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April 15, 2014

Videos and photos from the Pallen Inaugural

Follow-up to Nothing in Microbiology makes Sense except in the Light of Evolution from The Microbial Underground

Live streamed version:




Slidecast version (better sound quality and no need to look at my ugly mug!)


Photos from the day here:

https://www.dropbox.com/sh/ao2xx91qrjl8rtu/2FijtEacI9


Nothing in Microbiology makes Sense except in the Light of Evolution

Writing about web page https://storify.com/mjpallen/palleninaugural

Here is online companion to my Inaugural Lecture.



September 11, 2013

Inaugural Symposium to celebrate the establishment of the Division of Microbiology and Infection

26-27 September 2013, Warwick Arts Centre, University of Warwick

As well as listening to presentations from researchers showcasing the breadth of our exciting microbiology and infection research here at Warwick, there will be a chance to visit our poster exhibition. Keynote speaker, Professor Gad Frankel, renowned across the globe for his work on mechanisms of bacterial colonisation and infection, will speak about ‘The interplay between the Escherichia coli type III secretion system effectors’.

Don’t miss the exclusive premiere performance of the Rap Guide to Infection, written and performed by Baba Brinkman (Canadian rap artist, writer, actor, and tree planter) specifically for this inaugural event . Baba is well known for his award-winning hip-hop theatre shows, including The Rap Guide to Evolutionand The Canterbury Tales Remixed, which interpret the works of Darwin and Chaucer for a modern audience.

Spaces are still available for the symposium and evening dinner. Book your place now @ http://tinyurl.com/npmc6gg 

Unfortunately all the accommodation we have secured at preferential rate has been allocated. However, if you would like to book and pay for your own accommodation, please email reservations@warwick.ac.uk with your requirements.


April 09, 2013

Diagnostic metagenomics in bacteriology: our proof–of–principle paper

Writing about web page http://jama.jamanetwork.com/article.aspx?articleid=1677374

A Culture-Independent Sequence-Based Metagenomics Approach to the Investigation of an Outbreak of Shiga-Toxigenic Escherichia coli O104:H4

page1image3176 page1image3336

Nicholas J. Loman, MBBS, PhD Chrystala Constantinidou, PhD Martin Christner, MD
Holger Rohde, MD Jacqueline Z.-M. Chan, PhD Joshua Quick, BSc Jacqueline C. Weir, MSci Christopher Quince, PhD Geoffrey P. Smith, PhD Jason R. Betley, PhD Martin Aepfelbacher, MD Mark J. Pallen, MA, MD, PhD

JAMA. 2013;309(14):1502-1510



Ever since Hans Christian Gram and Robert Koch published their seminal papers in the early 1880s (1, 2), clinical diagnostic bacteriology has relied primarily on microscopy and culture in the laboratory to detect, identify and characterize human pathogens. Yet, there are many drawbacks to the use of these nineteenth-century approaches in the twenty-first century. Some important pathogenic bacteria can be isolated only after prolonged incubation (e.g. Mycobacterium tuberculosis) or under exacting culture conditions (e.g. anaerobic or microaerophilic organisms like Clostridium difficile or Campylobacter jejuni); in fact, several important pathogenic bacteria cannot be grown in vitro at all, including those that cause syphilis or leprosy. Variation in cultural requirements creates a need for many different culture media and many different procedures when processing clinical specimens and isolates—this results in complex and onerous workflows and a requirement for skilled staff (3).


So, what’s the solution? Well, 20 years ago, the polymerase chain reaction (PCR) brought the promise of a new model of diagnosis that might take us beyond the need for microscopy and culture.(4, 5) Gene-specific tests can be used to detect specific genetic determinants of importance in virulence and antimicrobial resistance. However, this approach suffers from the problem of finding only what you are looking for, so is not ideal for finding unknown virulence or resistance factors or even new combinations of known genetic determinants. Also, like culture, this approach requires a plethora of protocols each optimized for a particular pathogen or gene.


Today, we have published a paper in the Journal of the American Medical Association (JAMA) that presents proof of principle for a new approach that might augment or even replace the Koch-Gram paradigm that has dominated diagnostic bacteriology for so long. Metagenomics—the recovery of sequences directly from mixed populations of organisms without culture—has already proven a powerful approach to the analysis of complex microbial communities, particularly with the advent of high-throughput sequencing, which has delivered ultra-deep shotgun sequencing with unprecedented ease and cost-effectiveness (6, 7). This approach has seen widespread application in environmental microbiology and most recently in the cataloguing and investigation of the microbial communities associated with humans and other animals (8-10).


Diagnostic metagenomics—high-throughput sequencing of DNA extracted from clinical samples—provides an attractive alternative to the Gram-Koch paradigm in medical and public health bacteriology, avoiding the artifacts and inconvenience of culture and PCR, while potentially providing a simple but highly informative, one-size-fits-all approach to sample preparation and analysis. We have explored the potential of this approach by sequencing DNA extracted from a variety of human fecal samples, collected during and after the German STEC outbreak of 2011, in the hope of detecting and characterizing the outbreak strain and other bacterial pathogens without the need for microscopy, culture or PCR.


So how well did we do? Well, you can find out for yourself by reading the paper and associated commentary and blog post (coming soon from Bridget Kuehn) on the JAMA web site! Do not be put off by David Relman’s downbeat list of caveats: he is merely letting clinicians know that this is not a technique that is going to work out of the box in a routine diagnostic lab in the next week or two. But I would like to hope that there are parallels with the Wright brothers at Kitty Hawk: one day diagnostic metagenomics will be as routine as heavier-than-air human flight!


References

1. Koch R. Zur Untersuchung von pathogenen Organismen. Mitth. a. d. Kaiserl. Gesundheitsampte 1881; 1: 1-48. English translation Methods for the study of pathogenic organisms In Milestones in Microbiology: 1556 to 1940, translated and edited by Thomas D. Brock, ASM Press. 1998, p101.

2. Gram HC. Über die isolierte Färbung der Schizomyceten in Schnitt- und Trockenpräparaten. Fortschritte der Medizin 1884; 2: 185–189. English translation in Methods for the study of pathogenic organisms In Milestones in Microbiology: 1556 to 1940, translated and edited by Thomas D. Brock, ASM Press. 1998. 1884.

3. Didelot X, Bowden R, Wilson DJ, Peto TE, Crook DW. Transforming clinical microbiology with bacterial genome sequencing. Nat Rev Genet. 2012;13:601-612.

4. Pallen MJ, Butcher PD. New strategies in microbiological diagnosis. J Hosp Infect. 1991;18 Suppl A:147-158.

5. Fredericks DN, Relman DA. Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates. Clin Microbiol Rev. 1996;9:18-33.

6. Gill SR, Pop M, Deboy RT et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355-1359.

7. Snyder LA, Loman N, Pallen MJ, Penn CW. Next-generation sequencing--the promise and perils of charting the great microbial unknown. Microb Ecol. 2009;57:1-3.

8. Caporaso JG, Lauber CL, Walters WA et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6:1621-1624.

9. Qin J, Li R, Raes J et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59-65.

10. A framework for human microbiome research. Nature. 2012;486:215-221.



April 03, 2013

Warwick Medical School establishes a new £4–million Division of Microbiology and Infection


Welcome to our new blog, the Microbial Underground, a subversive, provocative, informative blog from Warwick's Division of Microbiology and Infection, blending enthusiasm with scepticism for all that is new in the microbial sciences, with a focus on fast-moving, high-throughput technologies!

Warwick Medical school has this week established a new Division of Microbiology and Infection, with over £4 million of investment launching a vibrant new research community of around twenty staff and students, headed up by me, Mark Pallen.

I would like to think the rationale for such an initiative is self-evident: after all, there are more microbes on our planet than there are stars in all the galaxies in the observable universe! And microorganisms have played a pivotal role in the history of science, for example in establishing that DNA carries genetic information. Millions of diabetics now rely on biotechnological exploitation of a bacterium, E. coli, to make insulin.

But of course, microbes are not just friends but also foes, as evidenced by the havoc wrought in Germany in 2011 by a Shiga-toxin-producing strain of E. coli .

I am joining the Division as Professor of Microbial Genomics. My own interests are fairly wide-ranging and span the divide between basic and applied research in bacteriology, with a particular focus on using genome sequences to understand how bacterial pathogens evolve, spread and cause disease. Recently, I have been worked closely with industrial and international collaborators to exploit new DNA sequencing approaches to identify and characterize the strain of E. coli that caused such a devastating outbreak of infection in Germany, with papers in NEJM and Nature Biotech. I am also author of a popular book, The Rough Guide to Evolution and was chief instigator behind Baba Brinkman's Rap Guide to Evolution, a provocative celebration of Darwin’s legacy through the medium of Hip Hop: I star in the video for I'm a African!

But enough of me: this initiative brings a wealth of new academic talent to the University of Warwick!

AchtmanLet's start with Professor Mark Achtman, who is about to joins us from Cork in Ireland. Mark brings a world-class reputation in the field of bacterial evolution and epidemiology, as evidenced by high-impact papers in the most prestigious scientific journals, including Science magazine (check him out on Google Scholar).

I have heard Paul Keim describe Mark as a "force of nature"! Mark has used his formidable research talents to attack some of the big questions about human existence—for example, using DNA sequences from a bacterium that lives in our stomachs to work out how humans spread out of Africa to people the world, or exploring the origins, evolution and spread of the bacterium that causes the plague, including the Black Death pandemic which killed around a third of the inhabitants of Europe in the fourteenth century. Professor Achtman harnesses robots and computers to laboratory research to create an exhilarating high-throughput approach to microbiology (check out this video from his former life in Cork)!

Associate Professor Nick Waterfield(@nick_waterfield) will soon be joining us from the University of Bath. Dr Waterfield brings a broad research vision to investigations of how bacteria interact with the organisms they infect, using high-throughput screens in insects and other invertebrates to shed light on important human infections. Check out Nick's old web page at Bath here.

Several authorities, including the Academy of Medical Sciences, the Wellcome Trust and the Medical Research Council, have stressed the urgent need for capacity building in academic clinical microbiology. The need for new investment in this area has been reinforced by the recent headline-grabbing report from the UK’s Chief Medical Officer Dame Sally Davies, ramming home the need for a better understanding of the evolution and spread of multi-drug resistant pathogens and how we can best avoid and treat the infections they cause. With all that in mind, Warwick Medical School is delighted to recruit a world-class clinical academic, Dr Esther Robinson to a Clinical Associate Professorship. Dr Robinson comes not only with a DPhil from the University Oxford, but also with accreditation to work as a consultant medical microbiologist in the NHS. With clinical sessions at the Heart of England NHS Trust, she will act as an important bridge between the new Division and translational research into clinical microbiological problems.

Several early-career academics are also joining the new Division:

  • Dr Emma Denham(@gingermicrobe) is joining us at Assistant Professor Level, bringing with her basic and translational research expertise in Gram-positive bacteria (as evidenced by two Science papers!). We anticipate making one additional appointment at this level.
  • Dr Chrystala Constantinidou and Dr Andy Millard are taking up Principal Research Fellowships, with an emphasis on high-throughput DNA sequencing and analysis.

The new Division will also benefit from state-of-the-art laboratory facilities, including a MiSeq high-throughput sequencing instrument.

Our aim is for the new Division to have a global reach. With that in mind, we have already initiated links with Dr Martin Antonio at the MRC Centre in Gambia, who now has a visiting academic position within the new Division and will co-supervising two PhD students here. We are also keen to see the new Division act as a starting point for a new campus-wide Research Centre that will integrate laboratory-based research with a much wider range of research activities, from epidemiology to the history of medicine, from medicinal chemistry to clinical infectious diseases, while also catalyzing links with other key regional, national and global stake-holders, including the health services, industry, government and NGOs.

To catch up on our news and track our progress, please follow this blog and follow us on Twitter (@WarwickMicrobio), plus follow all of us individually on Twitter too!

Oh, and we do have a web site too, which you can watch being built (but aren't web sites all rather 20th century these days?).

The game's afoot! The excitement begins!


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  • I have just seen this paper on the ~7–thousand–year auroochs genome: http://www.genomebiology.com/20… by Mark Pallen on this entry
  • Hi Chris, You are right that there is nothing implicit in being Open Access that guarantees a right … by Mark Pallen on this entry
  • Good to see it on biorxiv. I didn't fully follow the second point about elife, your criticism seems … by Chris Keene on this entry
  • Congratulations to Professor Achtman. by on this entry
  • Hi Shilp, glad that you found it useful . I used seqtk sample. So if I had 100 reads for 90% seqtk s… by Andrew Millard on this entry
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