Micro Biology

40:1 Feb 2013

Micro biology

TodayQuarterly Magazine of the Society for General Microbiology

Viruses and cancer • HIV and immune suppression • Human papillomaviruses • Viral hepatitis and HCC • Vaccines for Epstein–BarrMicrobiology virus Today Feb 2013 1 22337_Chloramphenicol Ad_Micro Today_AW:1 11/4/12 17:10 Page 1 CHLORAMPHENICOL

Widely distributed throughout the body, including CSF1 Editorial Oral levels comparable to i.v. levels2

3 Rarely implicated with C.difficile

Effective against serious infections including: H. influenzae1,2 Typhoid1,2 Welcome to the first issue of MRSA4 Microbiology Today of 2013, which will VRSA5 Neisseria1,2 be a year of great change for SGM. Legionella1,2 I will be finishing my tenure as Editor human papillomaviruses by Jo Parish 1,2 Rickettsia of Microbiology Today in September. & Sally Roberts. Robert Newton also 6-9 C.difficile The excellent Laura Bowater, a senior provides us with an excellent overview E. coli1 lecturer in the Medical School from the of the epidemiological burden of virus- University of East Anglia will succeed me associated cancers. in the post. I hope Laura will find the We have also included an post as enjoyable, stimulating and interview with Professor zur Hausen, Abbreviated Prescribing Information respiration and death within a few hours of the onset of symptoms. fun as I have – good luck! where he gives us a great insight into Chloramphenicol Capsules BP 250mg Overdose: Stop chloramphenicol immediately if signs of adverse events develop. Treatment is mainly supportive. If an allergy develops, This issue of Microbiology Today his work and career in virology. In all, it Presentation: Capsules containing 250mg chloramphenicol BP. oral antihistamines may be used. In severe overdosage e.g. Gray Baby Indications: Typhoid fever and life-threatening infections, particularly Syndrome, reduce plasma levels of chloramphenicol rapidly. Resin is a ‘virology special’; this is in part really is a tour de force of the area. those caused by Haemophilus Influenzae, where other antibiotics will haemoperfusion (XAD-4) has been reported to substantially increase not suffice. chloramphenicol clearance. to recognise the contribution of this The Comment in this issue is Posology: For oral administration. Pack size and Price: 60 capsules £377.00 year’s SGM Prize Medal winner, Harald provided by Leighton Chipperfield, Adults and elderly: 50mg/kg body weight daily in 4 divided doses. Legal Category: POM. For severe infections (meningitis, septicaemia), this dose may be Market Authorisation Number: PL17736/0075. zur Hausen, and his ground-breaking Head of Publications at SGM, where doubled initially, but must be reduced as soon as clinically possible. Market Authorisation Holder: Chemidex Pharma Limited, 7 Egham Children: Not recommended. Business Village, Crabtree Road, Egham, Surrey TW20 8RB, UK. contributions to understanding the link he outlines the challenges and Contra-indications: Known hypersensitivity or toxic reaction to Date of preparation: April 2012. chloramphenicol or to any of the excipients. Should not be used See Chloramphenicol Summary of Product Characteristics for full between viruses and cancer. The issue opportunities that lay ahead for SGM in for the prophylaxis or treatment of minor infections; during active prescribing information. immunisation; in porphyria patients; in patients taking drugs liable owes a huge debt to David Blackbourn, the changing landscape that is academic to depress bone marrow function; during pregnancy, labour or by breast-feeding mothers. Adverse events should be reported. Reporting forms and whose knowledge and expertise in this publishing. Special warnings and precautions for use: Use only if other treatments information can be found at www.mhra.gov.uk/yellowcard. area was invaluable in identifying and I hope you enjoy this issue of are ineffective. Use should be carefully monitored. Reduce dose and Adverse events should also be reported to Essential monitor plasma levels in hepatic or renal impairment in the elderly and Microbiology Today. in patients concurrently treated with interacting drugs. Generics on 01784 477167. inviting authors – in fact David did most Interactions: Chloramphenicol prolongs the elimination, increasing the of the author identification and arm- blood levels of drugs including warfarin, phenytoin, sulphonylureas, tolbutamide. Doses of anticonvulsants and anticoagulants may need to References twisting! We have relied heavily on the PAUL A. HOSKISSON, Editor be adjusted if given concurrently. Complex effects (increased/decreased 1. Sweetman S.C. (ed), Martindale: The Complete Drug Reference. plasma levels) requiring monitoring of chloramphenicol plasma levels [online] London: Pharmaceutical Press Viral Oncology group at the University Email [email protected] have been reported with co-administration of penicillins and rifampicin. (Accessed on 22 August 2011).

Paracetamol prolongs chloramphenicol half-life. Chloramphenicol may 2. Feder, H. Chloramphenicol: What we have learned in the last Decade. 22337 of Birmingham, who have done a great increase the plasma levels of calcineurin inhibitors e.g. ciclosporin Southern Medical Journal. 1986; 79(9): 1129-34. 3. Kelly, C., LaMont, T. and tacrolimus. Barbiturates such as phenobarbitone increase Patient information: Antibiotic-associated diarrhea (Clostridium difficile). job. It has been a fascinating issue to the metabolism of chloramphenicol, resulting in reduced plasma www.uptodate.com. (Accessed on 11 August 2011). 4. Fluit, A.C., chloramphenicol concentrations. In addition, there may be a decrease Wielders, C.L.C., Verhoef, J., and Schmitz, F.J. Epidemiology and edit and I have learned a huge amount in the metabolism of phenobarbitone with concomitant chloramphenicol Susceptibility of 3,051 Staphylococcus aureus Isolates from 25 in this area. use. There is a small risk that chloramphenicol may reduce the University Hospitals Participating in the European SENTRY Study. contraceptive effect of oestrogens. Chloramphenicol reduces the Journal of Clinical Microbiology. 2001; 39(10): 3727-3732. 5. Weigel LM We begin with an overview of response to hydroxocobalamin. Chloramphenicol is contra-indicated et al. High-Level Vancomycin-Resistant Staphylococcus aureus (VRSA) in patients taking drugs liable to suppress bone marrow function Associated with a Polymicrobial Biofilm. Antimicrobial Agents and viruses and cancer by Laura Hindle & e.g. carbamazepine, sulphonamides, phenylbutazone, penicillamine, Chemotherapy. Published online ahead of print on 30 October 2006. cytotoxic agents, some antipsychotics including clozapine and http://aac.asm.org/cgi/reprint/AAC.00576-06v1.pdf. (Accessed on David Blackbourn, followed by several particularly depot antipsychotics, procainamide, nucleoside reverse 22 August 2011). 6. Ensminger, P., Counter, F., Thomas, L., Lebbehuse, transcriptase inhibitors, propylthiouracil. P. Susceptibility, Resistance Development, and Synergy of Antimicrobial articles covering more specific areas of Pregnancy and Lactation: The use of chloramphenicol is contra-indicated Combinations Against Clostridium difficile. Current Microbiology. Essential Generics: Chloramphenical Ad as the drug crosses the placenta and is excreted in breast milk. 1982; 7: 59-62. 7. Poilane, I., Bert, F., Cruaud, P., Nicolas-Chanoine, interest. These cover a range of viruses Effects on ability to drive and use machines: No significant effect MH., Collignon, A. Interest of the disk diffusion method for screening on driving ability. Clostridium difficile isolates with decreased susceptibility to antibiotics. and diseases such as viral hepatitis and Undesirable Effects: Reversible dose related bone marrow depression, PathologieBiologie (Paris). 2007; 55(8-9): 429-33. 8. Cattoir, V., hepatocarcinoma by Jane McKeating irreversible aplastic anaemia, increased bleeding time, hypersensitivity Ould-Hocine, ZF.,Legrand, P. Antimicrobial susceptibility of Clostridium reactions including allergic skin reactions, optic neuritis leading to difficile clinical isolates collected from 2001 to 2007 in a French CAPSULES & Colin Howard, Epstein–Barr virus blindness, ototoxicity, acidotic cardiovascular collapse, nausea, vomiting, university hospital. PathologieBiologie (Paris). 2008; 56(7-8): 407-11.

glossitis, stomatitis, diarrhoea, enterocolitis, Gray Baby Syndrome 9. Brazier, JS., Levett, PN., Stannard, AJ., Phillips, KD., Willis, AT. mm Bleed: 3 mm Supply as hi-res PDF Job no: by James Turner & Graham Taylor and particularly in the newborn, which consists of abdominal distension, Antibiotic susceptibility of clinical isolates of clostridia. Journal of PIP: 106-5796 210

EG/CH/APR/2012/08 pallid cyanosis, vomiting, progressing to vasomotor collapse, irregular Antimicrobial Chemotherapy. 1985; 15(2): 181-5. x

AAH: CHL600B 297 ALLIANCE: O65995 2 Microbiology Today Feb 2013 Microbiology Today Feb 2013 1 Trim size: Trim Journal: Microbiology Today Journal: Microbiology Today MOVIANTO: CHL25060 For further information, please contact: Essential Generics, 7 Egham Business Village, Crabtree Road, Egham, Surrey TW20 8RB, UK Contents SGM Council 12/13 MICROBIOLOGY TODAY 40:1 Feb 2013 features www.sgm.ac.uk/pubs/micro_today

38 Schoolzone 44 How to Executive Officers James Redfern organise a President – Professor Nigel L. Brown describes a virus conference c/o Society for General Microbiology, Marlborough House, practical that can Karen McGregor articles Basingstoke Road, Spencers Wood, Reading RG7 1AG be carried out in presents advice Tel. 0118 988 1801; Email [email protected] schools. for early-career 16 Introducing General Secretary – Professor David J. Blackbourn University of Birmingham, Cancer Research UK Institute for Cancer researchers. viruses and cancer Good bugs, Studies, Edgbaston, Birmingham B15 2TT 40 Laura N. Hindle & Tel. 0121 415 8804; Email [email protected] bad bugs Interview 48 David J. BlackbourN Treasurer – Professor Colin R. Harwood Jo Verran & Nobel Prize and An overview of cancer and tumour virology Centre for Bacterial Cell Biology, Institute for Cell and Molecular Paul Hoskisson SGM Prize Biosciences, Baddiley Building, University of Newcastle, Newcastle upon to complement the accompanying articles in relate their Medal Winner Tyne NE2 4AX this issue. Tel. 0191 208 3221; Email [email protected] experience of Professor Harald Chairs of Committees working on a zur Hausen reflects 22 Cancers Communications Committee – Professor Joanna Verran microbiology series on his career in attributable Department of Biology, Chemistry and Health Science, Manchester for Fun Kids virology. to infection – the Metropolitan University, Chester Street, Manchester M1 5GD radio. Tel. 0161 247 1206; Email [email protected] 52 Comment global burden Finance Committee – Professor Colin R. Harwood (see ‘Treasurer’ above) Robert Newton 42 Standing up Head of Cover Coloured transmission Professional Development Committee – Dr Sara Burton Infections are the most important cause for Science Publishing at electron micrograph of human Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter of cancer after tobacco. What are the EX4 4QD Erica Kintz reports SGM, Leighton immunodeficiency virus, one of the Tel. 01392 263437; Email [email protected] on a workshop Chipperfield, prospects for prevention of infection- seven viruses defined as carcinogens by Policy Committee – Professor Nigel L. Brown (see ‘President’ above) for early-career discusses the associated cancers? the International Agency for Research on Cancer. James Cavallini / Science Photo Library Publications Committee – Professor Charles Penn researchers held challenges School of Biosciences, University of Birmingham, Edgbaston, at the University facing scientific Editor Birmingham B15 2TT Dr Paul A. Hoskisson Tel. 0121 414 6562; Email [email protected] of Glasgow in publishing. Scientific Conferences Committee – Dr Evelyn M. Doyle November 2012. Managing Editor and Design School of Biology & Environmental Science, University College, Ian Atherton Ardmore House, Dublin 4, Republic of Ireland Editorial Assistant Tel. +353 1 716 1300; Email [email protected] Yvonne Taylor Elected Members 26 Human 30 Viral hepatitis Address Professor Andrew Davison MRC-University of Glasgow Centre for reguLars papillomaviruses and hepatocellular SGM, Marlborough House, Basingstoke Virus Research, Church Street, Glasgow G11 5JR Road, Spencers Wood, Reading RG7 1AG Tel. 0141 330 6263; Email [email protected] Jo parish & sally roberts carcinoma Tel. 0118 988 1842 Email [email protected] Professor Ian R. Henderson Division of Immunity & Infection, What mechanism do these wart-causing Jane A. McKeating & © 2013 Society for General Microbiology University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT 1 Editorial viruses use to induce cancer and what can we Colin R. Howard ISSN 1464-0570 Tel. 0121 414 4368; Email [email protected] do about it? It is vital that we increase our understanding Printed by Latimer Trend & Co. Ltd, Dr Paul A. Hoskisson Strathclyde Institute of Pharmacy & Biomedical 5 From the President Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE of the mechanisms underlying virus-induced Plymouth Tel. 0141 548 2819; Email [email protected] 6 News 34 Epstein–Barr liver cancer to provide new targets for Dr Karen Robinson Centre for Biomolecular Sciences, University of virus: opportunities therapeutic intervention and vaccination. Nottingham, University Park, Nottingham NG7 2RD 12 Conferences Tel. 0115 823 1094; Email [email protected] for prophylactic and Professor John H. Sinclair Department of Medicine, Level 5, Laboratory 14 Microshorts therapeutic vaccines The views expressed by contributors do not Block, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ James E. Turner and necessarily reflect official policy of the Society; Tel. 01223 336850; Email [email protected] 43 SGM Journals Graham S. Taylor nor can the claims of advertisers be guaranteed. Professor Maggie Smith Department of Biology, University of York, society for general Wentworth Way, York YO10 5DD 50 Reviews Are vaccines the answer to fight this Tel. 01904 328500; Email [email protected] ubiquitous cancer-causing virus? Microbiology

2 Microbiology Today Feb 2013 Microbiology Today Feb 2013 3 from the The 7th International Yakult Symposium The Intestinal Microbiota and Probiotics: president Exploiting Their Infl uence on Health www.yakultsymposium.com

2013 is a year that will bring great change Department of Health on steps being taken to minimise further resistance and to the Society. For the last 2 years, Council asked the Business, Innovation and Skills Department about investment in new and senior Marlborough House staff have antimicrobials. With the help of members, the been working hard to meet the challenges SGM can respond rapidly to issues of microbiological concern. The recent that the SGM will face. concerns over ash dieback led to us We are restructuring our publications that our current location reduces quickly producing a briefing note activity and Leighton Chipperfield, the our opportunities to engage with (www.sgm.ac.uk/news/hot_topics/ Head of Publishing, describes some of opinion-formers and with other Ashdiebackbriefing.pdf) with the the changes in publishing in this issue learned societies. Council has agreed help of Dr Robin Sen of Manchester April 22nd-23rd, 2013 (p. 52). Open Access (OA) publishing to move over the course of 2013 Metropolitan University. Such briefing has been widely discussed following to Charles Darwin House (www. notes are valued by politicians, civil The Queen Elizabeth II Conference Centre, London, UK the Finch report, but the importance of charlesdarwinhouse.co.uk), where servants and others who have to publication income to learned societies we will share facilities with the Society respond quickly to concerns. All The gut microbiota is the focus of this event, with this symposium will provide a platform for young in supporting training and conference of Biology, the Biochemical Society, members of the Houses of Commons international experts presenting the latest fi ndings investigators and established scientists to present activities may not be fully understood the Society for Experimental Biology and Lords and elected members of the about its genomics and physiology, as well as the their latest basic and clinical fi ndings on the gut by many proponents of OA. The SGM and the British Ecological Society. The devolved administrations receive copies dynamic, metabolic and immunological aspects of microbiota and probiotics. This will be a unique Policy Committee recently contributed restructured publications department of all briefing notes and are invited to its interaction with the host in the context of health opportunity to engage in an international and high to the Society of Biology submission will be the first to move, beginning in receive Microbiology Today. and disease. Related to this, the potential infl uence level scientifi c debate on this exciting fi eld of to the House of Lords inquiry into OA February, with other staff following over This issue of Microbiology Today of probiotics on the composition and function of research, and to exchange opinions on the current publishing. the course of the year. The argument celebrates the award of the SGM Prize the microbiota will also be discussed. As always, knowledge on gut microbiota and probiotics. The new Council Committees for the Society to be located outside Medal to Professor Harald zur Hausen. have begun to meet and to implement London to reduce costs is no longer It is a mine of useful information Registration Fee Until 1st March 2013 From 2nd March 2013 the Strategic Plan 2012–17. This is valid, and London provides a bigger about the relationship between viruses and cancer, and will be circulated to Delegates €100.00 €150.00 available on the SGM website at www. pool of the specialist staff that a sgm.ac.uk/about/SGM_Strategic_ modern learned society needs. health professionals, as well as to Students (Including PhD students) 50.00 75.00 € € Plan.pdf. We are beginning to look at I encourage all members to SGM members and politicians. The Approved by the Society of Biology for purposes of CPD (18 credits), and by the Institute of Biomedical Science (10 credits). many of the activities that the Society promote microbiology, not only in SGM Prize Medal is the premier award of the Society and I am pleased to Considering submitting a poster? Registration fee will be undertakes. There is opportunity for the scientific community, but with waived for one author of posters selected for presentation all Ordinary Members of the Society politicians and other opinion-formers. congratulate Professor zur Hausen to involve themselves more directly in 18 November 2012 was European and our other prize winners, details of the work of the SGM through standing Antibiotic Awareness Day and one whom can be found on pages 8 and 9. for election as members of Council or letter to a local MP, pointing out the of Divisional Committees. Details are issues around the small number of NIGEL L. BROWN, President available on pages 9 and 10. usable antibiotics and the relative Email [email protected] The major structural change for lack of investment in discovering new the Society will be relocation of its antimicrobials, led to action. The offices to London. We have found MP tabled a question with the

4 Microbiology Today Feb 2013 Microbiology Today Feb 2013 5 News

News of Members Publication in New COUNCIL MEMBERS Andrew Davison Congratulations to Professor James Prosser, University of Microbiology is now free! Andrew Davison has worked in Glasgow Sara Burton Aberdeen, on the award of an OBE in the New Year Honours List since 1976, except for a couple of years SGM’s original journal, Microbiology, is offering for services to environmental science. After attending a local off (for good behaviour) that were another benefit to authors – completely free comprehensive school spent in Bernie Moss’ lab at the NIH in The Society notes with regret the passing of Dr Christopher K. publication! All papers accepted since December in Oxfordshire, Sara the mid-1980s. In 1991, he became a BOSMAN (member since 2000). 2012 will be published completely free of completed her BSc(Hons) Programme Leader at the MRC Virology charge. Editor-in-Chief, Agnès Fouet, says, ‘I am in Applied Biology at Unit, which was recently absorbed into Vouchers for mobiles really pleased that we have made publication in Bradford University (1984) the MRC–University of Glasgow Centre Microbiology free. Authors can convey their full An article in the August 2012 issue of Microbiology Today which incorporated a for Virus Research. His expertise is in viral report in a well-respected journal that maintains (vol. 39, part 3, 143) announced the introduction of mobile- very inspirational year at genomics, with a focus on herpesviruses high-quality production standards.’ optimised sites for SGM’s four journals, Microbiology the National Collection and, more specifically, human (m.mic.sgmjournals.org/), JGV (m.vir.sgmjournals.org/), IJSEM Microbiology has a far-reaching readership – all papers of Industrial and Marine cytomegalovirus. He has played an active (m.ijs.sgmjournals.org/) and JMM (m.jmm.sgmjournals.org/). are freely available online 12 months after publication Bacteria Ltd in Aberdeen. After working for 4 years in part in the SGM for many years, having been on the Virus Group – and is well cited, with an impact factor of 3.061. A voucher service for each mobile site is now in place. a University of Cardiff spin-out company (Biotal Ltd), Committee in the 1990s and more recently on the Virology Division. Papers receive fast and high-quality review; a first This enables users belonging to a subscribing institution to Sara undertook a PhD at Exeter in plant molecular He was an Editor of the Journal of General Virology from 1999 to decision from expert international editors is reached link their mobile device to the journals, allowing access to biology. After a career break, during which time she 2005. Now that his four children have at last (almost) left home, he within 4.2 weeks, on average. The journal’s research is embargoed content when not on the institution’s network. taught for the Open University and had two sons, Sara has taken up his boyhood hobby of breeding exotic moths. relevant to and cited by the microbiology community, To obtain a code, users should returned to Exeter University where she worked in the and could be the ideal place for your next research Environmental Microbiology Research group. Recently, connect to their institution’s Maggie Smith paper, whether you are a new or returning author. network, select ‘Authorize she has moved to Education and Scholarship and now enjoys her Maggie did her BSc at this Device’ on the mobile role as Senior Lecturer and Senior Tutor in Biosciences. You can hear more about the benefits of publishing the University of Leeds site and follow the in Microbiology by watching the Editor-in-Chief’s in Biochemistry and instructions. The code video (www.youtube.com/embed/t6QRCAu2f7E). Charles Penn Microbiology and a needs to be applied to the You can also find out more about the journal, Charles trained in Biochemistry at the University of Liverpool PhD in Bristol under the device within 48 hours. Each including how to prepare and submit a manuscript in the late 60s, did his PhD work in bacterial veterinary vaccine supervision of Professor mobile device must be vouched for publication, by visiting the journal website development at the Wellcome Foundation labs in Beckenham, Kent, Ian Chopra. She then for individually. (http://mic.sgmjournals.org). and went on to join Harry Smith in Microbiology, now subsumed went back to Leeds to into Biosciences, at the University of do a 5-year postdoc with IJSEM NEWS Birmingham where he has remained. the late Professor Simon A project is underway at SGM Publishing to reduce the time from acceptance to print Charles’s research career has focussed Baumberg and this was followed by a 3-year, semi- publication for papers in the International Journal of Systematic and Evolutionary Microbiology on bacteria as pathogens with a independent postdoc position with Professor Iain (IJSEM). Although authors’ accepted manuscripts are available online as ‘Papers in Press’ within molecular perspective. Organisms Hunter at the University of Glasgow. Maggie gained a week, final print publication (as required for valid publication of bacterial names) has been he has engaged with include her first lectureship at the University of Stirling, but slow. Starting with the January 2013 issue, larger issues will be printed to reduce the waiting Neisseria, spirochaetes, Helicobacter, then moved to Nottingham University where she time for authors. Papers describing eukaryotic taxa that are not covered by the Bacteriological Campylobacter and E. coli. He has stayed for 10 years and was awarded a personal chair Code have been fast-tracked during 2012 and are now published quickly. extensive experience in journal in January 2003 before moving to the University of editing, as an Editor of FEMS Letters, Aberdeen. This year, Maggie moved again to the We would like to thank IJSEM authors for their patience and look forward to delivering much Microbiology and, latterly, the Journal of Biology Department at the University of York; here faster publication by mid-2013. Medical Microbiology as Editor-in-Chief. she holds a Chair in Microbiology.

6 Microbiology Today Feb 2013 Microbiology Today Feb 2013 7 SPRING CONFERENCE PRIZE LECTURERs peter wildy prize for FLEMING prize Help shape the future of SGM microbiology education ROBERT RYAN If you are an Ordinary Member, please consider SGM Prize MEdal David Bhella Wednesday 27 March 12:10–12:50 putting yourself forward to join Council and have a Harald zur Hausen Monday 25 March 17:20–18:05 Cyclic di-GMP signaling and the bigger say in how your Society develops. regulation of bacterial virulence Tuesday 26 March 12:10–12:50 Beautiful and a little bit scary … viruses and There is one vacancy for an Elected Member to Infections causing human cancers: science communication Robert gained his PhD in Molecular serve on Council from Sept 2013 until Sept 2017. why do some ubiquitous infections David is a programme-leader in the MRC Centre Microbiology with David Dowling, followed Council has formal meetings four times a year. In by a postdoc position with Max Dow in mainly cause regional cancers? for Virus Research (Glasgow). His research focuses addition, Elected Members have an important role Cork. Thanks to a number of fellowships Harald studied Medicine at the on the structural biology of viruses and virus–host to play in several of the Committees that influence he has been lucky enough to work in Universities of Bonn, Hamburg and interactions. He has a long-standing interest in public different aspects of SGM business, such as the laboratories of Ute Romling (Karolinska Institute), Chuck Farah Düsseldorf and received his MD in engagement and working publications, finance, policy, conferences, (São Paulo), George O’Toole (Dartmouth, USA) and Judy Armitage 1960. After his internship, he worked as with school audiences to communications and professional development. (Oxford). In 2009, he started his own group in Cork after receiving a postdoc at the Institute of Microbiology enthuse students about Committee meetings often take place in addition Science Foundation Ireland Starting Investigator award. Recently, he in Düsseldorf, and subsequently in the Virus Laboratories of the careers in the sciences, to formal Council meetings. Council Members are was awarded a Wellcome Trust Senior Research Fellowship to relocate Children’s Hospital in Philadelphia where he was later appointed particularly microbiology. encouraged to participate in SGM conferences where his group to Dundee. His work centres around understanding the Assistant Professor. After a period of 3 years as a senior scientist Over the past decade, the cost of attendance is supported by the Society. he has built a thriving role that interspecies signalling plays in influencing both bacterial at the Institute of Virology of the University of Würzburg, he SGM, under Council’s guidance, is undergoing a programme of outreach virulence and response to therapy in polymicrobial infections. was appointed in 1972 as Chairman and Professor of Virology period of significant change in line with the new activities in partnership with at the University of Erlangen-Nürnberg. In 1977, he moved to strategy (www.sgm.ac.uk/about/objectives.cfm) Glasgow Science Centre. COLWORTH PRIZE a similar position at the University of Freiburg. From 1983 to and we would like to recruit a new Council Member 2003, he was appointed as Scientific Director of the Deutsches JEFFREY W. ALMOND willing to commit the time and with the skills and Krebsforschungszentrum (German Cancer Research Centre) in HOT TOPIC Monday 25 March 12:10–12:50 experience to make a positive contribution to the Heidelberg. He retired from this position in 2003. Paul W. O’Toole Vaccines R&D: challenges for the strategy through one or more of the Committees. He has received numerous prestigious national and international Tuesday 26 March 21st century If you would like to contribute, we would very much awards, including the Nobel Prize for Medicine 2008, the Life 17:35–18:05 Jeffrey is the Head of Discovery Research like to hear from you. Alternatively, you may want to Science Achievement Award of the American Association for The human microbiome: and External R&D at Sanofi Pasteur, the encourage a colleague to get involved. Nominations Cancer Research, the German Special Order of Merit with Star and overdue recognition for largest manufacturer of human vaccines. should come from individuals who have been an 24 honorary MD and PhD doctorates. He is an elected member of our fellow travellers He is responsible for Sanofi Pasteur’s Ordinary Member for at least 2 years and must be various academies and research organisations, and has become an Paul obtained PhD at Trinity portfolio of exploratory projects aimed at providing pre-clinical proof- supported by two other Ordinary Members. Please Honorary Member of a number of biomedical scientific societies. College Dublin. Following of-concept for a range of human vaccine targets. He also identifies use the nomination form at www.sgm.ac.uk/about/ A large number of Special Lectures and Visiting Professorships, research in Sweden, Canada, New Zealand and the and assesses opportunities for external collaboration on vaccine objectives.cfm and include information about Memberships of Editorial Boards and active involvements in the USA, Paul is now Professor of Microbial Genomics at targets and relevant technologies. Before joining Sanofi Pasteur in the skills you can offer and how you would like to organisation of international meetings complement his CV. University College Cork, Ireland. His main research 1999, Jeffrey was Professor of Microbiology at Reading, and served contribute to Council. Please send your nominations From 2000 to 2009, he was Editor-in-Chief of the International theme is the genomics and metagenomics of in various offices, including Chairman of the Virology Division of to [email protected] Journal of Cancer, and from 2006 to 2010 he was member of gastrointestinal bacteria with emphasis on human- the IUMS, SGM International Secretary and member of the UK the Board of Directors of the International Union against Cancer. associated species and host interaction, particularly governmental Spongiform Encephalopathies Advisory Committee. The closing date is 30 April 2013. Informal enquiries From 2003 to 2010, he was Vice-president of the German National commensal lactobacilli. His latest research examines He is currently a member of the Medical Research Council and an about the role of elected Council Members can be Academy for Natural Sciences and Medicine. In 2010, he was the composition and function of the gut microbiota, elected fellow of the UK Academy of Medical Sciences. He has made to Simon Festing ([email protected]). If appointed Chairman of the Scientific Council of the National its dependence on diet, and its relationship to health, published numerous articles in the field of microbiology, especially the number of nominations exceeds the number of Science Transfer and Development Agency in Bangkok, Thailand. ageing and well-being in humans and animals. on influenza and picornaviruses, HIV and vaccines. vacancies, an election will be held in early summer.

8 Microbiology Today Feb 2013 Microbiology Today Feb 2013 9 SGM Conferences – Come and help Heatley-Payne and Hayes-Burnet Your chance to get involved us give bacteria Award Recipients Announced SGM Divisional Committees are looking for enthusiastic volunteers who would like to the brush off! The Heatley-Payne and Hayes-Burnet Awards are offered jointly participate in planning and delivery of scientific conference programmes. Members of the with the American Society for Microbiology (ASM) and Australian As Big Bang returns to London’s Divisional Committees have an interest in an aspect of one of four cross-cutting themes: Society for Microbiology. The awards provide funds to support the Excel Centre, SGM will be there! Microbial diversity & evolution; Fundamental microbiology; Translational microbiology; and reciprocal exchange of one early-career Society member to present Infectious disease. School members, and anyone their research at the other Society’s main annual conference and with interested children, are invited to visit an institution in that country, Divisions meet twice each year and work independently to plan some conference symposia whilst to come along and take part in our enabling the recipient to raise their others are developed with a cross-cutting theme in mind. Each member serves on the committee ‘hands-on’ investigation into the profile among the microbiology for 3–4 years and is expected to contribute actively to Divisional Committee business. An importance of oral hygiene on our community and to initiate and individual will usually participate in the planning of several symposia over their term of office and stand Plaque attack: giving bacteria strengthen collaborations. would be likely to take the lead in organising the programme for at least one event. the brush off. The recipient of the 2013 SGM Heatley- If you would like to make a contribution to SGM conferences we would very much like to hear We are very grateful to Nicola Stanley- Payne Award is Dr Siobhan Watkins from you. Alternatively, you may want to encourage a colleague to get involved and support Wall for her help in developing this (left) of University of Portsmouth, who their nomination. activity. will attend the ASM General Meeting in Denver Divisional Committee Elections 2013 and visit the University of Maryland to further her research on For the 2013 elections, we are inviting nominations to fill 9 vacancies (see below). freshwater cyanophages from the south of England. Dr Barry Johnson (right) of National Institutes of Health is to receive the Theme Virology Prokaryotic Eukaryotic Irish Division reciprocal American Society for Microbiology award. Barry will visit Microbiology Microbiology Peter Cherepanov of Cancer Research UK London Research Institute Microbial diversity 2 vacancies 1 vacancy No vacancy 1 vacancy and present his work on modelling and & evolution inhibition of HIV-1 integrase at the SGM Fundamental No vacancy 1 vacancy No vacancy Spring 2013 Conference. microbiology The SGM Hayes-Burnet Award for 2013 Translational No vacancy 1 vacancy 1 vacancy has been awarded to Dr Rebecca Sumner (left) of University microbiology of Cambridge. Rebecca will visit Associate Professor David Infectious disease 1 vacancy No vacancy 1 vacancy Tscharke at the Australian National University and then attend the Annual Scientific Meeting in Adelaide. Nominations for the Virology, Prokaryotic and Eukaryotic Microbiology Divisions must fall into the cross-cutting At the University, she will deliver a themes as advertised. The Irish Division does not have cross-cutting themes so nominations are open to seminar on her research and receive individuals with any scientific interest. training in analysing adaptive and memory immune responses Nominations should be made using the form available on the SGM website: www.sgm.ac.uk/meetings/ of vaccinia virus in a murine model. The Australian recipient is divisions.cfm. All nominees must be SGM Members and the nomination must be supported by two Ordinary Dr Johanna Kenyon (right), University of Sydney. Johanna will Members. If the number of nominations exceeds the number of vacancies, elections will be held in late spring. join us at the SGM Autumn 2013 Conference and visit Professor Please send your nominations to [email protected]. The closing date is 30 April 2013. Gordon Dougan of the Wellcome Trust Sanger Institute as part of More information about the Divisional Committees and their current members is available at www.sgm.ac.uk/ an ongoing collaboration on the capsule locus in Acinetobacter meetings/divsions.cfm baumannii genomes.

10 Microbiology Today Feb 2013 Microbiology Today Feb 2013 11 conferences

SGM Spring Conference 25–28 March 2013 SGM Autumn Conference 2–4 Sept 2013

The Autumn Conference will take place at the University of Manchester Central Convention Complex – www.sgmmanchester2013.org.uk Sussex, located near the seaside town of Brighton, famed for its With just under a month until the Spring Conference 2013 there is still time to register and cafes, the historic Lanes, and the world famous Royal Pavillion. be part of this international event. For the latest programme details and to book online, visit This exciting conference will appeal to both bacteriologists and www.sgmmanchester2013.org.uk – see you there! eukaryotic microbiologists from a variety of different backgrounds, especially those interested in infectious disease. Symposia over the Conference snApShot Networking workshop and supper for three days will cover many different areas of microbiology research. early-career delegates (24 March) Viruses and human cancer: causes to cures (25–26 March) Impact of bacteriophage in the environment will cover the Viruses are associated with the development of about 11% of all The workshop brings together early- increasing awareness and impact of bacteriophage on the ecology of human cancers, with the incidence of the majority of these occurring career delegates before the start of the the biosphere, while Microbial modulation of cellular responses in developing regions of the world. The International Agency for conference. Delegates who attend get will highlight the way different bacterial toxins and effectors subvert, Research on Cancer has defined seven viruses as carcinogens; the to know some friendly faces and pick up inhibit or activate host-cell pathways to the benefit of pathogens. herpes viruses Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpes tips and advice on making the most of Pathogen genomics – current clinical applications will show how virus (KSHV), high-risk human papillomaviruses (HPV), human T cell networking opportunities in the coming clinical practice is changing based on the data generated by next- lymphotrophic virus (HTLV-1), hepatitis B and C viruses (HBV and HCV) days. The session costs £13, includes generation sequencing technology, and Regulatory phosphate- and human immunodeficiency virus type 1 (HIV-1). New associations supper and can be booked when based molecules will outline progress in understanding the actions between viruses and cancers are emerging, for example Merkel cell registering to attend the conference. of phosphate-based regulatory molecules. polyomavirus (MCPV) and the role this virus plays in the development prize lectures SGM and the British Society for Medical Mycology are hosting a joint of Merkel cell carcinoma. symposium on Fungal diseases, diagnosis and drug discovery. For biographies of the speakers, see Some types of adenovirus and polyomavirus have been found to The programme spans contributions from world-leading scientists on pp. 8–9. induce tumours in rodents; these have provided invaluable model the major human fungal pathogens, such as Aspergillus, Candida, systems to study mammalian tumorigenesis. Oncolytic viruses have GRANTS Cryptococcus, dermatophytes and plant pathogens, as well the latest also been exploited as novel therapies for the treatment of cancers. Grants are available to eligible diagnostic techniques and advances in drug discovery. Microbial Why attend – Associate Postgraduate Student survival in the host will showcase the diverse strategies mounted by The aim of this symposium is to realise the impact of virus infection on Members fungal and parasitic pathogens to survive within the human host. the incidence of human cancers worldwide, to gain an understanding – Associate Members who are Brighton beach and pier. Registration and abstract submissions will open shortly. Keep an eye Brighton Royal Pavillion. of the mechanisms underlying virus-associated cancers and to technicians iStockphoto / Thinkstock on the SGM website and e-newsletter for the latest details. iStockphoto / Thinkstock appreciate the issues surrounding treating and preventing them. It will – Retired members focus on the epidemiology and the pathogenesis of cancer-causing 3rd Oxford Bone Infection Conference EMBO Workshop on Integrating – Qualifying Undergraduate student Save the dates 28 March–1 April 2013 Omic Approaches to Host–Pathogen viruses, host–virus interactions, the therapeutic exploitation of viruses members to treat cancers, and the current state of play in the development of SGM Spring Conference 2014 Oxford Town Hall, Oxford Interactions Apply online at www.sgm.ac.uk/grants/ vaccines and other novel antiviral therapies. Arena and Convention Centre, www.hartleytaylor-registration.co.uk/ 25–27 June 2013 The symposium will be perfectly complemented by this year’s Manchester town hall. Liverpool docs/OBI0flyer.pdf Radisson Blu Hotel, Liverpool iStockphoto / Thinkstock SGM Prize Medal lecture (26 March at 12:10) from Nobel Laureate 14–17 April 2014 www.embo.org/events/calendar.html Merkel Cell Carcinoma: Professor Harald zur Hausen, who received his Nobel Prize in Other SGM-sponsored meetings New Insights & Emerging Therapies 14th International Conference on 2008 for his work establishing the role of papillomaviruses in the British Yeast Group Meeting 2013 7 May 2013 Pseudomonas 2013 development of cancer of the cervix. 20–22 March 2013 Edinburgh International Conference 7–11 September 2013 Britannia Hotel, Nottingham Centre Lausanne, Switzerland For details of other exciting symposia and workshops, visit the www.britishyeastgroup.org www.iid2013.org/satellite-meetings www3.unil.ch/wpmu/pseudomonas2013 conference website www.sgmmanchester2013.org.uk

12 Microbiology Today Feb 2013 Microbiology Today Feb 2013 13 micro shorts

VSV particles (purple) budding from a cell (green). Steve Gschmeissner/ Science Photo Library

Viruses and cancer Water buffalo. Stockbyte / Thinkstock The development of cancer is a multistage process In many cases where there is a strong association Papillomavirus infection- and it is clear that infectious agents either directly of a particular virus with a tumour, the function and linked cancer in fern-grazing cause or are strongly associated with up to 17% of significance of virus-encoded gene products expressed malignancies in the developed world. Viruses play in transformed cells is poorly understood. In addition, buffalo a significant role by directly causing aberrant cell little is known of the environmental co-factors or Bovine papillomavirus may infect over 90% growth through the action of transforming genes, host genetics that may predispose to virus-associated JGV of buffaloes grazing on ferns in Turkey. Ingesting the establishment of chronic inflammatory processes cancers, and the existence of a ‘hit-and-run’ ferns is thought to trigger papillomavirus BPV-2 or virus-induced immunosuppression that predisposes mechanism of virus-induced oncogenesis has few activation, leading to cancerous growth, perhaps to oncogenesis, or the provision of a critical first ‘hit’ proponents and is deserving of further scrutiny. through suppression of the buffalo immune response. Battling cancer in the multistage oncogenic process. From a different perspective, in recent years In addition, BPV-2 has been clinically detected in with viruses cancerous bladder tissue specimens from buffaloes. Vaccination against certain viruses has proven considerable effort has been placed in the The use of viruses specifically to kill BPV-2 infection promotes induction of the E5 beyond any question that certain cancers are development of viruses as potential treatments cancer cells is an increasingly emerging oncoprotein, promoting cancerous cell growth. preventable, as exemplified by the success against human cancers, based on either the delivery JGV area of research due to the impaired Fluorescently imaging these proteins on tumour of vaccination against hepatitis B, preventing of ‘suicide’ genes, the development of genetically ability of many cancer cells to clear samples by microscopy showed the platelet-derived hepatocellular carcinoma, and human papillomavirus manipulated viruses that selectively replicate in virus infection. Research outcomes have growth factor (PDGF- ) receptor interacting with in the case of cervical carcinoma. In the veterinary transformed cells or the development of viruses with β been so successful that one virus has E5 and BPV-2, again providing evidence of BPV-2 arena, vaccination of chickens against Marek’s disease selective tropism for tumour cells. The development already been approved for clinical use involvement in virus-induced cancers. The association virus (an oncogenic herpesvirus) has proven efficacy of oncolytic viruses shows considerable promise as in China. Researchers at the University between fern ingestion and papillomavirus infection in preventing lymphomas. Nonetheless, there is evidenced by the increasing number of clinical trials of North Carolina discuss the potential has also been seen in humans who have developed much to be done. currently in progress. of a widely studied virus, Vesicular throat cancer in Brazil. It is economically important in Stacey Efstathiou Editor-in-Chief, JGV stomatitis virus (VSV), to be used as an farming to understand the strategies that BPV-2 anti-cancer agent in a recent review. papillomavirus uses to cause cancer in cattle and VSV causes infections in animals, buffalo. Discovering more about the 189 types of Fighting lung cancer with viruses including horses, but is generally papillomavirus and their ability to infect other Viruses could help control certain fast-growing lung cancer cells, according asymptomatic in humans. So far, VSV animal species could lead to potential preventative to researchers at Johns Hopkins University. In recent years, Seneca Valley virus has been genetically modified to reduce strategies and treatments. – which selectively targets cancerous cells but not normal somatic cells – has toxicity and increase selectivity of killing shown promise as a potential anti-cancer treatment. However, some types of J Gen Virol doi:10.1099/vir.0.047662-0 JGV cancer cells. One such VSV strain has aggressive ‘small cell lung cancer’ have previously been thought to be resistant Rebecca Way University of Aberdeen been developed to encode interferon, to infection. By manipulating the viral genome to produce a green fluorescent Cancerous cells from the which enhances the immune system to ‘reporter’ protein, the researchers found that a small sub-population of these bladder of a water buffalo. improve oncoselectivity. It has shown cancer cells is in fact highly susceptible to the virus. The researchers also Dr Sante Roperto, Università di so much promise that a phase 1 clinical Napoli Federico II, Italy confirmed that only cancerous cells were targeted: when they infected tumour- trial is now underway. With some fine bearing mice with the virus, it did not replicate in normal tissues. The ability to tuning of oncolytic properties, VSV may infect only a subset of tumour cells could prove useful in anti-cancer treatments. soon be used alone or as an adjunct to For example, viruses could be used to deliver toxins to specific cancer-affected current therapies to fight cancer. regions of the body. J Gen Virol doi:10.1099/vir.0.046672-0 Chest X-ray showing lung cancer. J Gen Virol doi:10.1099/vir.0.046011-0 Naomi Osborne Thermo Fisher Photodisc / Thinkstock Adam Kucharski Imperial College, London Scientific

14 Microbiology Today Feb 2013 Microbiology Today Feb 2013 15 Introducing viruses and cancer

Laura N. Hindle & David J. Blackbourn iStockphoto / Thinkstock either by vaccinating people against The concept of behavioural and ideas founded the modern cellular theory Almost 1 in 5 cancers are caused by the oncogenic agents, preventing their environmental risk factors influencing of cancer. infection, or by treating the infections cancer development dates back hundreds infectious agents, the majority of which are before cancer develops. Second, the of years. In 1714, Bernardino Ramazzini Discovering tumour study of oncogenic viruses can and has noted that nuns developed less cervical viruses viruses. In this article, the authors present an provided a route to understanding the cancer (but more breast cancer) The origins of virology date back to the biology of cancer cells. compared to the general population. end of the 19th century, with Beijerinck overview of cancer and tumour virology to The importance of this observation is studying tobacco mosaic disease in plants Discovering cancer reflected in the fact that cervical cancer is and Loeffler and Frosch working on the complement the accompanying articles in Although cancer was less common now recognised as a sexually transmitted aetiology of foot-and-mouth disease. before the 20th century, it is certainly not disease, being caused by HPV, a sexually Around a decade later, the theory that this issue. a new disease. The paleoanthropologist transmitted virus. Ramazzini’s work viruses might cause certain cancers began Louis Leakey discovered the first is one of the first great epidemiologic to emerge, but it took many years for this At the Spring 2013 SGM development of human papillomavirus developing countries, this frequency rises known case of homonid cancer in an studies and demonstrates the value of idea to become widely accepted. Ellerman conference, viruses and cancer (HPV) vaccines that are expected to almost 1 in 4. The majority of these archaeological jawbone, which was epidemiology in helping to identify risk and Bang published observations on will be emphasised with a symposium to reduce the global burden of cancer of cancer-inducing (oncogenic) infectious suggestive of Burkitt’s lymphoma factors in cancer. Subsequently, Percival the viral transmission of leukaemia in entitled ‘Viruses and cancer: causes to cures’. the cervix. agents are viruses, the subject of the occurring at least 300,000 years ago Pott described in 1755 an occupational chickens in 1908 and, in 1911, Peyton This symposium will be complemented Over one in three people in the present article. Rob Newton provides (see timeline on p. 19). cancer of the scrotum in chimney sweeps, Rous reported on sarcoma in chickens by the pre-eminent SGM Prize Medal UK will develop cancer during their more insight into the incidence of virus- The first contemporary caused by their chronic exposure to soot. being caused by what later became known Lecture, to be given by Harald zur lifetime. Yet far fewer of us are aware associated cancers in the following article documentation of cancer can be traced In 1838, German pathologist as Rous sarcoma virus (RSV). He found Hausen (pp. 8 & 48). Professor zur of the association of viruses with cancer (p. 22). back thousands of years to the ancient Johannes Muller demonstrated that that he could transfer the sarcoma to Hausen was awarded the 2008 Nobel development. Globally, the latest figures In considering the global Egyptians in 3000–1500 BC. In several cancer is made up of cells, while his other chickens by their inoculation with a Prize in Physiology or Medicine ‘for his indicate that of the 12.7 million cases burden of human cancer, these figures Egyptian medical manuscripts, such as student, Rudolph Virchow (1821–1902), cell-free filtrate of the tumour. His work discovery of human papillomaviruses causing of cancer occurring annually, 16% are significant for two reasons. First, the Edwin Smith papyrus, a description concluded that all cells, including cancer was widely discredited at that time, but in cervical cancer’. In turn, his work led to the are attributable to infectious agents. In these cancers are potentially preventable of cancer can be found. cells, are derived from other cells. These the decades that followed more tumour

16 Microbiology Today Feb 2013 Microbiology Today Feb 2013 17 Discovering cancer Human tumour viruses 1801–1858 300,000 BC 1964 1994 Johannes Müller Homonid EBV, the first human Yuan Chang & Patrick Moore with tumour virus discovered by discover KSHV Burkitt’s Antony Epstein & Yvonne Barr lymphoma 1968 Cellular theory of cancer HBV discovered. Linked to HCC in 1975 1714 Bernardino Ramazzini 1980 The beginnings Robert Gallo & of epidemiology 1821−1902 colleagues identify 2008 HTLV-1 Rudolph Virchow Chang & Moore discover MCV viruses were discovered (see timeline). means that it encodes an enzyme activity and Yvonne Barr visualised herpesvirus- This accumulating evidence began to to reverse transcribe its RNA genome into like particles in cells from endemic change opinions and, in 1966, Rous was a ‘proviral’ DNA copy that integrates in (i.e. occurring in individuals of African 1755 1933 onwards 1980 1989 awarded the Nobel Prize in Physiology or to the host chromosomal DNA. It was origin) Burkitt’s lymphoma – the same Percival Pott More and more animal HBV vaccine implemented HCV and its link to Medicine ‘for his discovery of tumour-inducing complicit in the award of yet another tumour recognised by Louis Leakey Occupational cancer tumour viruses discovered hepatocellular carcinoma viruses’, pioneering work he began over 50 Nobel Prize in Physiology or Medicine in 1932. This virus was later found to in chimney sweeps discovered by Michael Houghton years earlier. to Howard Temin and David Baltimore be a novel herpesvirus and was named 1911 3000–1500 BC Peyton Rous The discovery of RSV led to the (with Renato Dulbecco) in 1975 for Epstein–Barr Virus (EBV). The link Edwin Smith The transfer of a 1983 identification by Harold Varmus and their discovery of this enzyme activity: between EBV and Burkitt’s lymphoma papyrus sarcoma to chickens High risk HPV strains Michael Bishop of the src gene that is reverse transcriptase. was met with scepticism initially, as First documentation by cell-free tumour identified by Harald responsible for RSV-induced tumours. EBV is insufficient to cause lymphomas: of cancer extracts zur Hausen They showed that src was a derivative of Human tumour viruses approximately 90% of the population Discovering tumour viruses a normal cellular gene. This discovery Several types of viruses are now known is infected with EBV. However, of a cellular gene with cancer-inducing to be associated with the cause of human overwhelming evidence now supports the correlating reduced HBV infection and Viruses and cancer timeline. Images: skull, Digital Vision/Thinkstock; Ramazzini, Pott, Smith papyrus potential (or proto-oncogene) was cancers. Indeed, according to Harald causal association of EBV with endemic decreased HCC incidence in Taiwan & Gallo, public domain; Müller & Virchow, US National Library of Medicine; Rous, NYPL/Science Source/ noteworthy because it indicated that some zur Hausen, viruses confer a risk of Burkitt’s lymphoma, and EBV is now provided the essential epidemiological Science Photo Library; Epstein, Prof. Sir Anthony Epstein CBE FRS, Wolfson College, Oxford; zur Hausen, tumours can develop by the aberrant developing cancer second only to smoking also associated with Hodgkin lymphoma link between the virus and the tumour. Armin Kübelbeck; Chang & Moore, I. Atherton, SGM; Houghton, © University of Alberta expression of cellular genes responsible tobacco. The mechanisms by which they and nasopharyngeal carcinoma (NPC), In 1989, Michael Houghton and for controlling the mechanisms by which do so are beyond the scope of this article, amongst others. Indeed, Harald zur his team discovered hepatitis C virus malignant lesions, suggesting that leukaemia (ATL). This virus is endemic cells either divide or die. Expression of the but some of the accompanying articles Hausen’s work contributed to the (HCV) during their studies of non-A, these viral proteins were responsible in certain geographic regions, such oncogene (a mutant of a proto-oncogene) address this topic. The known oncogenic recognition of the role of EBV in non-B hepatitis. The World Heath for the malignancy. In 2008, the year as southern Japan and central Africa. then permits cell division to proceed human viruses are listed in Table 1 and Burkitt’s lymphoma and NPC. Graham Organization estimates that there are of Professor zur Hausen’s Nobel Prize, However, as with infection with so many unchecked. For this discovery, Varmus described briefly below. Taylor and James Turner discuss EBV more than 170 million people chronically anti-HPV vaccines were introduced into oncogenic viruses, only a proportion and Bishop were awarded the 1989 Nobel in more detail in the accompanying infected with HCV who are at risk of the UK for school-age girls with the aim (1–4%) of infected individuals will Prize in Physiology or Medicine ‘for their EBV article (p. 34). developing liver cirrhosis and HCC. Jane of preventing their infection with the develop ATL and the onset of disease can discovery of the cellular origin of retroviral The first human tumour virus was Since the discovery of EBV, McKeating and Colin Howard discuss so-called high-risk strains of the virus, take decades. HTLV-1 can also cause a oncogenes’. RSV is a retrovirus, which discovered in 1964 when Tony Epstein strong evidence for five other viruses HBV and HCV in their accompanying thereby reducing the incidence of cancer non-malignant, progressive neurological being associated with the development article (p. 30). of the cervix. Sally Roberts and Jo Parish disease called HTLV-1-associated Table 1. The seven human oncogenic viruses and the major malignancies with of human cancers has accumulated, and provide further information on HPV in myelopathy (HAM) or tropical spastic which they are associated. a sixth virus, Merkel cell polyomavirus HPV their accompanying article (p. 26). paraparesis (TSP). HTLV-1 transforms (MCPyV), is likely to be added to the list In the early 1980s, Harald zur Hausen cells into a malignant state through the Virus Malignant disease (see Table 1), equating to seven oncogenic identified novel strains of HPV DNA in HTLV-1 action of the Tax protein. Tax has a Epstein–Barr virus Burkitt’s lymphoma; Nasopharyngeal human viruses. cervical cancer biopsies. Thus, in 1983 Since RSV, the first oncogenic virus multitude of activities, including being carcinoma; Hodgkin lymphoma his lab isolated HPV type 16 (HPV-16) discovered, is a retrovirus, the potential able to transform human T-cells by Hepatitis B virus Liver cancer HBV & HCV in ~50% of the biopsies and in 1984 of retroviruses to cause cancer in humans transactivating various cellular promoters, Human papillomavirus Cervical cancer Hepatitis B virus (HBV) was discovered he reported HPV-18 in ~20%. The has been of great interest and under such as those of cytokines and cytokine Human T-cell leukaemia virus type 1 Adult T-cell leukaemia in 1968 and linked to the development importance of these viruses in the cause intense investigation. The identification receptors, leading to signalling cascade Hepatitis C virus Liver cancer of hepatocellular carcinoma (HCC) in of cervical cancer was demonstrated by of human T-cell leukaemia virus type 1 activation. the frequent clonal integration of their (HTLV-1) in cutaneous T-cell lymphoma Kaposi’s sarcoma-associated herpesvirus Kaposi’s sarcoma; Primary effusion 1975. Subsequently, an HBV vaccine lymphoma was developed to protect against HBV genomes in the tumour cells, suggesting in 1980 by Robert Gallo and colleagues KSHV the viruses were driving the proliferation provided one opportunity to analyse the Kaposi’s sarcoma (KS) was first described Merkel cell polyomavirus* Merkel cell carcinoma infection and was implemented in 1980. It is still in use today and was the first of the malignant cells. Moreover, two role of this retrovirus in human disease in elderly Mediterranean men in 1872 by *A causal association between Merkel cell polyomavirus and Merkel cell carcinoma has yet to be vaccine to prevent the development of HPV genes, E6 and E7, were always development. It is now recognised as Moritz Kaposi. The lesions are unusually formally established. a specific human cancer. The early studies expressed in the tumours and in pre- the aetiological agent of adult T-cell angioproliferative and inflammatory

18 Microbiology Today Feb 2013 Microbiology Today Feb 2013 19 Are there other human viruses” yet to be discovered that can therefore be targeted to provide hope in the treatment and prevention of their respective tumours?” in nature. It was originally a quite rare [e.g. latency-associated nuclear antigen track record in causing tumours, though cancer, also seen in certain individuals (LANA) and viral cyclin, as well as virus- not necessarily in humans. living in Africa and in organ transplant encoded microRNAs] are expressed In recognition of their considerable recipients. However, its appearance during latency drive cell proliferation contributions to tumour virology, by in young gay men during the 1980s and inhibit apoptosis. KSHV lytic their discovery of two novel viruses and coincided with the beginning of the proteins (e.g. a viral cytokine and viral their contributions to understanding the AIDS pandemic and it is now an AIDS- chemokines) also contribute to the unique biology of them, Yuan and Patrick were Merkel cell carcinoma on the eyelid of an 80-year-old defining illness. The epidemiology of KS pathogenesis of KS. awarded the SGM Marjorie Stephenson patient. Paul Nghiem MD PhD; www.merkelcell.org in HIV-infected people, studied largely Prize in 2012, for which their lecture by Valerie Beral, led many to search for MCPyV at the Spring conference in Dublin was a causal agent that was hypothesised to Undeterred by their considerable entitled ‘Old themes and new variations in be a virus. In 1994, the husband and wife success in discovering KSHV, Yuan human tumour virology’ (a video of this team of Yuan Chang and Patrick Moore and Patrick went on to discover lecture is available on the SGM YouTube used a new technique (representational yet another virus, Merkel cell channel at http://bit.ly/14dcTsv). difference analysis) to identify new polyomavirus (MCPyV), this time by DNA fragments in KS tissue compared a technique they devised called digital Tumour viruses do not to healthy tissue of the same patient. transcriptome subtraction (DTS). This always cause cancer These fragments belonged to a new virus virus is very likely to be the cause of A common theme of human tumour that Yuan and Patrick called Kaposi’s Merkel cell carcinoma, an aggressive viruses is that they are not rare, yet sarcoma-associated herpesvirus (KSHV). cutaneous malignancy that arises from they confer a significant risk for cancer these checkpoints to turn a healthy cell Laura N. Hindle & Fifteen years after its discovery, KSHV neuroendocrine mechanoreceptors development. This begs the question: The future into a malignant transformed cancer cell David J. Blackbourn was formally acknowledged as the causal (Merkel cells) in the basal layer of the why doesn’t everyone infected with such Understanding virus-associated is not a one-step event. Alfred Knudsen University of Birmingham, Cancer Research agent of KS and a rare lymphoma called epidermis. As indicated by its name, viruses develop cancer? First, there are cancer has made an important hypothesised in 1971 that one cancer UK Institute for Cancer Studies, Edgbaston, primary effusion lymphoma. Of the MCPyV belongs to the Polyomaviridae checkpoints built into the mechanism impact on improving human health. in particular, childhood retinoblastoma, Birmingham B15 2TT; Email [email protected]; 84 genes encoded by KSHV, a subset family, members of which have a strong controlling cell division, and overcoming The implementation of an HBV could evolve in as few as two steps. In vaccine dramatically reduced infection [email protected] general it is recognised that multiple with this virus, and concomitantly Kaposi’s sarcoma skin Further reading (perhaps 4–6) steps need to be overcome HBV-associated HCC. plaques on the skin of www.nobelprize.org/nobel_prizes/medicine/ an AIDS patient. National in order to generate a transformed cell. Another success is likely to be www.who.int/csr/disease/hepatitis/en/index. Cancer Institute Various factors (host genetics, diet, lifestyle, the efficacy of HPV vaccines in reducing html etc.) contribute to each step. Second, the the human burden of cancer of the de Martel, C. & others (2012). Global burden of immune system plays an important role in cervix. New generation therapeutics cancers attributable to infections in 2008: a review preventing virus-mediated tumorigenesis. inhibiting HCV replication and and synthetic analysis. Lancet Oncol. 13, 607. Since our immune system is highly undergoing clinical trials may likewise Knudson, A.G., Jr (1971). Mutation and cancer: adapted to distinguish self from non-self, reduce the burden of HCC associated statistical study of retinoblastoma. Proc Natl Acad Sci and viruses represent non-self, the immune with this virus. Hopefully these success U S A 68, 820. system can in many cases recognise viral stories will continue. Mesri, E.A., Cesarman, E. & Boshoff, C. proteins expressed in transformed cells and But what’s next? Are there other (2010). Kaposi’s sarcoma and its associated herpesvirus. Nat Rev Cancer 10, 707. eliminate those cells. When the immune human viruses yet to be discovered that Moore, P.S. & Chang, Y. (2010). Why do viruses system is compromised, surveillance is can therefore be targeted to provide hope cause cancer? Highlights of the first century of reduced and the risk of cancer is in the treatment and prevention of their human tumour virology. Nat Rev Cancer 10, 878. increased. Thus, cancer development respective tumours? With current and Mukherjee, S. (2011). The Emperor of all Maladies: is multistep and multifactorial. Tumour rapidly developing molecular tools, we A Biography of Cancer. London: HarperCollins. viruses can contribute one of the steps may not need to wait too long to find Rott, R. & Siddell, S. (1998). One hundred years in the pathway. out. of animal virology. J Gen Virol 79, 2871.

20 Microbiology Today Feb 2013 Microbiology Today Feb 2013 21 Using global data on cancer the underlying causal infections; indeed just for identifying levels of disease, specific criteria for data quality and Collectively, infections incidence and mortality from 2008, in parts of sub-Saharan Africa, the prioritising health service activity and completeness) population-based cancer it was estimated that there were 12.7 proportion is more than a third of all monitoring success of cancer control registries in the world. However, there are the most important million new cancer cases that year and cancer cases. Among women, carcinoma initiatives, but also because understanding is significant geographic variation in the 7.6 million deaths; about two-thirds of of the uterine cervix is by far the most patterns of disease occurrence underpins availability of such data – whilst the most established cause of cancer cancer deaths occurred in less-developed common infection-associated cancer epidemiology and can provide insights recent volume of CI5 covers about 83% countries. Of those cancer cases, about (about 50% of the total) and, in men, into aetiology. For example, Denis of the population of North America, 6, after tobacco. What are the 16% (approximately 2 million cases) liver and gastric cancers account for about Burkitt’s careful mapping of the 4 and 1% of the populations of South were estimated to be attributable to 80% of the total. Those cancers that are distribution of the tumour that now America, Asia and Africa, respectively, prospects for prevention of infections (viruses, macro-parasites and attributable, at least in part, to underlying bears his name led him to postulate an are covered by such registries. Taking a bacterium). About 1.9 million cases infections are shown in Table 1. underlying infectious cause, ultimately Africa as an example, out of 53 countries, infection-associated cancers, were caused by human papillomaviruses Estimating the burden and leading to the discovery of the first only five have cancer registries of (HPVs), hepatitis B and C viruses (HBV geographical distribution of cancer and human oncogenic virus – the Epstein– sufficient quality to be included in the and what challenges does and HCV) and the gastric bacterium specifically of infection-associated cancer Barr Virus (EBV). latest volume of CI5 – Algeria, Egypt, Helicobacter pylori. The proportion of is far from straightforward. Cancer The series Cancer Incidence in Five Tunisia, Uganda and Zimbabwe (http:// the research community cancers caused by infection tends to be incidence is defined as the frequency Continents (CI5), first published in 1962 globocan.iarc.fr). In addition, there are higher in less-developed than in developed of new cases of cancer in a defined and soon to emerge in its 10th volume, around 50 local registries (which do not regions (approximately 23 versus 7%), population over a specific time period compiles and presents incidence data meet the stringent inclusion criteria for face? reflecting the background prevalence of and accurate data are important, not from the best (as defined by highly CI5) covering a further 7% of the African population, although these predominantly encompass urban rather than rural areas. In such countries, cancer registration is bedevilled by three related problems: (i) Cancers inadequate characterisation of disease – histological verification of diagnosis is typically only available for a proportion of cases; (ii) incomplete ascertainment of cases, particularly at older ages; and (iii) attributable to inadequate ascertainment of population denominator data (from a census). Therefore, any assessment of the burden of cancer – and within that, the burden just of those cancers caused by infections infection – the – is complex and potentially inaccurate. In addition to the problems of measuring the burden of specific cancers highlighted above, there are other concerns associated with estimating the global burden proportion of each cancer type caused by specific infections (the Population Attributable Fraction). It requires the best available evidence on the causal effect of each infection together with an robert newton accurate estimate of the prevalence of iStockphoto / Thinkstock

22 Microbiology Today Feb 2013 Microbiology Today Feb 2013 23 Understanding the role” of infections as a cause of cancer is important, since many infection-associated tumours are avoidable.” Table 1. Cancers caused – at least in part – by infectious agents infection among cases (which may vary by features of Kaposi’s sarcoma – again and, more recently, by widespread use Further reading geographic region). Inevitably, the estimates highlighted by Beral and others – of anti-retroviral drugs, which reduce Beral, V. (1974). Cancer of the cervix: a sexually rely both on the quality of source data prompted a search for the underlying transmission of infection at a population transmitted infection? Lancet 1, 1037–1040. Beral, V., Peterman, T.A., Berkelman, R.L. Infectious agent(s) Cancers and, where data are few, on the statistical infectious cause, subsequently identified level. Perinatal transmission of HTLV-1 methods used to overcome these problems. by Chang & Moore in 1994. More has been greatly reduced in Japan by & Jaffe, H.W. (1990). Kaposi’s sarcoma among Epstein–Barr virus Nasopharyngeal carcinoma, Burkitt’s lymphoma, persons with AIDS: a sexually transmitted infection? For example, human papillomavirus recently, the association between human avoidance of prolonged breast-feeding, post-transplant lymphoproliferative Lancet 35, 123–128. (HPV) is considered to be a necessary immunodeficiency virus (HIV)-related although this is not an option for many disease, extra-nodal NK/T-cell lymphoma, Bouvard, V., Baan, R., Straif, K. & others Hodgkin lymphoma, gastric carcinoma, cause of cancer of the cervix and Kaposi’s immune suppression and Merkel cell developing countries, where alternatives (2009). A review of human carcinogens – Part B: lympho-epithelioma-like carcinoma sarcoma-associated herpesvirus (KSHV) carcinoma prompted the discovery of may not be available and where the risk Biological Agents. Lancet Oncol 10, 321–322. of Kaposi’s sarcoma, but EBV or human Merkel cell polyomavirus (MCV), again of death from diarrhoeal disease rises Bouvard, V., Baan, R., Grosse, Y. & others Hepatitis B virus Hepatocellular carcinoma, cholangiocarcinoma, T-cell leukaemia virus type 1 (HTLV-1) by Chang & Moore. Indeed, throughout markedly if breast-feeding is curtailed. H. (2012). Carcinogenicity of malaria and of some non-Hodgkin lymphoma cause only a proportion of lymphomas the history of infections and cancer, it pylori is a treatable infection and indeed polyomaviruses. Lancet Oncol 13, 339–340. Hepatitis C virus Hepatocellular carcinoma, cholangiocarcinoma, and leukaemias. Nor do these estimates is the multi-disciplinary combination prevalence of infection – and incidence Burkitt, D. (1962). A children’s cancer dependent non-Hodgkin lymphoma take into account the impact of multiple of epidemiology and virology that has of stomach cancer – has been falling in on climatic factors. Nature 194, 232–234. Chang, Y., Cesarman, E., Pessin, M.S. & Kaposi’s sarcoma-associated Kaposi’s sarcoma, primary effusion lymphoma, infections on cancer risk, such as the proved highly successful in uncovering the many populations for years. The value others (1994). Identification of herpesvirus-like herpesvirus multicentric Castleman’s disease of large-scale eradication trials, however, combined effects of EBV and malaria on causes of a range of malignancies. DNA sequences in AIDS-associated Kaposi’s Human immunodeficiency virus Kaposi’s sarcoma, non-Hodgkin lymphoma, the risk of Burkitt’s lymphoma. Understanding the role of infections remains uncertain. sarcoma. Science 266, 1865–1869. type 1 Hodgkin lymphoma, carcinomas of the cervix, One further problem, of course, as a cause of cancer is important, So, the prospects for prevention of Chang, M.H., You, S.L., Chen, C.J. & others anus and conjunctiva (possibly also the vulva, is that there may be other cancer sites since many infection-associated infection-associated cancers are good, (2009). Decreased incidence of hepatocellular vagina, penis and liver) [note: HIV-2 has been or types, not listed in Table 1, that tumours are avoidable. For example, although it may be decades before the carcinoma in hepatitis B vaccines: a 20-year follow- associated with Kaposi’s sarcoma and non- have an underlying infectious aetiology malignancies caused by HPV and HBV impact of prevention programmes are up study. J Natl Cancer Inst 101, 1348–1355. Hodgkin lymphoma] yet to be discovered. For example, the are preventable by vaccination. Most manifest in the general population. It de Martel, C., Ferlay, J., Franceschi, S. substantial excess risk of cutaneous notably, in Taiwan, the incidence of also seems likely that further discoveries & others (2012). Global burden of cancers Human papillomavirus type 16 Carcinomas of the cervix, vulva, vagina, penis, attributable to infections in 2008: a review and squamous cell carcinoma among hepatocellular carcinoma has fallen will be made, linking known or novel anus, oral cavity, oropharynx, larynx and tonsils synthetic analysis. Lancet Oncol 13, 607–615. immune-suppressed individuals has markedly since the introduction of infections to additional cancer sites or [note: HPVs 18, 31, 33, 35, 45, 52, 58 and to Doll, R., Payne, P. & Waterhouse, J., eds (1966). a lesser extent, 39, 51, 56, 59, have also been led many to suspect an underlying vaccination against HBV, coupled with types. Finally, the growing importance Cancer Incidence in Five Continents: a Technical Report. associated with cancer of the cervix in particular] infectious aetiology – certain cutaneous the provision of immunoglobulin at birth of co-infection as a risk factor for certain International Union against Cancer. Springer. HPV types have been investigated, but to prevent vertical transmission. Similarly, cancers is becoming better recognised Human T-cell leukaemia virus Adult T cell leukaemia/lymphoma Durst, M., Gissmann, L., Ikenberg, H. & zur evidence remains scant. Historically, such vaccines against HPV have shown nearly and presents fresh challenges to the Hausen, H. (1983). A papillomavirus DNA from type 1 epidemiological clues have provided the 100% efficacy in preventing HPV-16 and research community. a cervical carcinoma and its prevalence in cancer Merkel cell polyomavirus Merkel cell carcinoma evidence required to prompt a search -18-induced precancerous lesions of the biopsy samples from different geographic regions. Robert Newton Helicobacter pylori Non-cardia gastric carcinoma, gastric B-cell for an underlying infectious cause of cervix. No vaccine is yet commercially Proc Natl Acad Sci U S A 80, 3812–3815. Senior Clinical Epidemiologist at the MRC/UVRI lymphoma of mucosa-associated lymphoid tissue cancer. The extraordinary geographic available for any other cancer-causing Feng, H., Shuda, M., Chang, Y. & Moore, P.S. Research Unit on AIDS, PO Box 49, Entebbe, (2008). Clonal integration of a polyomavirus in Clonorchis sinensis Cholangiocarcinoma variation in the incidence of Burkitt’s infection, but for HCV, iatrogenic Uganda; Reader in Clinical Epidemiology at the human Merkel cell carcinoma. Science 319, 1096–1100. Opisthorchis viverrini Cholangiocarcinoma lymphoma and its association with the transmission can be avoided with safer University of York; and Senior Visiting Scientist at Ferlay, J., Shin, H.R., Bray, F., Forman, D., Schistosoma haematobium Urinary bladder cancer [note: Schistosoma distribution of holo-endemic malaria is a injection and transfusion practices. This the International Agency for Research on Cancer, Mathers, C. & Parkin, D.M. (2010). Estimates japonicum has also been linked with colorectal and classic example. Take too, the association is true for some HIV infections, which Lyon, France; Email [email protected] of the worldwide burden of cancer in 2008: liver cancers] of cancer of the cervix with sexual can also be avoided via behaviour change or [email protected] GLOBOCAN 2008. Int J Cancer 127, 2893–2917. behaviour, highlighted in a seminal paper Malaria Burkitt’s lymphoma by Beral in 1974 (and followed by others), For most of the associations shown, the evidence has been considered robust enough that the which led to the identification of the International Agency for Research on Cancer (IARC) have classified the infections as being Group sexually transmitted infection HPV-16 1 carcinogens (definitely carcinogenic to humans). For Merkel cell polyomavirus and malaria, the by zur Hausen and colleagues in 1983. classification is Group 2A (probably carcinogenic to humans). Similarly, the distinctive epidemiological

24 Microbiology Today Feb 2013 Microbiology Today Feb 2013 25 is the most frequent type found in cervical Thus, through deregulation of two high-risk infections therefore have an Jo parish & adenocarcinomas. major tumour suppressor pathways (Rb increased risk of the emergence of and p53), the viral oncoproteins create immortal cells, which have a better growth HPV-INDUCED CARCINOGENESIS an environment that is beneficial for virus advantage than surrounding cells, and sally roberts What is it about the high-risk viruses that replication in the differentiating cell of an increased risk of acquiring oncogenic differentiates their pathogenesis from that the infected epithelium. However, since mutations leading to malignancy. of the vast majority of HPVs? This was the p53 pathway has a critical role in Another characteristic of high-risk largely answered when the functions of sensing genomic damage and instigating HPV types relevant to their oncogenic the viral proteins E6 and E7 of high-risk its repair, the high-risk viruses, through nature is the tendency of their genomes viruses were compared with those of the deregulation of p53 signalling have to integrate into the host DNA. The site non-cancer-causing viruses. These two created an environment that promotes of breakage within the viral genome HPV proteins act in a cooperative fashion genetic instability of cellular DNA that is preferentially restricted to a region to promote cell proliferation so the virus subsequently goes unchecked. Persistent encoding the viral transcriptional Human papillomaviruses

Human papillomaviruses (HPV) can utilise the host’s DNA replication Warts on the skin caused by human are small, double-stranded DNA viruses machinery, and to ensure cell survival such papillomavirus (HPV) may be relatively that infect epithelial tissue, such as skin and that the virus replicates before the cell the ‘wet’ mucosal epithelial linings of the dies. The E6 and E7 proteins of high-risk harmless, but a few of the nearly 120 anogenital tract and oropharynx, generally viruses have evolved different strategies to inducing warts and papillomas. To date, accomplish these functions. strains of HPV identified to date have nearly 120 distinct genotypes of HPV The key role of the high-risk E7 far more serious consequences. What have been identified and whilst infections oncoprotein is to induce hyperproliferation caused by the majority of these types are of host cells by targeting multiple processes mechanism do they use to induce not a clinical burden, a small number have controlling cell-cycle regulation. This been shown to induce disease of significant includes the retinoblastoma (Rb) family of cancer and what can be done about it? clinical relevance. Some types are linked tumour suppressors that regulate entry into to the development of non-melanoma S phase, where DNA synthesis occurs. By skin cancers, and some, such as HPV-6 binding to Rb and inducing its degradation, and HPV-11, are the primary cause of E7 induces the release of the E2F family genital warts. A subset of 13 HPV types is of transcription factors that activate the associated with the development of cancers expression of genes necessary for S phase of the anogenital tract (cervix, vulva, vagina, entry. The host response to unscheduled penis and anus) and of the head and neck activation of the cell’s replication machinery (tonsil, base of tongue and oropharynx). is the induction of apoptosis. This is False-colour transmission electron Even within this group of ‘high-risk’ viruses, counteracted by the E6 oncoprotein that has micrograph of HPV particles. CNRI / some types are more prevalent than others; evolved several strategies to block this cell Science Photo Library HPV-16 is most commonly associated with signal, including the targeted degradation squamous cell carcinoma of the cervix and of the main executioner of this response, head and neck carcinomas, whilst HPV-18 the tumour suppressor protein p53.

26 Microbiology Today Feb 2013 Microbiology Today Feb 2013 27 ”The development of HPV-associated cancer is a late and rare complication of Light micrograph of HPV-infected cells from a cervical smear showing typical clear cytoplasm and enlarged nuclei persistent infection by (purple). Biomedical Imaging Unit, Southampton General Hospital / Science Photo Library high-risk HPV types and is the end game of a chain and reduced recurrence rates, but acute and severe local inflammation can be problematic. of events that unfold over Maintenance of the malignant phenotype absolutely requires the many years. expression of E6 and E7 oncoproteins. ” Targeting these proteins to treat HPV- regulator, E2. The consequence of cause of cervical cancer, it was hoped that vaccine which confers resistance to induced disease is therefore an appropriate integration is therefore the severance of the detection of HPV DNA sequences in HPV-16, -18, -6 and -11 is now in use. strategy. Trials of therapeutic HPV the negative feedback signal mediated by cervical smears could be used to improve Trials with both of these vaccines have vaccines composed of E6 and E7 peptides E2 upon the expression of E6 and E7, the effectiveness and efficiency of cervical shown significant protection against in various forms have shown efficacy in resulting in unchecked expression of these screening. Towards this end, the NHS HPV-16- and HPV-18-related carcinomas the clinical regression of benign and pre- two oncoproteins. is trialling a new protocol for cervical and, in addition, Gardasil has an efficacy cancerous lesions, but a successful outcome The development of HPV-associated screening in which women found to of almost 90% against genital warts. is not so obvious in patients with high- cancer is a late and rare complication of have borderline or mild dyskaryosis are The antigens in both vaccines are grade cancer. persistent infection by high-risk HPV types routinely tested for HPV sequences. Those virus-like particles (VLPs) composed In addition to the development of and is the end game of a chain of events women that are positive for high-risk of the L1 major capsid protein. Due therapeutics useful in treating HPV- that unfold over many years. However, HPV will be sent directly for microscopic to conformational changes that are associated disease, work is on-going infection by these viruses is necessary examination of the cervix (colposcopy), required at the surface of HPV virions to develop antiviral compounds. The for the initiation and maintenance of instead of cytological surveillance every during virus entry into the host cell, virus inhibition of HPV DNA replication the cancer phenotype and the virus is 6 months. Women who are negative, entry takes several hours. The presence by chemical inhibition of the viral E1 therefore an important target for antiviral however, will be returned for routine of VLP-induced antibodies prevents helicase is one such strategy and, while intervention and therapeutic treatments. surveillance every 3–5 years. This new attachment of the virus to the basement potent molecules have been developed in screening protocol will reduce the rate of membrane underlying the epithelia vitro, these compounds are not effective in COMBATING HPV-INDUCED repeat smears, but increase the number of and entry into host cells. This means vivo. Similarly, the potential to block DNA DISEASE women referred for colposcopy. that while Gardasil and Cervarix are binding of E1 or the viral replication/ To combat HPV-induced disease, clinicians Notwithstanding the extraordinary extremely effective for prophylactic use, transcriptional regulator protein E2 has and researchers have developed an arsenal progress that has been made towards the individuals that already have a persistent been explored, with only a handful of of prophylactic and therapeutic strategies. diagnosis and treatment of cervical and HPV infection cannot benefit from compounds showing activity in vivo. Nonetheless, HPV-associated disease is still other anogenital malignancies in more vaccination. It is for this reason that the Undoubtedly, the development significant, particularly in the developing developed countries, HPV-associated vaccine is specifically targeted to young of prophylactic vaccines has been an regions of the world, where high-risk cancers continue to be an important girls before they have reached their sexual important step in our effort to control HPV infections and the consequent source of morbidity and mortality. In debut. The prevention and treatment of HPV infection. However, it is clear that the cancers are rarely diagnosed or treated; 2010, there were over 6,500 new cases of HPV-associated disease in unvaccinated incidence of some HPV-associated cancers cervical cancer remains the most common HPV-associated cancers diagnosed and individuals therefore remains a priority. is increasing and, along with high levels of cancer in women worldwide, especially in over 2,000 deaths from these cancers in At present, therapies for anogenital HPV HPV-associated cancers in the developing sub-Saharan Africa. Moreover, in these England alone. infections are limited. Surgical ablation, regions of the world, the race to prevent parts of the world the recently developed In the UK, since 2008 there has been which is effective in the short-term but and treat HPV infection is far from over. prophylactic vaccines are not widely a national programme for the vaccination associated with high recurrence rates, and available for financial and logistical reasons. of girls aged 12 to 13 using a bivalent cytotoxic agents, such as trichloracetic Jo Parish & Sally Roberts The introduction of cervical screening vaccine called Cervarix, which targets acid and podophyllotoxin, are common School of Cancer Sciences, Cancer Research in 1964 in the UK has been followed by HPV-16 and HPV-18 that together cause in the treatment of genital warts, but have UK Cancer Centre, University of Birmingham, substantial reductions in mortality caused 70% of cervical carcinomas. In 2012, the issues with patient tolerance. Immune Edgbaston, Birmingham B15 2TT; Tel. +44 (0)121 An adolescent girl receiving a cervical by cervical cancer. When it was realised NHS announced a change in the HPV modulators, such as Imiquimod, applied 414 7459; Email [email protected], s.roberts@ cancer vaccine. May / Science Photo Library that HPV was a necessary and sufficient vaccine used. Gardasil, a quadrivalent topically to genital warts have high efficacy bham.ac.uk

28 Microbiology Today Feb 2013 Microbiology Today Feb 2013 29 Jane A. McKeating & Colin R. Howard

marked increase in the incidence of hepatitis C virus (HCV)-associated HCC, an RNA virus closely related to Viral the flaviviruses. The liver undergoes rapid regeneration following destruction of hepatocytes, maximising the opportunities for the development of hepatitis and chromosomal abnormalities leading to HCC. The observation that HBV and HCV, two viruses with such widely differing replication strategies, are the major agents predisposing the human hepatocellular liver to cirrhosis and hepatoma suggests an indirect role for infection in the carcinogenic process. Abnormalities arising from prolonged infection with either virus are most likely exacerbated by carcinoma environmental factors, such as aflatoxin, alcohol abuse or the release of superoxides and free radicals associated with chronic inflammation.

HBV The evidence for a causal relationship between HBV infection and HCC is need to increase our understanding What Primary liver cancer, or overwhelming. Active HBV infection of the mechanisms underlying HCC hepatocellular carcinoma (HCC), is the and HCC share a common geographic pathogenesis to provide new targets for strategies most common liver malignancy with distribution and most HCC cases arise in therapeutic intervention and vaccination. an estimated 750,000 new cases and HBV carriers. A landmark prospective Hepatitis B virus (HBV), a DNA can we use to 695,000 deaths per year, rating third in study of 22,000 individuals in Taiwan virus in the family Hepadnaviridae, has incidence and mortality in the world. showed that men positive for HBV been implicated in the development of tackle virus- Whilst the majority of cases occur in the had over 200 times the rate of HCC, HCC. Depending on the geographic Far East and Sub-Saharan Africa, HCC compared to a similar, uninfected cohort. area, more than 50% of HCC cases are induced liver diagnosis is increasing in Europe. Recent HBV infection may lead indirectly to attributed to HBV and infected subjects Cancer Research UK figures project a hepatoma development following chronic have an approximate 100-fold increase cancer, a 40% increase in HCC in the UK between liver injury, due to immune attack on in the relative risk of developing HCC 2010 and 2030. Whilst incidence and virus-infected hepatocytes. Chronic liver compared to uninfected patients. By serious and mortality for other common cancers regeneration predisposes to tumour comparison, smoking increases the risk are declining, this cancer represents development. This concept is supported of cancer tenfold. In contrast, where increasing an increasing public health problem. by the fact that alcoholic cirrhosis HBV prevalence is low, such as the USA, HCC is a complex and heterogeneous predisposes to HCC. public health tumour with limited treatment options Europe and Japan, chronic hepatitis B is Woodchucks (Marmota monax) infected Molecular model of the hepatitis B virus and poor prognosis due to recurrence associated with fewer than 20% of HCC with the woodchuck hepatitis B virus capsid. Laguna Design / Science Photo Library problem? and metastases. Hence, there is a real cases. These countries have witnessed a

30 Microbiology Today Feb 2013 Microbiology Today Feb 2013 31 The introduction Coloured scanning electron micrograph ” of an HCC cell of HBV vaccines into undergoing mitosis. Steve Gschmeissner / childhood immunisation Science Photo Library programmes over the next two decades will lead to a marked reduction in HCC in countries where the virus is endemic.

(WHBV) have provided a valuable” surface glycoproteins, or truncated MicroRNAs (miRNAs) are those individuals at risk of developing model to study the role of HBV in products, may also participate in increasingly a focus of interest HCC: the introduction of HBV HCC pathogenesis, with the majority of carcinogenesis but none of the seven in the role of HBV or HCV in vaccines into childhood immunisation animals infected as neonates developing HBV polypeptides appear to act as hepatocarcinogenesis. HCV replication programmes over the next two decades liver cancer by 3 to 4 years of age. dominant oncogenes. is dependent upon miR-122, a liver- will lead to a marked reduction in HCC Activation of the N-myc oncogene has specific miRNA that plays a key role in in countries where the virus is endemic. been associated with the integration of HCV tumour suppression, and HBV has been It is to be hoped that a similar strategy WHBV DNA in over 90% of tumours; Over 75% of individuals parenterally shown to alter the expression profiles of could prove equally as effective to reduce however, this insertional activation of a exposed to HCV develop a persistent this and other miRNAs. But how these the burden of HCV infection and thus common oncogene has not been found infection and, among this cohort, up to altered profiles predispose hepatocytes effectively eliminate virus-induced liver in human HCC. 5% develop HCC later in life. Although to cellular transformation remains to be cancer in years to come. Tumours are usually clonal with this percentage is small, globally this elucidated. respect to the integrated viral sequences, represents around 9 to 10 million cases at Jane A. McKeating & suggesting that integration occurs any one time. HCV causes chronic liver Conclusion Colin R. Howard prior to the expansion of tumour cells, injury that can progress to severe fibrosis Most HBV chronic infections are School of Immunity and Infection, College of many years prior to the development and cirrhosis. HCV is a positive-stranded acquired in the first few months of life Medical and Dental Sciences, Medical School of cancer. The hepadnavirus genome RNA flavivirus that replicates in the and such long-term carriers are at high Building, University of Birmingham, Edgbaston, does not contain a known oncogene: cytoplasm and does not integrate into the risk of developing HCC in adulthood. Birmingham B15 2TT; Tel. +44 (0)121 414 8173; cellular enzymes such as topoisomerase host genome, supporting the hypothesis For this reason, it is recommended Email [email protected] I are thought to be responsible for that hepatocellular carcinogenesis occurs that infants in regions of high HBV Further reading recombination, which is not restricted via indirect effect(s) of infection on prevalence are vaccinated at or shortly Bouchard, M.J. & Navas-Martin, S. (2011). to any specific region of the host chronic inflammation and hepatocyte after birth. Vaccination against HBV has Hepatitis B and C virus hepatocarcinogenesis: chromosome. HBV integration promotes injury. However, inflammation alone proven effective, not only in reducing lessons learned and future challenges. Cancer Lett genetic instability by undergoing repeated is not sufficient to cause HCC since the prevalence of HBV carriage, but in 305, 123–143. mutations, deletions and inversions. The conditions such as autoimmune hepatitis lowering the incidence of HCC later El-Serag, H.B. & Rudolph, K.L. (2007). mammalian hepadnaviruses contain a rarely develop HCC. Several HCV- in life, thus making HBV vaccines the Hepatocellular carcinoma: epidemiology and gene, X, which encodes a trans-activating encoded proteins have been reported to first widely available vaccine against a molecular carcinogenesis. Gastroenterology 132, protein that is absent in the genome of play a role in the development of HCC human cancer. 2557–2576. non-oncogenic avian hepadnaviruses; in experimental and transgenic animal Antivirals are increasingly effective Lemon, S.M. & McGivern, D.R. (2012). Is however, conclusive evidence that the systems. However, many of these reports for the treatment of chronic HBV and hepatitis C virus carcinogenic? Gastroenterology 142, X gene is a mediator of hepatocyte have studied HCV proteins expressed HCV infection and, although their 1274–1278. oncogenesis is lacking. It has been noted in isolation, raising questions on the use may retard the development of Lok, A. (2011). Does antiviral therapy for hepatitis B and C prevent hepatocellular that X may be required for the early physiological relevance of the model cirrhosis and HCC, there is no definitive carcinoma? J Gastroenterol Hepatol 26, 221–227. stages of oncogenesis, but not for later systems. Recent advances allowing the evidence that their application can stages, since HBV gene expression is close assembly of infectious HCV particles prevent the development of HCC unless to zero in HCC tumours. Unregulated X in vitro will enable studies to investigate administered early after infection and expression is associated with hepatocyte the effect(s) of virus replication on host virus infection is resolved. In both cases, carcinogenesis in transgenic mice. The cellular pathways involved in oncogenesis. surveillance is key in order to identify

32 Microbiology Today Feb 2013 Microbiology Today Feb 2013 33 Epstein–Barr virus: opportunities for prophylactic and therapeutic vaccines James E. Turner & Graham S. Taylor

Epstein–Barr virus is now known to be associated with several forms of cancer, in addition to its potential to cause glandular fever. Are vaccines the answer to conquer this ubiquitous virus?

The burden of EBV- able to control their EBV infection, associated diseases the virus nevertheless establishes a Given that it infects over 90% of lifelong infection of B cells hidden from people worldwide, Epstein–Barr Virus the immune system. Periodically, the (EBV) is a highly successful pathogen. virus reactivates in some of these cells We have co-evolved with this virus over to complete its life cycle, producing new millions of years, achieving a state of viruses that are spread to other people détente. EBV infection during childhood, via saliva. which until recently was the normal However, since its discovery in state of affairs, usually passes unnoticed. 1964 in Burkitt’s lymphoma cells, several Improvements in living standards mean other cancers have been linked to EBV. that, increasingly, infection is delayed In terms of morbidity and mortality until adolescence or later, whereupon two cancers stand out. Nasopharyngeal EBV infection can cause infectious carcinoma (NPC) is rare in most Western mononucleosis (glandular fever) with countries but prevalent throughout South symptoms of fever, sore throat, swollen East Asia. Some 75,000 cases occur each lymph nodes and a debilitating fatigue year, of which almost all are positive for that can persist for months. While most EBV. More recently, EBV has been found people mount a strong immune response in almost 10% of gastric carcinoma Coloured transmission electron micrograph of EBV particles (red) in the nucleus of a malignant white blood cell. Steve Gschmeissner / Science Photo Library

34 Microbiology Today Feb 2013 Microbiology Today Feb 2013 35 Coloured transmission electron micrograph of an EBV particle. James Cavallini / Science Photo Library

Even if the perfect prophylactic EBV vaccine people are protected against acquiring EBV immune responses that usually way that can be applied to large numbers ” additional EBV strains following their prevent virus-infected cells from growing of patients worldwide. To achieve this became available tomorrow, millions of people initial infection. Evidence of such natural out of control. Consequently, restoring goal, our research group has developed protection following EBV infection these immune responses by infusing a genetically engineered vaccine based already infected with the virus will go on to develop would be a strong stimulus for developing EBV-specific immune cells grown in the on Modified Vaccinia Ankara (MVA), a second-generation prophylactic EBV laboratory often results in the elimination safe attenuated strain of poxvirus. Into virus-associated cancers. vaccines. of the cancer. MVA we introduced the genes for the two ” Post-transplant lymphoma does, EBV proteins that are present in almost tumours. Although the proportion of offer some benefit, for example by Therapeutic vaccines however, represent a somewhat idealised all EBV-positive cancers. This vaccine virus-positive gastric carcinomas is much reducing the incidence or severity of to treat EBV-associated situation for such immunotherapy has recently completed testing in two lower than NPC, there are far more cases infectious mononucleosis in uninfected cancers because the cancer cells contain at least early-phase clinical trials performed in of this disease worldwide (an estimated 1 adolescents, the need for an effective Even if the perfect prophylactic EBV eight EBV proteins and some of these collaboration with Cancer Research UK million cases per year). This means that prophylactic vaccine remains. vaccine became available tomorrow, are good immune targets. In contrast, and colleagues in Hong Kong, London, the number of virus-positive cases of Since the gp350 vaccine alone could millions of people already infected all other EBV-associated cancers Manchester and Birmingham. The results these two cancers is actually very similar. not protect against EBV infection, a truly with the virus will go on to develop contain fewer viral proteins that are of these trials show that the vaccine can EBV is also associated with several preventative vaccine is likely to need virus-associated cancers. Irrespective of poorer targets for the immune system. boost immune responses to one or both different lymphomas, the most common additional antibodies targeting other progress towards a prophylactic vaccine, This is presumably because these other of the EBV proteins when administered being Hodgkin lymphoma. In total, virus proteins, as well as perhaps also the desperate need for better treatments cancers have developed in individuals to NPC patients and, equally importantly, almost 200,000 cases of EBV-associated enlisting the T cell arm of the immune for EBV-positive NPC, gastric carcinoma with relatively ‘normal’ immunity. is well-tolerated with relatively minor side cancer occur each year worldwide. system. Ideally, this would be achieved and lymphoma remains. One way this Nevertheless, several clinical trials have effects. The vaccine is now being tested using a live but attenuated vaccine strain could be achieved is by making use of shown that infusing EBV-specific immune in two new much larger clinical trials that Prophylactic vaccines to of EBV. However, the fact that EBV is the fact that all EBV-associated cancers cells into patients with EBV-positive will measure the ability of the vaccine to prevent EBV infection associated with cancer development raises express one or more EBV proteins. It Hodgkin lymphoma or NPC can result shrink, or even eliminate, EBV-associated Prophylactic or preventative vaccines enormous, probably insurmountable, should therefore be possible to eliminate in clinical benefit. These trials serve as tumours. have been successfully developed for regulatory issues for such a vaccine. these cancers by harnessing relevant very important proofs of principle, but several viruses including two human One possible alternative therefore could antiviral immune responses. This has producing the immune cells requires Conclusion tumour viruses (hepatitis B virus and be to use a vaccine comprised of EBV clearly proved to be the case for post highly specialised facilities and staff; EBV is a fascinating virus and its human papillomavirus). Given the virus-like particles. Since these particles transplant lymphoma, an EBV-associated consequently, the cost per patient is study has revealed novel aspects of the burden of EBV-related disease in terms lack virus genetic material, the risk of the cancer that can occur in patients who are high. The challenge now is therefore interaction between viruses, the immune of cancer, but also the debilitating effects vaccine causing cancer is removed while immunosuppressed following organ or to develop ways to focus the immune system and cancer. The results of many of infectious mononucleosis, a similar the presence of multiple viral proteins, stem cell transplantation. These tumours response against the smaller number of years of basic research have already vaccine to prevent EBV infection would displayed in a particulate form, broadens result from the loss of the normal anti- viral proteins present in these cancers in a been translated into the clinic and efforts have a substantial health and economic and enhances the antiviral immune by several research groups worldwide impact. Most vaccine efforts to date have response. However, the key question continue to develop and refine exciting focused on a single EBV protein, called of whether a strong immune response new therapies that will benefit human gp350, because antibodies to this protein The challenge now is therefore to develop ways against EBV can protect against infection health. brought about by natural virus infection remains unanswered. Our research group ” are also able to inhibit virus infection to focus the immune response against the smaller is addressing this fundamental question James E. Turner & of cells in the laboratory. A clinical trial in collaboration with Professor Paul number of viral proteins present in these cancers Graham S. Taylor performed in EBV-uninfected young Kellam’s research group at the Wellcome School of Cancer Sciences, University of adults showed that a vaccine consisting Trust Sanger Institute in Cambridge. in a way that can be applied to large numbers of Birmingham, Vincent Drive, Birmingham of purified gp350 protein reduced the Since different EBV strains circulate in B15 2TT; Tel. +44 (0)121 414 7983; Email incidence of infectious mononucleosis, the population, and each strain can be patients worldwide. [email protected] but was unable to protect against virus identified by its own genetic signature, ” infection. While such a vaccine could we are using deep sequencing to see if

36 Microbiology Today Feb 2013 Microbiology Today Feb 2013 37 schoolZone

Bacteriophage practical

Aspects of virology feature in Aim Stage 2 – Inoculating cultures of bacteria with T4 Results To calculate the number of viable phage in a bacteriophage dilutions The bacteria grow as a lawn (a field of many A-level specifications suspension. The following steps (1–6) must be completed for each dilution confluent growth) across the agar. Small circular gaps in the lawn of bacteria are but practical virology is 1. Collect your ‘10–1‘ agar plate and the bacteriophage dilution Method known as plaques. Here, bacteria have bottle labelled ‘10–1‘. been killed by the bacteriophage so are virtually absent in school Note: Aseptic technique should be used throughout this 2. Collect 3 ml of molten soft agar from a water bath (set at 50°C). unable to grow. experiment because of difficulties When opening the soft agar, ensure you are working aseptically Count the number of plaques at (near a Bunsen burner). Stage 1 – Preparing your dilution series of a dilution where there are between in handling the micro- T4 bacteriophage 3. Using a sterile pipette, transfer 0.2 ml (200 μl) 20 and 200 plaques present. This will of E. coli culture into the soft agar bottle/test tube. allow calculation of number of plaque- organisms (both perceived Each group of students requires 10 nutrient agar plates, 4. Using a sterile pipette, transfer 0.2 ml (200 μl) of forming units (PFUs) per ml of original 10 bottles each containing 9 ml sterile distilled water and real). Bacteriophages your phage dilution into the soft agar bottle/test tube. suspension using the formula: and 10 sterile pipettes. E. coli Bacteriophage (viruses that only infect 1. Label one agar plate ‘10–1‘ and the next one ‘10–2‘ dilution 10–1 (number of PFUs) and so on until ‘10–10‘. PFU/ml = bacteria) are relatively easy (dilution x 0.2) 2. Label the sterile water bottles ‘10–1‘, ‘10–2‘ and so to handle and can be used –10 0.2 ml 0.2 ml 1. Enter the number of PFUs into the on until ‘10 ‘. E. coli (200 µl) (200 µl) –1 10 top line of the equation. to illustrate many concepts 3. Transfer 1 ml of bacteriophage suspension into the sterile water bottle labelled ‘10–1‘ and mix well. of virology, such as counting 2. Enter the dilution you chose for your average PFU where the equation 4. Using a sterile pipette (not the one used says ‘dilution’. For example, if you infectious virus particles. previously), transfer 1 ml out of the ‘10–1‘ bottle 3 ml soft agar chose 10–3, enter 0.001, or if you A plaque assay is a technique T4 bacteriophages and place it into the ‘10–2‘ bottle. Replace the lid –7 for detecting viruses. The underlying infecting an E. coli cell. chose 10 , enter 0.0000001. and mix well. 5. Place lid on bottle/test tube. Carefully rotate/roll the bottle principle offered here is a serial dilution Juergen Berger / Science Photo between two fingers in an upright position, to mix the solution (gradually diluting a suspension Library 5. Continue this process (transferring 1 ml from one Notes (do not shake). of bacterial viruses and testing for dilution to the next using a new sterile pipette each – Soft agar is half-strength nutrient –10 –1 infectivity). The outcome should be an time) until you have made the ‘10 ‘ dilution. 6. Carefully pour the inoculated soft agar onto your ‘10 ‘ agar agar. It must be sterilised and be agar plate covered with ‘plaques’ (holes plate. Replace the lid of the agar plate and carefully rotate the molten (kept at 50°C) for students in a field of constant bacterial growth), plate in a circular motion so the soft agar is evenly spread over to use. the underlying agar. Leave the plate for approximately where the virus has infected and killed 1 ml 1 ml 1 ml – The bacteriophage must be able to 10 minutes for the soft agar to set (at room temperature). infect the bacterium you use. They the host bacterium. …1 ml The school-friendly method are highly specific. – Advice on bacteriophage and detailed here offers a step-by-step guide Bacterio- 10–1 10–2 10–3 10–10 Soft agar to carrying out a plaque assay using T4 phage obtaining a culture can be sought bacteriophage and its host, Escherichia from culture suppliers/collections coli. Once all agar plates have been inoculated with soft agar James redfern, Manchester and the agar has set, invert the plates and incubate them at Bacteriophage 9 ml sterile Metropolitan University suspension distilled water 30°C for 24 hours. Empty bottles/test tubes should be sterilised and cleaned before reuse.’

38 Microbiology Today Feb 2013 Microbiology Today Feb 2013 39 Good bugs, bad bugs

Fun Kids is the UK’s only children’s radio station. With a core Given the chance would you like to So, if you like the sound of it then take part in ‘Good bugs, bad bugs – I would definitely encourage you audience of between 4 and 9 years old, it’s not the SGM’s usual another look down the microscope’? to get involved! You get a lot of audience, but when we were invited by Fun Kids to develop a experience on the job and it makes JV Definitely! you love your subject even more series about microbiology, we jumped at the chance. than before. In the series, called Good bugs, bad PH The work wasn’t really difficult PH Yes! The diversity and importance bugs, microbiology is introduced or time-consuming, it was a nice of microbiology to virtually every Good bugs, bad bugs is available to through the characters Benny (the respite from the usual things that aspect of life on the planet is a listen or download on the Fun Kids good bug) and Mal (the bad bug) in academics do… great thing to get across to kids website www.funkidslive.com. If you a fun and engaging way, covering and this was a great way to go are interested in microbiology outreach, areas of microbiology from microbial What did you think of the final about it! or becoming an SGM Expert, get in transmission to sewage treatment, and episodes, were they what you touch with our Education and Outreach food production to algal blooms! We expected? What advice would you give Officer ([email protected]). asked Chair of the Communications to anyone interested in getting PH They were much better than I Committee Joanna Verran (JV) and involved with any aspect of thought they would be. Reading Microbiology Today Editor Paul microbiology outreach? the scripts makes you imagine Hoskisson (PH) if they would help how the characters would sound, with the planning and development PH It was interesting that as a scientist JV If you like talking about but the Fun Kids team have really of the series. Here they let us know you try not to think about micro- microbiology (or indeed any area brought them to life. how they got on. organisms in an anthropomorphic of science!), then it is always good way, yet in this project, that is to think about how you are going Did this project make you think Why did you get involved with exactly what we were trying to do to explain things in a way that is differently about how you this project? in order to get the message across clear and accurate – but it has to communicate? – I found this a particular challenge. also be interesting or people simply JV Seemed like a fun idea! It’s PH It’s interesting how doing won’t listen. It is about engaging, great to think about how to get something like this makes you Which was your favourite episode? not pontificating. Outreach and microbiology out to as many consider all of the ambiguity in any engagement activities demand a different audiences as possible – sentence, especially when trying to JV I love them all! lot of energy and concentration and why not start them young! simplify microbiology for a young for extended periods, but they are audience. PH Not sure I can choose ... Episode 1, also stimulating, rewarding and How did you get on with the work probably as it gives a nice overview exciting, and often enlightening as involved? What was the most challenging part of the breadth of microbiology. well. Always listen to your audiences of this project? if you want them to listen to you! JV Not too badly – once I got focused Benny or Mal? into the programme’s language it JV Making sure that we were Since the show went on air in mid-December, Good bugs, Bad Bugs was enjoyable to think about how consistent with our messages and JV Benny the beneficent! has reached 200,000 listeners, been downloaded 2,165 times, has 156 best to get important points across language across episodes. It was subscribers on iTunes, had 600 entrants to a competition in its name and in a simple, but accurate and of also nice working with Paul and the PH Benny, obviously – I work on the webpages dedicated to it have had over 1,500 page views! course entertaining, way. team at SGM via ‘track changes’! Streptomyces!

40 Microbiology Today Feb 2013 Microbiology Today Feb 2013 41 sGM journals Standing up for Science See what the microbiology community has been reading…

Erica Kintz

Most read articles – Most read articles – JGV Young scientists often forget how uniquely qualified they are to comment and MICROBIOLOGY Steckbeck, J.D., Kuhlmann, A.-S. & Montelaro, R.C. offer their opinions on poorly performed research and suspicious scientific Hartmann, N., Schulz, S., Lorenz, C., (2012). C-terminal tail of human immunodeficiency virus Fraas, S., Hause, G. & Büttner, D. gp41: functionally rich and structurally enigmatic. J Gen claims. The Standing up for Science workshop for early career researchers, held (2012). Characterization of HrpB2 Virol 94, 1–19; doi:10.1099/vir.0.046508-0 on November 16th at the University of Glasgow, sought to remedy that situation. from Xanthomonas campestris pv. Martínez-Guinó, L., vesicatoria identifies protein regions that Ballester, M., Segalés, J. Organised by Sense about Science their loss of control over a story after address issues important to them; it is are essential for type III secretion pilus & Kekarainen, T. (2011). (www.senseaboutscience.org), a giving it to their editors as the major easier and less intimidating to combat formation. Microbiology 158, 1334–1349; Expression profile and doi:10.1099/mic.0.057604-0 charity dedicated to helping the public reasons that errors are made. They problems with a group of like-minded subcellular localization better understand science and equipping made the argument that fewer mistakes individuals than to think you have to Figueira, R. & Holden, D.W. (2012). of Torque teno sus virus them to inquire about research, the would be made if more scientists were face it on your own. Functions of the Salmonella pathogenicity proteins. J Gen Virol 92, island 2 (SPI-2) type III secretion system effectors. Microbiology 158, 2446–2457; doi:10.1099/ workshop was not intended as a training willing to take the time to converse with The day allowed participants 1147–1161; doi:10.1099/mic.0.058115-0 vir.0.033134-0 course on media relations but instead them over the facts in their articles. to learn more about the process of allowed participants to engage in a The day was interspersed with science reporting, from preparing Hermosa, R., Viterbo, A., Chet, I. & Monte, E. (2012). Plant-beneficial Radford, A.D., Chapman, effects of Trichoderma and of its genes. Microbiology 158, 17–25; D., Dixon, L., Chantrey, J., discussion about the process of how group work sessions that allowed the press releases with the University to doi:10.1099/mic.0.052274-0 Darby, A.C. & Hall, N. science is portrayed in the media. participants to come together and reflect how science stories are chosen and (2012). Application of next- This was accomplished by on their responsibilities as researchers researched by journalists. It also generation sequencing technologies in virology. J Gen Virol Most read articles – running several sessions that offered when engaging with the public and provided an opportunity for participants 93, 1853–1868; doi:10.1099/vir.0.043182-0 perspectives from each side of science media, and also explore reasons why to address their concerns over what IJSEM reporting. In the first session, researchers we feel uncomfortable doing so. may go wrong if and when their science Kaur, I., Kaur, C., Khan, F. & Mayilraj, S. Most read articles – JMM gave examples of their experiences Common answers given were a lack becomes a topic of media attention (2012). Flavobacterium rakeshii sp. nov., Sardi, J.C.O., Scorzoni, L., Bernardi, T., Fusco-Almeida, interacting with the media and offered of experience and a fear that no one and offered advice and encouragement isolated from marine sediment, and A.M. & Mendes Giannini, M.J.S. (2013). Candida species: advice on how to make sure your would take our opinions seriously. on how to become more involved with emended description of Flavobacterium beibuense Fu et al. 2011. Int J Syst Evol current epidemiology, pathogenicity, biofilm formation, research is not misrepresented. This These feelings were addressed in the science in the media. Hopefully, the Microbiol 62, 2897–2902; doi:10.1099/ natural antifungal products and new therapeutic options. included being prepared when speaking final session of the day, which provided 50 participants have been inspired to ijs.0.035691-0 J Med Microbiol 62,10–24; doi:10.1099/jmm.0.045054-0 with journalists and being sure you can participants with options on how they overcome their reluctance and act as . Wieme, A., Cleenwerck, I., Van Jarmuda, S., O’Reilly, N., Zaba, R., Jakubowicz, O., explain how your research relates to the could get involved with helping correct champions of good science for the Landschoot, A. & Vandamme, P. (2012). Szkaradkiewicz, A. & Kavanagh, K. (2012). Potential role bigger picture so that audiences can inaccuracies in science reporting and benefit of the general public. Pediococcus lolii DSM 19927T and JCM of Demodex mites and bacteria in the induction of relate to it. Professor Sergio Della Sala establish themselves as someone the 15055T are strains of Pediococcus acidilactici. Int J Syst Evol Microbiol 62, rosacea. J Med Microbiol 61, 1504–1510; doi:10.1099/ of the University of Edinburgh went so public can trust for scientific facts. Erica Kintz 3105–3108; doi:10.1099/ijs.0.046201-0 jmm.0.048090-0 far as to say that if science was being One piece of advice included starting Centre for Immunology and Infection, Hedberg, M.E., Moore, E.R.B., Svensson-Stadler, L., Hörstedt, P., Watkins, R.R., misreported, it was often the fault of small; we were encouraged to contact University of York, Heslington, York Baranov, V., Hernell, O., Wai, S.N., Hammarström, S. & David, M.Z. & the scientist for not taking the necessary local media over their science articles. YO10 5DD; Email [email protected] Hammarström, M.-L. (2012). Lachnoanaerobaculum gen. nov., Salata, R.A. (2012). care in releasing the information! Another was establishing an online a new genus in the Lachnospiraceae: characterization of Current concepts on the This was followed by an presence with science-related blogs SGM supports Standing up for Science Lachnoanaerobaculum umeaense gen. nov., sp. nov., isolated from virulence mechanisms enlightening session with journalists and social media accounts. Finally, we workshops. Society members can the human small intestine, and Lachnoanaerobaculum orale sp. nov., of meticillin-resistant offering their perspective on why learned more about the Voice of Young apply for a priority place as well as isolated from saliva, and reclassification of Eubacterium saburreum Staphylococcus aureus. occasionally science reporting goes Science network, also run by Sense assistance with travel and subsistence (Prévot 1966) Holdeman and Moore 1970 as Lachnoanaerobaculum J Med Microbiol awry. They listed hectic days covering about Science. This programme helps by contacting [email protected] saburreum comb. nov. Int J Syst Evol Microbiol 62, 2685–2690; 61, 1179–1193; doi: 10.1099/jmm.0.043513-0 multiple stories, limited time frames and early-career researchers connect and doi:10.1099/ijs.0.033613-0 Data accessed 22 Jan 2013

42 Microbiology Today Feb 2013 Microbiology Today Feb 2013 43 “Advanced planning Professional development for early-career is key to success. Last researchers: how to organise a conference minute changes are inevitable, but if you are well organised these are far easier to manage.“ Susan Wong SGM Head of Scientific Conferences

Top tips from the SGM HEAD OF Scientific Conferences This article is aimed at early-career researchers 10 RULES FOR Planning and attention to detail is extremely important give me some idea of how much delegates might need to pay. who are thinking about organising a scientific ORGANISING A SCIENTIFIC when organising a conference. There are many elements to Attracting funding can be tricky. I recommend asking consider; for example, the theme of the conference, the target senior researchers for information on their contacts (e.g. conference. Some general tips and information CONFERENCE FOR EARLY- audience and a suitable venue. Susan Wong reflects on two who do they buy their laboratory consumables from?). With CAREER RESEARCHERS* are given, including the top tips of the SGM Head aspects: budgeting and sponsorship. their permission, you can then contact the companies with ‘I Rule 1 Opportunity for discussion was given your details by …’. This is more likely to receive a of Scientific Conferences, Susan Wong. Two early- Budgeting is the most important thing response than a ‘to whom it may concern’ request. I suggest I find preparing the budget is one of the hardest aspects of career researchers who have ‘been there, done (but the science helps thinking broadly about the sponsorship opportunities you conference planning because there are numerous variables attract attendees) offer. Don’t just think about sponsors being provided with an which can be difficult to estimate. There are the obvious costs that’ describe their experiences. Rule 2 Allow for plenty of exhibition stand on the day or having their logo featured on that are easy to identify, such as speaker travel, venue hire and planning time the webpage and opening slide for the speaker whose travel food. However, to help me identify many of the hidden costs Rule 3 Study all potential financial costs they contributed to. Could you offer the opportunity to I do a walk through of the event from the delegate’s point of issues affecting your event include marketing materials in the delegate pack, or provide view. For example, the delegate will arrive at the registration delegates with a branded pen or notebook (that’s one less Rule 4 Create a balanced desk to register (expense = signage, name badge, delegate cost for your budget)? If you are having an exhibition area, it agenda (that supports the pack). Then they will make their way to the first session is extremely important that the sessions keep to time as you achievement of Rule 1 in (expense = more signage) to listen to talks (expense = AV want to make sure that delegates arrive in the exhibition area different ways) support, water for speakers and chair) and so on. Rule 5 Carefully select your when you said they would so your (paying!) exhibitors have keynote speakers (not just Attracting sponsorship and grants ample opportunity to talk to them. for their interesting and Once I have established my outgoing costs, I can then offset Also check out organisations such as SGM who offer topical research, but who against any sponsorship secured. The remaining balance will grants to support conferences. are approachable and will Some things (but not everything) you will need to think about interact positively with the – Who will book the speakers’ travel and – Set clear deadlines for the programme On the day Photo: David Martin conference delegates) accommodation? Specify in advance book and print it as late as possible. – Have a plan. Make sure the members of Scientific conferences help drive that are run by early-career researchers for Rule 6 what expenses will be covered. – How will you evaluate the event the organising committee – Do a health and safety check of the the process of science (and scientists’ early-career researchers. Such meetings – Even if there is no registration fee, (on-the-day form, online survey)? have delegated roles and venue. careers) by giving researchers an allow scientists at the start of their careers have a pre-registration system to give 2 weeks before the event communicate regularly – Greet speakers and session chairs. opportunity to disseminate their to interact with others in similar positions, an idea of the number of delegates – Send venue details to exhibitors with Rule 7 Identify your target – Include time for cleaning up. research, get feedback and learn about take heart from learning that they are so you have enough seats, food and information on deliveries, parking audience and advertise new research tools and ideas. While having the same problems, and meet their drinks (but not too much). permits, set-up and shut-down times After the event the internet has improved the ways peers and collaborators of the future. Rule 8 Exploit social media – Will you allow people who haven’t pre- and what’s included. – Thank-you letters for exhibitors, researchers can keep up to date with the Taking on a role in the organisation of Rule 9 Prepare for emergencies registered to turn up on the day? How – Send information to speakers with speakers and session chairs. latest findings and discuss these with such an event affords the early-career Rule 10 Make the impact of your will the registration desk handle that? venue directions, phone number and fellow researchers, there is still great researcher even greater networking conference last – Will all abstracts submitted be a reminder of the time and location of SGM has example documents from value in attending meetings because of opportunities with both speakers and *Adapted from 10 rules accepted or will there be a review their presentation + facilities available. its own events which we are happy to the formal, and particularly informal, delegates and allows them to develop for organising a scientific process? Give reviewers deadlines. 1 week before the event share with members organising their opportunities to interact face-to-face with their skills in areas such as leadership conference (http://bit.ly/ own event. Contact conferences@ other scientists. This is particularly true for and communication and to learn the – Will you supply session chairs with a – Meet with ‘on the day’ helpers so UUgSFq) sgm.ac.uk the increasing numbers of conferences professionalism of managing events. clock to ensure good timekeeping? everyone knows what to do and when.

44 Microbiology Today Feb 2013 Microbiology Today Feb 2013 45 Photo: David Martin Photo: David Martin MY EXPERIENCE There was a morning and afternoon and supplier companies who were efficient and conciliatory. My tip for session of talks, and a poster session offered trade stands or advertisements. others who get involved in organising a over lunch. The event was attended As an organiser, what I enjoyed conference would be: don’t be afraid to Eleni Karinou – Organising Committee Member, by around 150 PhD students, postdocs most was the stimulating discussions ask other people for their opinion. 3rd Annual PiCLS Symposium, University of Dundee and group leaders, mostly from the with the rest of the committee during College of Life Sciences. The invited the preparation of the symposium and http://picls.lifesci.dundee.ac.uk/ The PhD Student’s Association in solely by students and decided to get speakers were proposed by students the team work. Our biggest challenges symposium2012/index.html the College of Life Sciences (PiCLS) is involved. and staff from the College. Delegates were raising money and finding a day a proactive team of students facilitating The organising committee of the were able to submit abstracts for suitable for all our busy speakers. The SGM supported this event by offering networking between PhD students in 2012 Symposium consisted of 9 people, oral presentation or posters, with experience was at times stressful and funds from the Student Society different subject areas. PiCLS organises all PhD students within the college and, presenters selected by principal tiring, but it was a lot of fun. It required Sponsored Lectures scheme (www. Photo: David Martin an annual symposium where eminent like me, most of them were organising investigators of the College. On the good organisation and communication sgm.ac.uk/grants/sssl.cfm) towards researchers in biological sciences are a conference for the first time. I was day of the symposium, the invited skills (making sure there was lots of the travel and accommodation costs invited to speak and network with responsible for finding sponsors for the speakers helped us choose prize communication between members of Professor Pascale Cossart, Institut students. I attended the symposium speakers’ travel expenses. winners from the presenters. The of the organising team was really Pasteur, and offering a prize for the in 2011 and was intrigued by the The 3rd Annual PiCLS Symposium event received sponsorship from important for the success for the event) best poster on a microbiological topic idea of a symposium organised was a 1-day event held on 6 July 2012. various scientific societies, journals and I feel it has helped me to be more presented by a registered PhD student.

MY EXPERIENCE If you have any other topics that you would like to see featured in Robert Ryan – Co-chair, Young Microbiologists Symposium on Microbe Microbiology Today as a ‘How to’ Signalling, Organisation and Pathogenesis 2012, University College Cork article, please email k.mcgregor@ Photo: Heather McLaughlin sgm.ac.uk

In 2008, I was invited to speak at and senior scientists in the field, and need arises. Organising these events has nine ‘hot-spot’ poster talks), and institutions, these types of events the John Innes Centre Young facilitate future collaborations. improved my ability to delegate and my two lunchtime poster sessions. Each showcase the work going on in the Microbiologist Symposium. It was I organised the inaugural event fund-raising skills, and has taught me delegate had to present a poster. department to a wide audience and a great event, but was only for in 2009 and co-chaired the second the importance of patience, trust and Thanks to the support of our sponsors, can be an excellent recruitment tool to researchers at Norwich Research Park. event in 2012 (thanks to Dr Delphine planning in conference organisation. I we were able to set the registration attract postdocs and students. It made me think that an open event Caly my co-chair and to members of feel the experience of organising these fee at only €25 and to offer a number for young microbiologists was missing the research group who helped with events has helped both with my own of prizes for best poster and best www.ucc.ie/yms2012/index.html in the microbiology landscape. For the preparation and on the day). The research and in progressing my career. short talk. this reason I instigated the Young experiences of 2009 did prepare me for The YMS on Microbe Signalling, From the event, I really enjoyed SGM sponsored the lectures of Microbiologists Symposium (YMS) the level of work expected in running a Organisation and Pathogenesis 2012 watching junior scientists ‘put it up’ Professor Cynthia Sharma, University at University College Cork. The YMS good event. However, the various issues attracted over 120 participants from to the gathered eminent scientists of Würzburg, and Dr Trevor Lawley, was intended to bring together and problems that arose in running more than 15 countries, ranging from and seeing those eminent scientists Wellcome Trust Sanger Institute, young microbiologists and to provide the event the second time round were first-year PhD students to starting dispensing sage advice during the from the Regional Meetings Grants an opportunity for these scientists very different and highlighted that, in principal investigators. The 2-day event. I really think that having a scheme (www.sgm.ac.uk/grants/ to present their work and receive organising a conference, you can never programme included three keynote platform for junior scientists to present regional.cfm). constructive feedback, to network with predict the problems you will encounter, talks, five plenary sessions (four on their work to a broad audience is key other students, postdocs, young PIs so you have to be prepared to adapt as predefined topics, one featuring for them to develop as scientists. For Photo: Heather McLaughlin

46 Microbiology Today Feb 2013 Microbiology Today Feb 2013 47 interview

Professor Harald zur Hausen

Nobel Prize winner and distinguished virologist Professor or even in some cases, like human immunodeficiency virus 1 and 2, they Harald zur Hausen has been awarded the 2013 SGM act indirectly, and these infections are Prize Medal (see p. 8). In this interview with Professor also very difficult to prevent because, again, there is a high mutation rate in David Blackbourn, he reflects on his career and offers his those viruses. opinions on some issues currently facing virologists. In other cases, such as Epstein–Barr virus and human herpes virus type What inspired you to pursue a of their career wishing to follow in 8, vaccines could be developed. The Q career in microbiology? your footsteps in microbiology? present non-availability of such vaccines Since my days as a schoolboy I To select an original aspect of is probably due to the lack of interest by A was interested in questions related A research, to work persistently the pharmaceutical industry. to microbiology and cancer. This was and not to trust too much in prevailing probably triggered by reading some of dogmas. Are there more oncogenic human the biographies of well known scientists viruses yet to be discovered, or like Louis Pasteur and Robert Koch. Given the increasing emphasis Q more links between known viruses and on funding translational research, Q cancer yet to emerge? what is the best way to ensure ‘basic’ What challenges did you face In my opinion it is worthwhile to science research continues? Q during the development of your search intensively and carefully Clearly, we need basic research A career? for viruses linked to cancer, particularly in order to successfully translate Every scientist experiences some A whenever the epidemiology may hint to research for clinical application. If we do ups and downs during the lifespan relationships between infectious events A not support basic research, we will have of such activities. Clearly, there was and cancer development. very little to translate. some scepticism initially when we started to work on the question on There’s been a vaccine for viruses causing human cancers, but the ‘high-risk’ types of human during the past decades this has Q papillomavirus that cause cancer of the gradually faded away. cervix for several years and a hepatitis B virus vaccine for many years. Why How do the challenges differ for do you think vaccines against other Q those developing their careers oncogenic human viruses have yet to today? be implemented, when the presumptive I do not believe that the challenges health care benefits would be so A differ very much today from those significant? which I experienced during my career. The problem with some of the A other oncogenic human viruses What advice would you give is that they mutate quite rapidly Q to scientists in the early stages and quickly (e.g. hepatitis C virus), H. zur Hausen. Armin Kübelbeck

48 Microbiology Today Feb 2013 Microbiology Today Feb 2013 49 Reviews

Horizontal Gene Transfer Two-component Systems in Bacteria Rhabdoviruses: Molecular Taxonomy, Evolution, in Microorganisms Edited by R. Gross & D. Beier Genomics, Ecology, Host–Vector Interactions, Edited by M. Pilar Francino Published by Caister Academic Press (2012) Cytopathology and Control Published by Caister Academic £180.00 pp. 426 ISBN 978-1-90823-008-9 Edited by R.G. Dietzgen & I.V. Kuzmin Press (2012) Two-component signal transduction systems (TCSs) are common amongst bacteria. Published by Caister Academic Press (2012) Over the past 15 years or so, sequence data have revealed the widespread Polar Microbiology: £159.00 pp. 202 £159.00 pp. 276 ISBN 978-1-90823-011-9 ISBN 978-1-90823-010-2 occurrence and importance of these systems, and notably the variation and atypical Life in a Deep Freeze features displayed by many systems. This explosion of information has led to a As with many virus families, the number of newly identified species Edited by R.V. Miller & L.G. Whyte As an expert on bacterial plasmids I can re-evaluation of how they should be classified and organised, to considerations of that are classified into one of the genera within the Rhabdoviridae is be guilty of thinking about Horizontal Gene the atypical and more complex multi-component systems and to a realisation of ever-increasing, as is the public health threat posed by this family – only Published by American Society for Transfer (HGT) in terms of the elements and the profound roles of these systems in bacterial cell physiology. This volume draws last month the isolation of a novel Rhabdovirus (Bas-Congo virus) linked Microbiology (2012) processes that make it happen rather than on some selected examples of TCSs to illustrate current advances in knowledge. to an outbreak of acute haemorrhagic fever in the Democratic Republic US$159.95 pp. 312 ISBN 978-1-55581-604-9 its consequences for the transferred genes or of Congo was reported. Whilst this is too recent to be included here, The editors bring together a series of well-written reviews by highly regarded This book is derived from the 4th Polar and Alpine their recipient genomes as this book does. It this book nevertheless provides an up-to-date, if rather dry, account researchers, starting with how TCSs are classified and organised, and current Microbiology conference in Banff (2008), one of a is a refreshing stimulus that considers HGT of this family of viruses covering all six genera and six isolates awaiting understanding of structural knowledge, and moving on to novel aspects of signal series of meetings that began in 2004 in Finland and from many perspectives and is the perfect official classification. For each virus there is a keen focus on evolution, transduction mechanisms, TCS function and gene regulation. Roles for phosphatase have grown steadily in popularity. As a result of broad resource to justify teaching bacterial genetics, phylogenetics, epidemiology and methods for limiting morbidity and activities, orphan and atypical response regulators, antikinases, ‘connectors’ representation of the community, this is a well balanced not as a means for mapping genomes, but mortality. The level of detail and factual style adopted throughout that link systems and multi-component systems are all described, together with and up-to-date presentation of current thinking in the to understand the processes that are driving means it is not a book you would pick up to read on a whim but rather important examples of systems in pathogenic and multicellular species. This book field. Of particular interest are sections on genome and their evolution. This book is a valuable source use for reference. It will be of particular interest to those individuals is an excellent choice for graduate-level education and researchers in the field and expression analysis, Antarctic metagenomic studies, of ideas, facts and references with which to who are intimately involved with these viruses and those who are would be a useful addition to any research group, department or university library in subglacial environments and cold-active biomolecules develop such new teaching resources. joining the field, for whom it would make an excellent resource. a research-active institution or pharmaceutical company. in biotechnology. The layout follows a logical I will be recommending that our library Mary Phillips-Jones, University of Central Lancashire Edward WrigHT, University of Westminster progression from taxonomic diversity, through molecular buys copies to be accessed adaptations to ecology and then future challenges. It is by students ranging from Career Planning for Research Bioscientists a good reference source and contains many useful and enthusiastic first-year Microbes: Concepts and Applications By Sarah Blackford informative tables, such as summaries of primers used, undergraduates taking my By P.S. Bisen, M. Debnath & G.B.K.S. Prasad reports of sub-zero metabolic activity, relevant genomes Genetics course to PhD Published by Wiley-Blackwell (2012) Published by John Wiley & Sons Limited (2012) sequenced, molecular adaptations and biodiversity students researching topics £199.99 pp. 192 ISBN 978-1-4051-9670-3 £133.00 pp. 724 ISBN 978-0-47090-594-4 studies. The reference lists cite work from most, if not for a dissertation. Although Sarah Blackford draws on her years of experience coaching bioscience This new book, written by three authors who collectively possess a wealth of experience in the field, all, of those present at the meeting and could be said not rich in figures, the researchers on careers and career planning to produce this guide. is a comprehensive text covering subjects as diverse as medical microbiology, microbes in agriculture to present an introduction to an exciting era in polar text is clear with good The book explains career planning approaches, gives practical ways and the use of micro-organisms as tools for industry and research. In this respect, at less than 700 microbiology. subheadings and is easy to increase your self-awareness, and ideas for how to be proactive pages, this text must be considered to be a concise overview and this is reflected in the somewhat to dip into. in enhancing your employability – and all written with reference to David Pearce, British Antarctic Survey basic nature of the text and diagrams. On a positive note, however, the breadth of the text provides Chris Thomas, the experiences and opportunities available to bioscience doctoral the reader with a solid basic introduction to the world of microbes. University of Birmingham students and postdocs. It is this feature which distinguishes this book from others This traditional text is directly aimed at undergraduate students. Unlike many new texts of this type, in the marketplace that discuss these issues for a generic audience. Consideration is however, there is no supplementary information-technology-based material. Coupled with a price given not just to jobs in academic research, but a whole range of possibilities, both tag of over £130, access is likely to be limited to copies located in institutional libraries and these inside and outside science, supported by detailed career profiles of 20 PhD-qualified two factors may result in the text missing its target audience. Given the price, it is perhaps also bioscientists. Whether you already have ideas about what type of job you want, or disappointing that the text and figures are entirely in black and white, which are unlikely to engage have no idea what your options are, you will find something in this book to make you students new to the field. think about taking the plunge towards your next job in a proactive and productive way.

sue lang, Glasgow Caledonian University iStockphoto Karen McGregor, SGM

50 Microbiology Today Feb 2013 Microbiology Today Feb 2013 51 Comment New frontiers in scientific publishing leighton chipperfield iStockphoto Around the world, the ways in which scientific articles online, but spending less time reading each one. Yet, infrastructure limitations in some developing countries research is published and accessed has begun mean any type of e-access remains problematic. And a to attract significant attention. I joined SGM in hardcore of personal customers still like to receive their August 2012 with an exciting remit: to modernise print journal. Whilst providing this choice of ‘delivery channel’ is our publishing business and prepare SGM for the desirable, it comes at additional cost to the publisher – challenges and opportunities that lie ahead. So and ultimately the reader. It is clear that most if not all UK Plant scientific publication will ultimately move to a fully digital what is happening and how is SGM responding? environment. The speed with which print dies is up for 1. Planning for a sustainable future debate! Sciences Like many learned societies, SGM is actively involved in 3. Global authorship the dialogue on Open Access (OA). Across science, the The transition of journal usage from print to digital over proportion of OA articles is increasing, although most the past 10 years has coincided with the widespread Federation research is still published in subscription-based journals. adoption of online submission and peer-review systems. With governments, funding bodies and even institutions These developments have opened up a global market of all developing their own OA policies, the global picture (UKPSF) authors and readers for previously ‘local’ journals. remains complex, and it seems likely that different The last decade has also seen the growth of certain geographies and disciplines will move at their own pace. countries’ output of research papers, primarily driven by For societies like SGM, OA presents both challenges R&D investment. Notably, China has consistently increased and opportunities. Under the ‘Gold’ OA model supported PlantSci2013 Conference its article share over the past 15 years, now accounting by the UK Finch Report, revenue to a journal would shift for 1 in 10 published papers – surpassing traditional big from traditional subscriptions to author fees underwritten players such as the UK, Japan and Germany. Along with by funding bodies. For SGM, the main opportunities of Brazil and India, papers from China form the highest area Dundee, 16–17 April 2013 OA lie in increasing usage of our existing journals, and of submissions growth for SGM’s titles. At SGM we will providing an alternative model for launching new titles be engaging more proactively with microbiology authors in future. worldwide, ensuring that we bring readers the best Full details of the programme can be found at Whatever model proves sustainable for an individual microbiology research from wherever it may emanate. publication, the only certainty is that authors will www.plantsci2013.org.uk/programme continue to be its lifeblood. Now more than ever, And that’s just the tip of the iceberg. We’re also societies like SGM need to ensure their publications are considering how developments such as the ‘semantic UKPSF relevant and compelling, offering a high level of service web’, text and data mining, and social media can make Society of Biology, Charles Darwin House to our valued authors and doing more to ensure they our content ever more rich and discoverable. return again and again. There has never been a more exciting time to be 12 Roger Street, London WC1N 2JU involved in publishing great science – and we’d like you to Tel. +44 (0)20 7685 2567 2. Digital is here get involved. After all, these are your publications. www.plantsci.org.uk When I entered scientific publishing in 1999, print was Look out for more information on the new SGM still king. Speak to a librarian now and the message website. In the meantime, why not follow us on Twitter The UK Plant Sciences Federation is a special has changed dramatically. The functionality, speed, at @PublishingSGM to hear first about some exciting interest group of the Society of Biology searchability and measurement of the online journal had announcements! operating with financial support from the already begun to make print redundant before the dawn Society of Experimental Biology and The of mobile. Latest data supports the change in reading leighton chipperfield, Head of Publishing at SGM Gatsby Charitable Foundation habits, showing that researchers are accessing more (Email [email protected];Twitter @leightonc)

52 Microbiology Today Feb 2013 Caister Academic Press New Books www.caister.com Oral Microbial Neurospora Malaria Parasites Ecology Genomics and Molecular Comparative Genomics, Current Research and Biology Evolution and Molecular Edited by: DP Kasbekar, K New Perspectives Biology McCluskey Edited by: JM Carlton, SL Edited by: NS Jakubovics, RJ x + 294 pp, January 2013 Perkins, KW Deitsch Palmer Jr. ISBN: 978-1-908230-12-6, x + 280 pp, February 2013 xii + 232 pp, April 2013 $319/£159 ISBN: 978-1-908230-07-2, $319/£159 ISBN: 978-1-908230-17-1, $319/£159 Carotenoid biosynthesis, polysaccharide Comprehensively reviews the current An essential text covering oral micro- deconstruction, genome biology, genome advances in Plasmodium comparative biology, bacterial communities, biofilms, recombination, gene regulation, signal genomics, highlighting new insights into dental caries and periodontal disease. transduction, self-recognition, development, parasite evolution and molecular biology. and circadian rhythms and mutation. Bionanotechnology Foodborne and Biological Self-assembly Rhabdoviruses and its Applications Molecular Taxonomy, Waterborne Bact- Edited by: BHA Rehm Evolution, Genomics, x + 310 pp, February 2013 erial Pathogens ISBN: 978-1-908230-16-4, Ecology, Host-Vector Epidemiology, Evolution $319/£159 Interactions, Cytopathology and Molecular Biology The production of biogenic nanodevices, and Control Edited by: SM Faruque description of biological nanostructures, Edited by: RG Dietzgen, IV Kuzmin x + 318 pp, July 2012 the implied design space and the viii + 276 pp, September 2012 ISBN: 978-1-908230-06-5, $319/£159 applications in medicine and technology. ISBN: 978-1-908230-11-9, $319/£159 Reviews pathogenic properties, population A must-read book for all virologists working on genetics, virulence genes, evolution, these and related negative sense RNA viruses. drug resistance, epidemiology, detection, Real-Time PCR in identification and control strategies. Food Science Horizontal Gene Current Technology and Yersinia Applications Transfer in Systems Biology and Edited by: D Rodriguez-Lazaro Microorganisms Control c. 280 pp, January 2013 Edited by: MP Francino Edited by: E Carniel, BJ ISBN: 978-1-908230-15-7, $319/£159 x + 202 pp, September 2012 Hinnebusch An indispensable manual for the food ISBN: 978-1-908230-10-2, x + 246 pp, July 2012 industry and for anyone involved in the $319/£159 ISBN: 978-1-908230-05-8, detection of foodborne pathogens. Expert authors have contributed novel $319/£159 work and comprehensive, up-to-date Leading Yersinia researchers review the reviews on the most topical aspects. hot topics in the systems biology and Bacterial Gene control of these important bacteria. Regulation and Microbial Transcriptional Ecological Theory Stress Response Networks Current Perspectives in Microbiology Edited by: MM Babu Edited by: LA Ogilvie, PR Edited by: JM Requena c. 280 pp, January 2013 Hirsch x + 436 pp, June 2012 ISBN: 978-1-908230-14-0, $319/£159 viii + 112 pp, September 2012 ISBN: 978-1-908230-04-1, The latest research observations and ISBN: 978-1-908230-09-6, $240/£120 $360/£180 current theories on transcriptional Synthesises current viewpoints and Comprehensively reviews the regulation and gene circuits in bacteria. knowledge and shows how the application recent findings that have greatly advanced the of macro-ecological theory enhances our understanding of stress response systems. understanding of microbial ecology. “well and sensibly illustrated” (Micro. Today) Bioremediation of Mercury Two-Component COMING SOON Current Research and Industrial Applications Systems in • Cold-Adapted Microorganisms Edited by: I Wagner-Döbler Bacteria • Prions xii + 144 pp, January 2013 Edited by: R Gross, D Beier ISBN: 978-1-908230-13-3, $240/£120 xii + 426 pp, August 2012 • RNA Editing The latest research including the genetic ISBN: 978-1-908230-08-9, • Microbial Efflux Pumps engineering of bacteria and plants, and a $360/£180 discussion of options for the future. Current information including structure-function • Cytomegaloviruses analysis, sensing mechanisms, atypical systems, stress responses, developmental www.caister.com processes, virulence and symbiosis. www.caister.com

ORDER FROM (UK/Europe): Caister Academic Press, c/o Book Systems Plus, 1st Floor, 8 Hill St., Saffron Walden, CB10 1JD, UK Tel: 01799 524458 Fax: 01799 524459 http://uk.caister.com 54 Microbiology Today Feb 2013 (USA): Caister Academic Press, c/o ISBS, Inc., 920 NE 58th Avenue, Suite 300, Portland OR 97213-3786, USA Tel: 503 287-3093 Fax: 503 280-8832 http://usa.caister.com