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Biography |
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Name: Martha Rebecca Jane Clokie Date of Birth: 14 June 1973 Nationality: British Position: Professor. Positions Held April 2011 – April 2015(Associate Professor) in Microbiology at the University of Leicester September 2006 – March 2011 New Blood Lecturer at the University of Leicester June – August 2006 Visiting Scholar at Scripps Institution of Oceanography, San Diego, USA January 2004 – May 2006 Post-doctoral Researcher at the University of Warwick. Title: Virus-mediated photosynthesis in the oceanic cyanobacterial picoplankton January 2001 – December 2003 post-doctoral Researcher at the University of Warwick. Title: Bacteriophage biodiversity and horizontal gene transfer in the marine environment Academic Education 1997 – 2000 University of Leicester, PhD Molecular Ecology 1996 – 1997 University of Edinburgh, MSc Plant biodiversity and taxonomy 1992 – 1996 University of Dundee BSc (Hons) Biology 1st class Research Interests: The ecology and molecular biology of bacteriophages and their relationships with bacterial hosts. The exploitation of phages for improved therapeutics and diagnostics. Determining the molecular basis of successful interactions between phages and their hosts. National and international science advisory and policy: Organizing committee for SGM Session on Bacteriophages in the Environment (September 2013), Organizing committee for Environmental Phage Workshop Arizona (January 2013), Organizing committee for Viruses of Microbes Society (Last meeting in Brussels 2012), Organizing committee for Evergreen International Phage meetings (2013, 2011, 2007), Joint chair of the UK, Viral Ecology Group, Member of bacteriophage classification study group for the International Committee on Taxonomy of Viruses, Executive member of the British Phycological Society (2006-2010), Member of the advisory council of the PhageBiotics Foundation (USA). Editorial work: Member of the editorial Board for journal ‘Bacteriophages’ launched in January 2010 and for PloSONE. Edited and wrote chapters in Bacteriophages: Methods and Protocols. Published by Springer in 2009. Regularly review manuscripts for Nature Reviews Microbiology, Environmental Microbiology, Journal of Applied Microbiology, Letters in Applied Microbiology, Journal of Phycology, Journal of Medical Microbiology, Virology Journal, Applied and Environmental Microbiology, FEMS Microbial Lett., Proteomics. Regular grant reviewer for MRC, BBSRC, NERC, Welcome Trust, NSF. Invited presentations at international meetings (selection): Aquatic Viral Workshop, St Petersburg USA, November 2013; 1st International Phage Biotechnology course, Braga, Portugal. July 2013. EU/NSF Microbial Community dynamics, St Louis, USA November 2012; Europhages; Oxford, September 2012; Viruses of Microbes. Brussels. June 2012; Euroscicon meeting on The Bacteriophage in Biology, Biotechnology and Medicine, London, UK. January 2012; SGM, Horizontal Gene Transfer, University of York. September 2011; 19th Evergreen International Phage Meeting, Olympia, USA. August 2011; SGM Irish Division. Queens University, Belfast. April 2011; Viruses of Microbes. Pasteur Institute, Paris; February 2011. Research colloquia and seminars (selection): London School of Medicine and Tropical Hygiene (2013). University of Liverpool (2013). University of Nottingham (2012), University of Warwick (2012), University of Mahidol Bangkok (2012), Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam (2012), University of Bergen, March 2010, National Institutes of Health, Bethesda USA. January 2009, National Institutes of Health, Bethesda, USA. August 2007, Stanford University, USA. August 2006, San Diego State University, USA.
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Abstract |
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New strategies to get ready for a post antibiotic era: a treasure trove of options from bacteriophages |
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Throughout the world, bacteria are becoming increasingly resistant to antibiotics. This is due to their overuse both directly in humans, and within the food chain. Antibiotic-resistance has the worrying consequence that humans could be plunged into a pre-antibiotic era where patients die from an infection that can’t be treated. Bacteriophages are naturally occurring viruses that target and kill bacteria, generally with very specific interactions. They were isolated over 100 years ago and have been used all over the world to treat a range of bacterial infections. In most places however, research on their development and exploitation was curtailed following the discovery of antibiotics, as they were deemed unnecessary and too complicated. The emergence of antibiotic resistance has promoted a resurgence of interest in the use of bacteriophages as therapeutics. They could potentially be used as a treatment or prophylactic option for many bacterial infections.
In light of the growing antibiotic crisis, the Wellcome Trust and UK Department of Health commissioned a panel of 24 scientists and physicians to identify alternatives to antibiotic therapy. They considered ten approaches worthy of development, three of which were phage based; wild-type phages, engineered phages and lysins (Czaplewski et al., The Lancet, 2015). In this talk I will discuss the merits, challenges and limitations of these three approaches. It is likely that there will not be a ‘one phage-approach’ suits all solution, and that these different options will be effective for particular infection profiles.
Clearly it is an exciting time to be studying phages and they can teach us a lot about how to selectively kill bacterial pathogens. They encode the largest amount of genetic diversity on earth, and little detailed characterisation has been carried out for most phage groups. An example of the benefits of understanding the exquisite specificity between bacteria and their phages can be seen from CRISPR-Cas genes that are part of the bacterial immunity to detect and degrade specific invading DNA. This knowledge has spawned a whole industry, and been adapted for genome editing of many species, including human. There are a lot of phage products encoded within phage genomes that are currently annotated as encoding ‘hypothetical’ proteins, but which could indeed be ‘hypothetical antimicrobials’. Significant fundamental research investment is required to understand and exploit this valuable resource.
I will give an overview of phage therapy past, present and future. I will give examples from my own lab and from the work of others on how phages can be developed to target specific bacterial groups. I will focus on examples using phages to target Clostridium difficile, Salmonella spp., Pseudomonas aeruginosa and Borrelia. I will show how the initial phage discovery, characterisation including sequencing, is essential but not without challenge. I will then present data on how different ex situ models can reveal how phages are most likely to be effective in infection settings.
In summary, given appropriate research investment, phages have huge potential to be developed as specific antimicrobials for a range of pathogens. The use of phages to treat human infection can be viewed as a part of a personalised medicine approach where instead of obliterating our helpful commensal bacteria; they will maintain it whilst removing the pathogens that cause disease.
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