit of de novo peptides (1). These can be used as building blocks for the rapid construction of new protein structures and supramolecular assemblies. This talk will demonstrate the utility of this approach to make nanoscale protein pores (2), nanocages (3), and protein fibres and hydrogel (4). Potential applications of the structures and materials achieved span nanoscience, synthetic biology and biotechnology. 1. A Basis Set of de Novo Coiled-Coil Peptide Oligomers for Rational Protein Design and Synthetic Biology. JM Fletcher, AL Boyle, M Bruning, GJ Bartlett, TL Vincent, NR Zaccai, CT Armstrong, EHC Bromley, PJ Booth, RL Brady, AR Thomson, and DN Woolfson ACS Synthetic Biology 6, 240-250 (2012) 2.A de novo peptide hexamer with a mutable channel. NR Zaccai, B Chi, AR Thomson, AL Boyle, GJ Bartlett, M Bruning, N Linden, RB Sessions, PJ Booth, RL Brady and DN Woolfson Nature Chemical Biology 7, 935-941 (2011) 3.Self-assembling cages from coiled-coil peptide modules. JM Fletcher, RL Harniman, FRH Barnes, AL Boyle, A Collins, J Mantell, TH Sharp Antognozzi, PJ Booth, N Linden, MJ Miles, RB Sessions, P Verkade, and DN Woolfson Science 340, 595-599 (2013) 4.Rational design and application of responsive alpha-helical peptide hydrogels. EF Banwell, ES Abelardo, DJ Adams, MA Birchall, A Corrigan, AM Donald, M Kirkland, LC Serpell, MF Butler, and DN Woolfson Nature Materials 8, 596-600 (2009).	LT 6
3pm 9th April	Dr Natalie Stingelin-Stutzmann, Imperial College London "Solution processed inorganic/organic photonic structures of low loss and tunable refractive index for use in optoelectronic devices" Abstract An ever increasing interest in the development and application of innovative optical and optoelectronic devices places greater emphasis for the advancement of new smart and functional materials that are readily processable. Significant progress has already been realised in the fields of organic light-emitting diodes (OLEDs) and photovoltaic cells (OPVs) through development of novel semiconducting materials. Further developments in these areas are turning to the deployment of photonic structures to aid and improve light management in these systems, e.g. input-/output-coupling, enhanced absorption and waveguiding. In this work, results from a novel class of hybrid material systems that offer an outstanding set of optical and material properties, including tunable refractive index, low optical losses and solution process ability, are presented. We show that the attributes of these novel hybrid material systems can be controlled and manipulated by a range of means that include 'alloying' or suitable post-deposition treatments, such as thermal annealing and/or irradiation with UV-light. As a consequence, these hybrid materials can exhibit refractive indices of up to 2.1 while also being highly transparent over the entire visible, near- and mid- infrared (N-IR, M-IR) wavelength regime [1]. Furthermore, the processing properties allow the realisation of solution-based, optically low-loss photonic structures that are straightforward to implement in structures, such as OPVs. Given that the readily achievable nature of high quality optical properties and the exceptionally low loss from a single high-index up to several microns thick have already been demonstrated, the focus is here turned to the further development of this generic class of hybrid materials, which are based on metal oxide hydrates and bulk commodity polymers such as poly(vinyl alcohol). To this end, we highlight our recent efforts in introducing different metals, culminating in the successful development of mixed-metal oxide hydrate hybrid materials. [1] M. Russo et al, J. Polym. Sci., Part B: Polym. Phys. 50(1), 65, (2011).	LT 6
3pm 2nd April	Dr Richard Thompson, University of Durham, Dept of Chemistry "Cookery" for thin Polymer Films Abstract Self-organisation in thin multi-component polymer films is vital to their physical properties, e.g conduction, adhesion, wettability etc. In the simplest case, films are cast from solution and/or annealed above the glass transition or melting point (baked) to equilibrium. In recent years, more sophisticated methods such as solvent vapour annealing (steaming?) have emerged to control the final distribution of the components. Alternative treatments, analogous to poaching, pickling and deep-frying will be presented alongside a "salad option". Ion beam analysis and neutron reflectivity allow the concentration versus depth profile, and the influence of the solvent treatment on the polymer-solvent interface to be determined. Understanding these parameters can guide the choice of processing method to obtain a particular film structure. [pdf file abstract]	LT 6
3pm 12th March	Prof Martin Howard, John Innes Centre "How cells get to be the right size and put things at the right place inside them" Abstract In this talk I will discuss two problems, which surprisingly turn out to be connected. The first is how fission yeast cells control their size. I will propose a theory that explains how this can be performed via an effective measurement of the plasma membrane surface area. Predictions from this theory are then successfully tested. The second problem is how low copy number plasmids in bacteria are equally spaced throughout the cell, thereby leading to equal partitioning at cell division. I will present a simple mechanism based on competitive pulling that can explain this phenomena and which has again made experimentally verified predictions.	LT 6
4pm 5th March	Prof I. M. Dharmadasa (Dharme), Sheffield Hallam University "Next generation thin film solar cells based on graded bandgap devices utilising materials with columnar type grains grown by electroplating" Abstract Low cost electroplating has been used to deposit thin layers of ZnS buffer layers, CdS window layers and narrow bandgap CdTe absorber material. These layers were fully characterised for their structural, optical, electrical and morphological properties using X-ray diffraction (XRD), X-ray fluorescence (XRF), Raman, optical absorption, photoelectro-chemical (PEC) cell, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and 3D atomic force microscopy (AFM). Material characterisation reveals that the window materials grown on glass/FTO substrates consist of uni-directional, normal to the substrate and compact nano-rods (see Figure 1a) and the absorber material grown on glass/FTO/CdS consists of rods or columnar-shaped grains with larger grains (see Figure 1b). Fully processed glass/FTO/buffer layer/window layer/absorber layer/metal, structures show varying photovoltaic parameters exhibiting up to 10.4% conversion efficiencies with V_oc ≈ 640 mV, J_sc ≈ 40.8 mAcm^-2 and FF ≈ 0.40 (Figure 1c). The excessively large J_sc values arise due to existence of rod-type material structures in nano-scale and low FF values arise due to the same reason. Leakage paths are readily formed due to the rod- shaped structures existing normal to the substrate, and these should be able to be blocked with appropriate methods in order to avoid this detrimental process reducing FF (see Figure 2). Work is progressing to improve reproducibility of device processing and the results to date are reported in this presentation. [pdf file abstract]	LT 6
3pm 26th February	Dr Sarah Staniland, University of Sheffield, Dept of Chemistry "From biomineralisation in magnetic bacteria to the biomimetic synthesis of magnetic nanoparticles and arrays" Abstract Magnetic nanoparticles have a vast range of applications in both nanotechnology and biomedicine. Magnetic bacteria produce magnetic nanoparticles by taking up iron ions from solution and precipitating precisely formed magnetite nanoparticles within an internal liposomes in their cell termed a magnetosome. In this talk I explore how we can utilise the magnetosomes and enhance them in vivo as well as consider biomimetic approached to precipitate magnetic nanoparticles in vitro. We will explore how proteins within the magnetosome membrane are responsible for particle formation and how these can be utilised to develop nanoscale architectures and arrays for future applications.	LT 6
3pm 19th February	Dr Sarah Harris, University of Leeds "Computer Simulations of Biological Macromolecules - Dynamics, Defects and Disorder" Abstract Computational models have huge potential to provide insight into molecular biology by providing detailed animations of biomolecules and their interactions. Molecular simulation can show not only how the shapes of biomolecules change due to their thermal motion, but also how the structure of individual biomolecules is affected by subjecting them to mechanical stress. We use atomistic molecular dynamics simulation to investigate the structural and dynamic implications of DNA packing through supercoiling, and have shown that sufficiently high levels of torsional stress can induce structural transitions in DNA that may be of biological relevance. We have also developed a new algorithm that uses continuum mechanics to model biomolecules that are too large to be simulated at the atomisic level. These calculations emphasise the importance of dynamics, defects and disorder in biomolecules to our understanding of their mechanism of action in vivo.	LT 5

2013

Date	Speaker & Title	Place
3pm 11th Dec	Dr Mike Smith, University of Nottingham "Interfacial constraints in colloidal fluids" Abstract Colloidal fluids (0.1-10μm particles suspended in a liquid) represent an apparently simple system with many real world examples: toothpaste, glazes, ceramics. For many of these systems interfaces, either solid-liquid or liquid-gas have an important role e.g ink drying on paper. In this talk I will present two different problems in which modifying the nature of the constraining interface is shown to play an important role. Firstly, I discuss the drying of a film of particles, a process which is strongly akin to, for example, paint drying. Upon drying, stresses build up in the film leading to the formation of cracking patterns. Through manipulating the strength of constraint provided by the substrate we show that these crack patterns can be altered, revealing some of the underlying physics involved in film formation [1]. Secondly, I examine the extensional rheology of a concentrated colloidal suspension. Rheological measurements are often performed using shear rheology in which the fluid is largely enclosed between two solid boundaries. However, I will show that by changing the geometry to one in which the majority of the surface area consists of a liquid-gas interface a number of important differences immerge [2]. [1] M.I. Smith, J.S. Sharp, Langmuir 27, 8009-8017 (2011) [2] M.I. Smith, R. Besseling, M.E. Cates, V. Bertola, Nature Communications 1:114 (2010)	L.T.D.
3pm 4th Dec	Dr Chris Holland, University of Sheffield (Materials Science and Engineering) "Understanding the secret of a spider's success" Abstract If we wish to mimic or copy silk we must first understand it. Understanding means not only knowing the relevant proteins but also knowing their function and, importantly, their structure - property relationships. Silks are biological polymers that have evolved to be processed by controlled protein denaturation, a process with many similarities to flow induced polymer crystallisation. But to date no one has succeeded in spinning these proteins into anything resembling the natural fibre neither in its microstructure (which is rather complex) nor in its mechanical properties (which are outstanding). Why is this still the case, and what challenges remain? This talk will propose that silks are a unique source of inspiration for the current challenges facing the synthetic polymer industry, provided we understand how to process them correctly. I will provide an overview of Natures 400 million years of R&D into silk and our recent studies into the importance of processing in this fascinating material alongside some potential future applications of high tech silk based products.	L.T.D.
3pm 27th Nov	Dr Teuta Pilizota, University of Edinburgh "Origins of E. coli growth rate and cell shape changes at high external osmolarity" Abstract In Escherichia coli, a sudden increase in external concentration causes a pressure drop across the cell envelope, followed by an active recovery. However, post recovery E. coli cells have been shown to grow slower, smaller in volume and at a reduced turgor pressure. Despite the fact that the active recovery is a key stress response, the nature of these changes and how they relate to each other, as well as to other growth modulating conditions, is not understood. It was shown recently that turgor pressure is not required for the bio synthesis of E. coli's cell wall. However, it was also indicated that the correct attachment of the inner membrane and cell wall, which can be severely disrupted during osmotic shocks and plasmolysis, might be. During the talk I will show, using fluorescence imaging of single cells during hyperosmotic shocks, combined with custom made microfluidics, that cells fully recover their volume to initial value and continue to grow slower immediately after the recovery, with no observed pause. I will show that cell envelope material properties do not change after hyperosmotic shock, and that at the point of full volume recovery cell shape changes only slightly. I will conclude that turgor pressure recovers to the initial value as the volume does, despite the fact that is not directly needed for cell wall biosynthesis. Previously observed reduction in turgor pressure at higher osmolalities must therefore occur at a later time point, and is not responsible for the changes in growth rates. I will propose that turgor pressure is used as a feedback variably for osmoregulatory pumps, and that re-establishing it to initial value ensure correct inner membrane and cell wall attachment needed for cell wall bio synthesis. At the end of the talk I will also show that growth modulation is a temporary adaptation and that cells transferred back to lower osmolalilty resume growth at the initial growth rate even after several generations in high osmolality environments.	L.T.D.
3pm 20th Nov	Prof Ravi Silva, University of Surrey "The Carbon Age: Moving Nano-Carbons from Science to Technology" Abstract Recent developments in solution processable single junction polymer solar cells have led to a significant improvement in power conversion efficiencies from ~5% to beyond 9%. While much of the initial efficiency improvements were driven through judicious design of donor polymers, it is the engineering of device architectures through the incorporation of inorganic nanostructures and better processing that has continued the efficiency gains. Inorganic nano-components such as carbon nanotubes, graphene and its derivatives, metal nanoparticles and metal oxides that have been central role in improving device performance and longevity beyond those achieved by conventional 3G polymer solar cells. The present work aims to summarise the diverse roles played by the nano-systems and features in state of the art next generation (4G) polymer solar cells. With novel synthesis routes for nano-carbon production now available, the next chapter in the story of carbon technology is also ready to be written. Within this talk I will discuss how large area low temperature growth of carbon nanotubes can be applied to technologies including: CMOS applications, energy, and biological applications. The challenges associated with the engineering of such devices for future deployment are also discussed.	L.T.D.
3pm 6th Nov	Dr Pietro Cicuta, University of Cambridge "Physical Organization and Dynamics of the Bacterial Chromosome" Abstract In bacteria, chromosomal architecture shows strong spatial and temporal organization, and regulates key cellular functions, such as transcription. Tracking the motion of chromosomal loci at short timescales provides information related to both the physical state of the nucleo–protein complex and its local environment, independent of large-scale motions related to genome segregation. We have investigated the short-time (0.1–10 s) dynamics of ﬂuorescently labelled chromosomal loci in Escherichia coli cultured at different growth rates. At these timescales, we observe for the ﬁrst time a dependence of the loci’s apparent diffusion on both their subcellular localization and chromosomal coordinate, and we provide evidence that the properties of the chromosome are similar in the tested growth conditions. These results indicate that either non-equilibrium ﬂuctuations due to enzyme activity or the organization of the genome as a polymer–protein complex vary as a function of the distance from the origin of replication.	L.T.D.
3pm 30th Oct	Dr Buddhapriya Chakrabarti, Durham University "Physics of curling ribbons: Elastodynamics in two contexts, foam micromechanics and ribbon curling" Abstract Imagine holding a ribbon between a blade and your thumb and running it along its length. Florists often use this to form helical bows to wrap bouquets. What determines its shape, which face does it curl on and what determines its handedness. Using a combination of experiments and theory I will explain the process of ribbon curling quantitatively. My second example will focus on micromechanics of foam in particular foam degradation when subjected to periodic forcing. Using a combination of experiments and theory we provide cues for better designing cushioning materials that maximizes dissipation and minimizes degradation.	L.T.D.
3pm 23rd Oct	Internal seminar: New people introduce themselves	F28
3pm 5th June	Prof Maria Garcia-Parajo, ICFO The Institute of Photonic Sciences, Barcelona "Nanoscale imaging and spectroscopy of living cell membranes using single molecule optical nanotools" Abstract A hot topic in current cell biology is to understand the specific nanometer-scale organization and distribution of the surface machinery of living cells and the role that these molecular properties play in the spatiotemporal control of different cellular processes. A great deal of novel knowledge in this area is currently being generated thanks to the advent of modern superresolution optical techniques combined with single molecule approaches. In particular, near-field optical nanoscopy (also known as NSOM) is particularly well suited for the study of biological cell surfaces at the nanometer scale [1]. Moreover, nanophotonic approaches and dynamic measurements in ultra-confined volumes allow nowadays the visualization of dynamic processes on cell membranes with optical spatial resolution down to 30 nm and sub-millisecond time resolution [2]. In this contribution, I will review most recent technological advances on near-field nanoscopy, specifically in the field of optical nano-antennas to allow for ultrasensitive detection, nanoimaging and nanospectroscopy of biomolecules in living cells [3,4]. Furthermore, I will discuss how these approaches are now exploited to reveal the existence of pre-assembled nanoplatforms of multi-molecular components on mammalian cells [5,6]. Our final aim from the biological point of view is to understand the molecular mechanisms responsible for the well-defined architecture of the cell surface and to decipher the molecular bases of diverse cellular processes, ranging from cell adhesion to pathogen recognition. 1. P. Hinterdorfer at el, Acc. Chem. Res. 45, 327-336 (2012). 2. C. Manzo et al Biophys. J. 100, 2, (2011). 3. M. Mivelle et al Nano Lett. 12, 5972-5978 (2012). 4. D. Punj et al, Nature Nanotech, in press. 5. T.S. van Zanten et al PNAS 107, 15437, (2010). 6. T.S. van Zanten et al PNAS 106, 18557, (2009).	F20
3pm 15th May	Dr Emma Helm, University Hospitals Coventry & Warwickshire "Advanced Analysis Techniques for Assessment of the Lungs on CT - A Radiologist's Perspective" Abstract Currently, no in vivo technique can match CT imaging of the lungs in terms of spatial resolution. However, routine clinical analysis of CT scans does not usually extend beyond visual interpretation of individual lung slices. In recent years, a number of computerised analysis techniques have been developed to automatically analyse the large datasets generated by each CT examination of the lungs. These include density analysis, texture analysis and automated detection of a number of specific pathologies. This talk will examine the current limits of our analysis and will look at emerging techniques, particularly with reference to analysis of interstitial lung disease, a condition which leads to progressive scarring and shrinkage of the lungs.	F20
12pm 22nd May	Dr Chris Groves, Durham "Loss mechanisms in Organic Solar Cells" Abstract Organic solar cells (OSCs) are a promising technology to reduce the cost of renewable energy because they can be made, in principle at least, cheaply and scalably. Significant progress has been made since the first reports of OSCs with current devices nearing 10% efficiency, which is seen as a landmark for commercial viability. However, this progress has been largely achieved by intuition and trial-and-error, and much of the operation of OSCs is still under debate. Part of the difficulty in understanding OSCs better is relating processes that occur on the nanoscale to macro-scale measured quantities. Monte Carlo modeling techniques are one method by which these links can be made. This talk will review findings of Monte Carlo models which in particular focus on losses in OSCs. It will be shown that, counter to expectation, efficient charge generation can be obtained without the commonly quoted 'optimum' morphology with pure domains of ~20nm, and that instead the first few nanometers in the region of the donor-acceptor interface largely determine the degree of geminate recombination. Furthermore, it will be shown how bulk and surface morphology can influence non-geminate recombination. More generally the talk will highlight the benefits of soft and condensed matter physicists working together to determine both the structure and function of organic electronic devices.	F20
3pm 24th April	Dr Otti Croze, University of Cambridge "The active dispersion of swimming bacteria and algae" Abstract Many microorganisms swim in directions biased by environmental cues. A well-studied example is the directed motion of the bacterium E.coli up (down) nutrient (poison) gradients (chemotaxis). Swimming algae have also evolved 'taxes'. For example, bottom-heavy algae are biased by a gravitational torque to swim upwards (gravitaxis). In flows, a viscous torque also acts on a swimmer, biasing it to swim to low shear regions (gyrotaxis). Such biases lead to surprising collective behaviour: gyrotactic swimmer suspensions are hydrodynamically unstable, breaking up into stunning patterns. Populations of chemotactic bacteria also make beautiful patterns: in soft nurtient gels they migrate as concentric rings. Many biotechnological applications involve suspensions of microorganisms in porous substrates (e.g. soil) or flowed within conduits (e.g. photobioreactors). The efficiency of these technologies depends on our ability to predict suspension behaviour. The biased swimming of many useful organisms is not considered in engineering models. Inspired by this, I have investigated the dispersion of chemotactic bacteria in porous gels and that of gyrotactic algae in pipe/channel by modelling and experiment. I will show how active dispersion of swimmers can be very different from that of passive particles (e.g. molecules or colloids). Finally, I will discuss the implications of my findings for air-lift bioreactor operation and algal-bacterial symbiosis.	F20
3pm 17th April	Dr Bart Hoogenboom, London Centre for Nanotechnology UCL "Nanoscale imaging and modelling of soft biomolecules" Abstract Atomic force microscopy (AFM) is a unique tool in combining nanometre spatial resolution and high temporal resolution with the ability to visualise biological molecules in their native environment, i.e., aqueous solution. Its ultimate resolution on such samples depends on the strength of the interaction between the sample and the AFM probe: Too weak an interaction means low contrast, too high an interaction usually results in molecules being distorted or dislodged. I will discuss our recent work on minimising the invasiveness of AFM in liquid, resulting among others in the first observation of the DNA double helix on a single molecule in aqueous solution [1]. In another application, we deliberately indent the sample to obtain subsurface structural information of large protein assemblies such as the nuclear pore complex. The AFM data agree well with the pore structure obtained by cryo-electron microscopy, and enable us, in addition, to compare the nanomechanical properties to different in-silico scenarios [2] for the selective transport through this macromolecular machine. [1] Nano Lett. 2012, 12(7), 3846-3850. [2] Phys. Rev. E 2012, 85(6), 061917.	F20
2pm 20th March	Dr Raphaël Voituriez, Université Pierre et Marie Curie, Paris "First-passage statistics and search strategies" Abstract How long does it take a "searcher" to reach a "target" for the first time? This first-passage time is a key quantity for evaluating the kinetics of various processes, and in particular chemical reactions involving "small" numbers of particles such as gene transcription, or at larger scales the time needed for animals to find food resources. I will present recent results which enable the evaluation of the distribution of first-passage time for a wide range of random search processes evolving in a confined domain. This approach reveals a general dependence of the first-passage time distribution on the geometry of the problem, which can become a key parameter that controls the kinetics of the search process. I will show how these results apply to transport in disordered and fractal media, and highlight their implications in transcription kinetics and other search processes at larger scales.	F20
3pm 6th March	Prof Alexei Nabok, Sheffield Hallam University "Optical method of ellipsometry for chemical and bio-sensing" Abstract As an introduction, I'll briefly outline research activities of our research group in the area of organic films and chemical-(bio-)sensing. The main focus of my talk is on optical bio-sensing, particularly on the methods utilising phase detection such as ellipsometry. The principles of spectroscopic ellipsometry, and total internal reflection ellipsometry in particular, will be outlined. Several case studies in bio-sensing will be discussed including the detection of low molecular weight molecules such as toxins (mycotoxins, pesticides, herbicides, alkylphenols, etc.), the optical study of DNA hybridisation, detection Alzheimer's disease markers. In conclusion, I'll mention several possibilities of further development of optical phase methods. Slides	F20
**4pm** 27th Feb	Dr Ahmed Iraqi, Dept of Chemistry, University of Sheffield "Low energy gap polymers for application in solar cells" Abstract Research into the use of conjugated polymers for application in bulk heterojunction solar cells has been the subject of much interest in recent years in view of their potential technological value for energy generation. Major advances have been achieved in this area; however, new polymer systems with high absorption coefficients, extended absorption spectra and adequate energy levels for use as electron donors to fullerene molecular acceptors are still being sought in this area. In this presentation, we will report the preparation and characterization of number of low energy gap donor acceptor alternating copolymers developed at Sheffield. We will also present studies on the physical properties of the polymers and their ability to act as electron donors to PCBM as well as their performance in bulk heterojunction solar cells.	**L.T.B**
3pm 13th Feb	Dr Davide Marenduzzo, University of Edinburgh "Modelling the spatial organisation of DNA-protein systems, and of eukaryotic chromosomes" Abstract While we now know in details the sequence of most eukaryotic genomes, we still have only a rudimentary idea of how these genomes fold in space, or how structure affects function. In both pro- and eukaryotes, DNA is invariably associated with a number of proteins, such as histones, polymerases, transcription factors etc. Rather than merely using DNA as a track on which to diffuse around or move along, these proteins often profoundly change the 3-dimensional structure of the genome. I will show results from Brownian dynamics simulations of DNA and DNA-binding proteins which lead to a number of patterns, some of which may be relevant in vivo. If time permits, I will also present a coarse grained molecular dynamics study of chromosome 14, comparing the structure we obtain in simulations with the contacts found by our experimental collaborators via fluorescence in situ hybridization (FISH) and chromosome conformation capture (3C) experiments.	F20
3pm 6th Feb	Prof Tim Newman, University of Dundee "Approaching biology discretely" Abstract The idea that physical systems are deterministic, and codified by differential equations, has been extraordinarily useful in understanding supra-atomic phenomena. This idea, whether imposed deliberately or not, has underlain much of the theoretical modeling of living systems. I will argue that a fundamentally non-deterministic approach to biology is typically more appropriate. Such probabilistic thinking naturally places more importance on the discreteness of living systems and their components, which in turn raises interesting questions about the relative explanatory power of emergence versus regulation in biology. I will temper the philosophical tenor of this talk by presenting in detail two examples of discrete modeling, which have uncovered surprising new insights in the well-studied problems of cancer metastasis and biochemical oscillations.	F20
3pm 30th Jan	Dr Jon Howse, Dept of Chemistry & Biological Engineering, University of Sheffield "(i) Development of real-space imaging techniques for the study of phase separation in polmyer blends & (ii) Combining Neutron Reflectivity with Attenuated Total Reflection FTIR to study of polyelectrolyte brushes at the solid liquid interface." Abstract Part (i) Spin coating is commonly used to make thin films of high uniformity over large surface areas. As a research tool it is widely used to make component layers in conductive polymers systems for light emitting diodes as well as polymer based photovoltaics. The final performance of such devices depends greatly upon the morphology of the film, in particular the interface between components. When blends of polymers are spun from a single solution a rich variety of phase separated morphologies results which affect the device performance. Control over this process, determined from a better understanding of this process therefore allows for significant device improvements to be realised. Spin coating by its very nature is a fast process both temporally and physically due to the rotation of the sample, and to-date, only reflection interference(1) and scattering studies(2) have been made, both of which only sample an average of the surface have been possible. Modern advances in LED technology and triggering, and the sensitivity of electron-multiplier-charged coupled devices (EMCCD) now allow for the direct observation of this process and we have applied this for the in-situ observation of phase separation in polymer blends. Our results provide direct, irrefutable evidence for the evolution of the final morphologies that result from these blends and coupled to parallel laser scattering experiments we are able to understand and visualise this fast, non-equilibrium process with previously unseen detail. The use of near-monochromatic light also allows for the determination of the rate of thinning through interference effect and coupled with ellipsometry and atomic force microscopy (of the final film) the 3D topography of the film can be reconstructed for all stage of the spin-coating process. Part (ii). Silicon is optically transparent to much of the Infra-red spectrum and also to thermal neutrons. This makes it a great substrate for attenuated total internal reflection FTIR and also neutron reflectivity experiments. I will briefly discuss our recent experiments where we have created a solid-liquid cell which allows for simulatanous measurements of both IR spectra and neutron reflectivity. We have applied this approach for the study of polyelectrolyte brushes at the solid/liquid interface which undergo chemical and morphological changes as a function of pH. From the IR data we can observe the chemical changes in the brush and from the neutron data we are able to observe the polymer brush profile. 1. D. P. Birnie, Journal of Non-Crystalline Solids 218, 174 (Sep, 1997). 2. S. Y. Heriot, R. A. L. Jones, Nature Materials 4, 782 (Oct, 2005).	L.T. E
3pm 23rd Jan	Prof Steve Armes, Dept of Chemistry, University of Sheffield "Polymerisation-Induced Self-Assembly" Abstract Methacrylic diblock copolymers are prepared via reversible addition-fragmentation chain transfer (RAFT) chemistry at 70oC using an aqueous dispersion polymerization formulation. The first block is water-soluble poly(glycerol monomethacrylate), whereas the second block comprises water-insoluble poly(2-hydroxypropyl methacrylate). As it grows, the latter block becomes increasingly hydrophobic, which drives in situ self-assembly to form spherical nanoparticles of 25-100 nm diameter at 10% solids. Adjusting the copolymer curvature enables the morphology to be varied systematically from spheres to worms to vesicles. Phase diagrams are elucidated, which allows the reproducible synthesis of nanoparticles with predictable morphologies at up to 25% solids. If vesicles are targeted, the block copolymer morphology evolves from spheres to worms to vesicles during the polymerization. TEM studies reveal jelly-fish nano-structures that provide mechanistic insights regarding the worm-to-vesicle transition. The worm phase leads to shear-thinning, free-standing gels at 20oC but degelation occurs on cooling to 5oC due to a reversible worm-to-sphere transition. Thus these worm gels can be readily sterilised via cold ultrafiltration. It is also shown that the basic principles of this 'polymerisation-induced self-assembly' approach are generic: a range of diblock copolymer nano-objects can be readily prepared in ethanol (and other organic solvents) as well as water. Various applications are being explored for this platform technology.	F41
3pm 16th Jan	Dr Jeremy Craven, Molecular Biology and Biotechnology, University of Sheffield "The fungus that cases "thrush" invades tissue by putting out "hyphal tubes" (just like most other fungi). This is a great system for trying to bring together molecular cell biology detail and basic physics and geometry in a 3D kinetics model. How far can we get?"	L.T. D

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