2014 - Exploiting bacteriophages for bioscience, biotechnology and medicine (the 5th in a biennial series)

London
Thursday, 23 January 2014

This is a Euroscicon Small Conference,  an outline of the day can be found at 
www.euroscicon.com/EurosciconMeetingStructure.pdf

2014 - Exploiting bacteriophages for bioscience, biotechnology and medicine (the 5th in a biennial series)
Thursday, 23 January 2014 09:00 - 17:00

Cineworld: The O2
Peninsula Square
London
SE10 0DX
United Kingdom


Bacteriophages (phages) are arguably the most abundant biological entities on the planet. They play crucial roles in driving the adaptive evolution of their bacterial hosts, and achieve this both through the predator-prey roles of the phage-bacterium interaction and through the adaptive impacts of lysogeny and lysogenic conversion.  Bacteriophages are the source of many biochemical reagents and technologies, indispensible for modern molecular biology.  Furthermore, phages are being exploited in other areas of biotechnology, including diagnostics, prophylaxis and other aspects of food microbiology. In recent years there has been a growing interest in developing phages for therapeutic purposes (phage therapy) as natural alternatives to antibiotics. The inexorable rise in the incidence of antibiotic resistance in bacterial pathogens, coupled with the disappointingly low rate of emergence of new, clinically useful antibiotics, has refocused attention on the potential utility of phages for treating human and animal disease. Examples of the roles of phages in fundamental biological research and in medical and industrial biotechnologies will be discussed at this meeting. On registration you will be able to submit your questions to the panel that will be asked by the chair on the day of the event. This event has CPD accreditation.

Meeting chair: Professor George Salmond, University of Cambridge, UK

9:00 – 9:40         Registration

9:40 – 9:45         Introduction by the Chair: Professor George Salmond, University of Cambridge, UK

9:45 – 10:10       Bench to bedside with phage-derived antibodies
Professor Kerry Chester,
UCL Cancer Institute, UK

10:10 – 10:35     Ecological Aspects of Bacteriophage in the Wider Environment
Dr Brian Reavy,  The James Hutton Institute, Scotland UK
High throughput sequencing technologies and metagenomic approaches are revolutionising our understanding of the composition of bacteriophage populations and their potential  roles in the wider environment. Much of this work has concentrated on viruses in marine environments and only recently have studies been extended to examine in detail the viruses present in soils.Recent advances will be discussed with an emphasis on how this is framing our view of the roles of bacteriophages as reservoirs of metabollicaly important host genes specific to distinct environments, and how they potentially reflect and affect microbial ecosystem functioning.


10:35 – 11:00      Speakers’ photo then mid-morning break and poster exhibition and trade show

11:00 – 11:25       Purification of bacteriophages using methacrylate based monolithic columns
Dr. Lidija Urbas
, Head of Marketing, BIA Separations, Slovenia
Methacrylate based monolithic columns were developed for efficient isolation and purification of large biomolecules like
proteins (IgG, IgM), virus-like-particles, viruses and DNA. Monolithic columns consist of a stationary phase that is a solid single piece continuous bed with internal porosity of 60% and a specially designed housing. The mobile phase and sample to be separated are driven by a pressure force through large, highly interconnected and easily accessible channels that are covered with appropriate ligands. This results in a convective flow enhanced mass transfer which enables highly efficient and flow independent chromatographic separation. The purification of the target molecule can therefore be achieved in a much shorter time in comparison to traditional particle based chromatographic media, without compromising the efficiency of the purification process. In this lecture we will present how to develop purification processes for various bacteriophages based on their properties and characteristics. A basic approach on how to start phage purification on a small scale and then transfer it to large scale will be shown. Additionally the ability of monolithic columns to monitor phage content during different phage production steps (in-process control) in nearly real time will be presented. The “snap shot” can help process developers determine the appropriate time for product extraction, but it also serves as an integration tool between upstream and downstream aspects of the process.

11:25  – 12:55     Oral Presentations:
11:25  – 11:40    
ISOLATION OF A BACTERIOPHAGE COCKTAIL EFFECTIVE ON THE ERADICATION OF STAPHYLOCOCCUS AUREUS BIOFILMS
D. R. Alves
, M. C. Enright, A.T.A. Jenkins
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK


11:40  – 11:55    REGULATION OF BACTERIAL TRANSCRIPTION BY NON-BACTERIAL TRANSCRIPTION FACTORS
Wigneshweraraj, S

MRC Centre for Molecular Bacteriology and Infection, Flowers Building, Imperial College London, London SW7 2AZ


11:55  – 12:10    USE OF BACTERIOPHAGE TO DETECT VIABLE MYCOBACTERIA IN BLOOD WITHIN 48 H
B. Swift
, E. Denton, S. Mahendren, J. Huxley, C. Rees
School of Biosciences, Sutton Bonington Campus, University of Nottingham, Nr Loughborough, Leics, LE12 5RD


12:10  – 12:25    ENHANCEMENT OF THE ANTIMICROBIAL PROPERTIES OF BACTERIOPHAGE K VIA STABILISATION IN OIL-IN-WATER NANO-EMULSIONS
Patricia Perez Esteban1, 2*, A.T.A. Jenkins1, Thomas Arnot2
1
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK, 2Department of Chemical Engineering, University of Bath, Claverton Down, Bath, BA2 7AY, UK

12:25  – 12:40    
GENOMIC AND BIOLOGICAL ANALYSES OF BACTERIOPHAGES: A MODEL FOR PSEUDOMONAS SYRINGAE PHAGE-THERAPY
D Frezza,
P D’Addabbo, R Braglia, M Evangelisti, M Scortichini , M C Thaller, G Di Lallo, Department of Biology, University of Tor Vergata, viale della ricerca scientifica, Roma Italy

12:40  – 12:55    THE PERFECT VIRUS: NOVEL SALMONELLA PHAGE S16 FEATURES A BROAD HOST RANGE AND TAIL FIBER TOOLS FOR RAPID AND SPECIFIC DETECTION OF ITS TARGET CELLS
Martin J. Loessner

Institute of Food, Nutrition and Health, ETH Zurich, 8092 Zurich, Switzerland

12:55  – 13:45      Lunch, poster exhibition and trade show

13:45 – 14:15       Discussion session
This discussion session is an informal question and answer session.  This is an ideal opportunity to get advice and opinion from experts in this area. This session is not for questions about specific talks, which can be asked after the speakers session, but for discussing either general topics or specific issues.
There are three ways you can ask questions:
1.    Before the session you can
submit your question to Euroscicon staff at the registration desk, 2.    Before and during the session you can submit a question or comments, by email, which will be provided on the day of the event
3.    During the session you can
put your hand up and join in

14:15 – 14:40      
Mining the microbiota for novel phage therapies
Professor Colin Hill, Professor of Microbial Food Safety,  University College Cork, Ireland
The gastrointestinal tract is probably the most densely populated ecosystem in nature, containing as many as 10>15 bacteriophage particles.  We are interested in 'mining' this ecosysytem for effective antimicrobials, including bacteriophages.  In this talk I will present an example of the isolation of phages against Pseudomonas aeruginosa in the lungs of cystic fibrosis patients, which has been validated in cell lines and in murine models.

14:40 – 15:05      Phage nanobiotechnology: from phage display technology to targeted gene delivery
Dr Amin Hajitou, Imperial College Faculty of Medicine, UK
Phage nanobiotechnology has expanded its applications in diverse disciplines. Yet bacteriophages are still considered poor vectors for gene transfer applications as they have no optimised strategies to deliver genes to mammalian cells. We have investigated the barriers to phage-guided gene transfer and found that one of the limitations is phage surface negative charge hindering accessibility to negatively charged eukaryotic cell membranes. Next, we established that the major intracellular obstacle is phage sequestration in endosomes and degradation in lysosomes. To overcome these limitations, we generated a multifunctional bacteriophage with a positive charge and that allows display of strategies to improve gene transfer.


15:05 – 15:30        Afternoon Tea,  last poster session and trade show    

15:30 – 15:55       
Blocking Cell Signalling with Recombinant Antibodies
Dr John McCafferty,
University of Cambridge, UK 
Recombinant antibodies provide a means to control receptor activation with utility in the treatment of cancer. Using phage display in conjunction with a traditional cell based screening assays we have generated and affinity matured human antibodies to a number of developmentally important, cancer-related targets including the receptor tyrosine kinase c-Met, Notch1/Notch 2 and the metalloprotease ADAM17. These functional human antibodies affect cell signaling by a number of different modalities including ligand neutralisation, receptor blocking, signal processing and stabilisation of inactive conformations.

15:55 – 16:20       Phages can be the problem and targeting them might be the solution
Professor David Gally, Division of Infection and Immunity, The Roslin Institute, University of Edinburgh, UK
For a number of bacterial pathogens key virulence factors are encoded on lysogenic bacteriophages. This is certainly the case for enterohaemorrhagic
E. coli (EHEC) strains for which the serious pathology in humans is associated with phage-encoded Shiga toxins (Stx).  Our collaborative research has demonstrated that specific Stx-encoding phages are also associated with higher EHEC excretion levels from cattle, the main reservoir host, increasing the risk of human infection.  Moreover, recent research indicates that phage-encoded Stx can potentially be expressed in eukaryotic cells and therefore targeting phage production and phage trafficking during animal or human infection may offer novel therapeutic options to prevent EHEC and other ‘bacterial’ diseases.    

16:20 - 16:45        Temperate phages infecting Pseudomonas aeruginosa in chronic lung infections
Dr Darren Smith, Senior Lecturer in Biology, Northumbria University, UK
Pseudomonas aeruginosa is associated with lowered lung function in genetic disorders such as Cystic Fibrosis (CF), non-CF Bronchiectasis and COPD. There are pathophysiological similarities between these conditions where we will present the differences in phage communities/biology even though bacterial communities present are deemed to be almost identical.

16:45 - 17:00        Chairman’s Summing Up and Close of Meeting


Key Words: Abortive, Infection, Bacteriophage, Resistance,Toxin ,Purification Monolith,Yield ,Scaleable, cGMP, clinical trials, regulation, FDA, EMA, therapeutic use, lung, infection, Campylobacter, phage therapy, poultry, biofilms, Clostridium difficile, bacteriophages, genomes, diagnostic, therapeutic, Metagenomics, ecology, microbial functioning, bacteriophages,Genomics, Metabolism, Clostridium difficile, Pseudomonas aeruginosa, gastrointestine, Bacteriophage, gene delivery, targeted gene therapy, phage nanobiotechnology.

Meeting reports from this event will be published by  HONNAO publishing,  Expert Reviews in Anti-infective Therapy and Pharmaphorum.


About the Chair
George Salmond
is currently in the Department of Biochemistry at the university of Cambridge. He graduated in microbiology (BSc, Strathclyde) followed by a PhD in bacterial genetics and phage)host interactions (Warwick) and an MA and ScD (Cambridge). He has taught in Kent, Warwick and Cambridge universities. He has multiple research interests in microbiology, including the molecular basis of bacterial virulence in plant and animal pathogens, quorum sensing, biosynthesis and regulation of bioactive secondary metabolites (including antibiotics), protein secretion systems, and the biology and exploitation of bacteriophages ) the subject of this meeting. He has long standing interests in the isolation of novel phages from the natural environment for the development of genetics and functional genomics of diverse bacteria, including plant, animal and human pathogens. He also has current research interests in how bacteria evade the potentially lethal impacts of viral infection via phage abortive infection systems.  

About the Speakers
Kerry Chester
leads the Recombinant Antibody Therapeutics Group at the UCL Cancer Institute (http://www.ucl.ac.uk/cancer/). Her main research interests are design and construction of antibody-based therapeutics and the interaction of these molecules with specific cancer targets. The work is largely translational and aimed at developing new agents for clinical use. Current research includes developing antibodies as cancer imaging agents, as antibody drug conjugates and to target novel nanomedicines. Antibody phage-display is a platform technology for creating these novel antibody-based therapeutics.

Brian Reavy is a molecular biologist with an extensive background in virology. After his doctoral studies on viruses of insects at Oxford he worked on foot-and-mouth disease virus genetics at the Animal Virus Research Institute (now Pirbright laboratory). Following a spell in the pharmaceutical industry he moved to the Scottish Crop Research Institute (now incorporated into The James Hutton Institute) where he has studied plant viruses with an emphasis on vectored transmission mechanisms. In the last few years he has started to apply modern molecular techniques to examine ecological aspects of viruses, particularly bacteriophage in soils.

Lidija Urbas studied chemistry at the University of Ljubljana, Faculty of Chemistry and Chemical Technology where she graduated in 2005. She than joined the company BIA Separations, where she was working as a research scientist for 6 years. Her main task and a part of her PhD study was the development of downstream processes for the purification of viruses and virus like particles and the development of analytical monolithic column and methods for PAT. After her PhD she became a Project Manager, leading projects dealing with purification and analytics of biomolecules and in 2013 she became Head of Marketing.

Colin Hill has a Ph.D in molecular microbiology and is Professor of Microbial Food Safety in the Microbiology Department of University College Cork, Ireland. His main interests are in infectious disease, particularly in defining the mechanisms of virulence of foodborne pathogens and in developing strategies to prevent and limit the consequences of microbial infections in the gastrointestinal tract. He has published more than 375 peer-reviewed papers and has served on the Scientific Committee of the Food Safety Authority of Ireland for many years. In 2005 Prof. Hill was awarded a D.Sc by the National University of Ireland in recognition of his contributions to research. In 2009 he was elected to the Royal Irish Academy and in 2010 he received the Metchnikoff Prize in Microbiology.

Amin Hajitou obtained his BSc from the University of Fes, Morocco, then Master and PhD from the University of Liège, Belgium. His PhD involved use of retroviral vectors for oncogene transfer. Next, he enhanced his skills in vector technologies using viral vectors to systemically deliver inhibitors of tumour angiogenesis invivo. In 2002, Dr Hajitou joined the MD-Anderson Cancer Center of the University of Texas. There, he acquired substantial expertise in phage technologies and designed new generation of hybrid phage nanoparticles for targeted systemic gene delivery. Since 2007, Dr Hajitou established his group, as a Lecturer, at Imperial College London and became Senior Lecturer in 2013.

In 1990 John McCafferty was one of the founders of CAT (now Medimmune) and was the principal inventor of antibody-phage display. After 12 years at CAT John established labs at the Sanger Institute and then at the Biochemistry Dept at University of Cambridge utilizing phage display technology to develop functionally blocking antibodies with potential in cancer and stem cell biology. In 2012 John has established IONTAS, a small innovative biotechnology company using phage display to develop novel antibody therapeutics.

Darren Smith's postgraduate research has spanned 12.5 yr and has targeted the biology of temperate bacterial viruses and the nano therapy of HIV. Currently he is a Senior Lecturer leading a new but active research group studying the dynamic interplay between Pseudomonas aeruginosa phages and their bacterial host, elucidating their involvement and influence on chronic lung disease. He is the PI of a sequencing facility focusing on viral genomics and host subversion.

 

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