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Bristol Biodesign Institute WELCOME Bristol BioDesign Institute Biomolecules to biosystems from understanding to design The Bristol BioDesign Institute (BBI) is one of the University of Bristol’s Specialist Research Institutes. The BBI brings together BrisSynBio, a UK Synthetic Biology Research Centre, the SynBio Centre for Doctoral Training, our Innovation Programme and Public Engagement activities. With wide-ranging applications from health to food security, BBI combines pioneering synthetic biology approaches with understanding biomolecular systems to deliver the rational design and engineering of biological systems for useful purposes. This is delivered through multidisciplinary research which brings together postgraduate and postdoctoral researchers, academics, policy makers and industry, whilst also engaging the public with emerging solutions to global challenges. The BBI places the University of Bristol among the forerunners of UK and international synthetic biology and biodesign research, teaching and innovation. Director: Professor Dek Woolfson Co-Directors: Professor Imre Berger Professor Claire Grierson Professor Mario di Bernardo Conference organising committee: Imre Berger, BrisSynBio Director and Bristol BioDesign Institute Co-Director Graham Day, PhD Student, School of Cellular and Molecular Medicine Bethany Hickton, PhD student, School of Cellular and Molecular Medicine Kathleen Sedgley, Bristol BioDesign Institute Manager Mark Winfield, Post-doctoral Research Assistant, School of Biological Sciences Marie Woods, Bristol BioDesign Administrator Dek Woolfson, BrisSynBio PI and Bristol BioDesign Institute Director Ioannis Zampetakis, PhD Student, Department of Aerospace Engineering Image: Claudia Stoker, Vivid Biology 1 CONTENTS Contents Bristol BioDesign Institute................................................................................................................... 1 PLENARY PRESENTATIONS Dr Paul Race School of Biochemistry, University of Bristol ................................................................ 4 Professor Katharina Landfester Max Planck Institute for Polymer Research, Mainz, Germany ........ 5 PUBLIC LECTURE Professor Nadrian Seeman New York University ................................................................................ 6 ORAL PRESENTATIONS On-demand gene expression patterning and signalling pathway activity in mammalian cells .......... 8 Designing genomes using a computational design-build-test cycle ................................................... 9 Protein design in the cell: De novo bacterial cytoscaffolds .............................................................. 10 How molecular modelling can support synthetic biology, and vice versa ........................................ 11 Investigating lanthanide binding to designed coiled coil trimers ..................................................... 12 vSAGE: self-assembled peptide cages presenting immunogenic peptides and proteins as a vaccine delivery system ................................................................................................................................. 13 Fabricating an extracellular matrix analogue using natural polymers for cartilage tissue engineering applications ................................................................................................................... 14 Using bacterial adhesins to direct human stem cells to the myocardium........................................ 15 Out of equilibrium protocell systems ............................................................................................... 16 Molecular membrane engineering for nanoreactors ....................................................................... 17 POSTER PRESENTATIONS 18 Poster abstracts…………………………………………………………………………………………………………………….19 - 53 2 PROGRAMME 08:30 onwards Registration East foyer, School of Chemistry Opening session Chair: Imre Berger, Director, BrisSynBio 09:00 – 09:05 Dek Woolfson Opening remarks 09:05 – 09:15 Hugh Brady Vice Chancellor and President, University of Bristol 09:15 – 10:15 Paul Race, Opening plenary University of Bristol Kill or cure: Repurposing bacterial adhesins for therapeutic payload delivery 10:15 – 10:35 Elisa Pedone On-demand gene expression patterning and signalling pathway activity in mammalian cells 10:35 – 10:55 Joshua Rees Designing Genomes using a Computational Design- Build-Test Cycle 10:55 – 11:30 Coffee and posters East foyer Session 1: Design Chair: Professor Claire Grierson 11:30 – 11:50 Lorna Hodgson Protein design in the cell: De novo bacterial cytoscaffolds 11:50 – 12:10 Eric Lang How molecular modelling can support synthetic biology, and vice versa 12:10 – 12:30 Oliver Daubney Investigating lanthanide binding to designed coiled coil trimers 12:30 – 13:50 Lunch and posters East foyer Session 2: Medical applications Chair: Dr Lucia Marucci 13:50 – 14:10 Caroline Morris vSAGE: self-assembled peptide cages presenting immunogenic peptides and proteins as a vaccine delivery system 14:10 – 14:30 Runa Begum Fabricating an extracellular matrix analogue using natural polymers for cartilage tissue engineering applications 14:30 – 14:50 Wenjin Xiao Using bacterial adhesins to direct human stem cells to the myocardium 14:50 – 15:20 Coffee and posters East foyer Session 3: Systems Chair: Dr Adam Perriman 15:20 – 15:40 Liangfei Tian Out of equilibrium protocell systems 15:40 – 16:00 Natalie di Bartolo Molecular membrane engineering for nanoreactors 16:00 – 17:00 Professor Katharina Closing plenary Landfester, Max Nanocapsules as cell modules Planck Institute for Polymer Research 17:00 – 18:00 Drinks, poster prizes and networking Public Lecture Chair: Professor Imre Berger, Director, BrisSynBio 18:00 – 19:00 Professor Nadrian DNA. Not merely the secret of life Seeman, University of New York 3 PLENARY SPEAKERS Dr Paul Race School of Biochemistry, University of Bristol Kill or cure: Repurposing bacterial adhesins for therapeutic payload delivery Abstract: Adherence of bacteria to biotic or abiotic surfaces is a prerequisite for host colonisation and represents an important step in microbial pathogenicity. This attachment is facilitated by bacterial adhesins at the cell surface. Due to their size and often elaborate multi-domain architectures, these polypeptides represent challenging targets for detailed structural and functional characterisation. Here I outline how fundamental studies of the multifunctional fibrillar adhesin CshA have revealed a hitherto unreported mechanism of human cell surface binding, which is now being exploited as the basis for a stem cell homing technology. Biography: Paul is a senior lecturer in Biochemistry at the University of Bristol. He leads the pan-UK EPSRC funded Manufacturing Immortally project, which aims to develop bio-hybrid self-healing ‘living materials’. He is a former Co- Director of the BrisSynBio synthetic biology research centre, and was a founding Director of the Bristol BioDesign Institute. He is co-founder and non-executive Director of the University of Bristol spinout company Zentraxa Ltd., which uses a proprietary biodesign platform to develop bioadhesives for aerospace, marine and medical applications. 4 PLENARY SPEAKERS Professor Katharina Landfester Max Planck Institute for Polymer Research, Mainz, Germany Nanocapsules as cell modules Abstract: Since many years, there is a quest for minimal cells in the field of synthetic biology, potentially allowing a maximum of efficien¬cy in biotechnological processes. Although the so-called “protocells” are usually referred to in all papers that attempt a cumulative definition of Synthetic Biology, research in this area has been largely underrepresented. Our aim is at developing vesicular structures, i.e. protocells, based on block copolymer self-assembly and engulfed nanocontainers with incorporated functions, such as energy production and the control of transport properties through nanomembranes. Therefore, we have designed and developed nanocapsules that act as cell-like compartments and can be loaded with enzymes for synthetic biology and chemistry. In addition, self- assembly of well-defined diblock copolymers has been used to generate polymersomes and hybrid liposomes/polymersomes. Both strategies allow the compartimentalization on the nano- or microscale and conducting enzymatic or chemical reactions in the confinement of the polymersomes/ nanocarriers. New block copolymers and permeable nanocarriers have been synthesized and optimized. With these protocols we were able to establish an enzymatic reaction cascade within droplet-based compartments. These compartments can act as cell-like functions to regenerate NAD. For these tasks, novel conductive polymer nanoparticles have been developed which will be included into the protocells for the NAD regeneration by light. Also enzyme-complexes are assembled that will fulfill these requirements. Transmembrane transport of ions, molecules and particles is also fundamental to functionality in biology. However, the direct investigation in living cells is very difficult due to the complexity of biological membranes and the diverse coupling of interactions. Therefore, transport of nanoparticles into a minimal model system, based also on a vesicle-forming amphiphilic copolymer was probed in our group. The physical properties of these copolymer molecules are similar to phospholipids and therefore provide the necessary fluidity of a membrane, while ensuring excellent mechanical stability at the same time. The latter is due to the slow exchange
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