I recently had a paper accepted and therefore dutifully registered it on the University’s Symplectic database. This forms a repository for all the publications generated by the university, which is of course a vital tool for summarizing research output (for instance for the Research Excellence Framework). It is required to upload the accepted manuscript, but as many journals do not permit uploading a pdf of the published version, usually the word file of the accepted version is submitted (which makes it a great deal less valuable, as such versions are not combined with figures in an easy-to-read journal format and miss corrections made at the proof stage). I noticed that Symplectic uses Scopus H-factor calculations, which is a shame, as this Elsevier database does a very bad job at that (even worse than Web of Science, see this old post).

For the first time, I checked some of the ‘altmetrics‘ for some of my papers. I have been sceptical about tallying the number of twitter mentions etc: if you are on a paper with lots of tweeting authors and/or in a field where people tend to be more active on twitter (e.g. computational biology), there will be a bunch of those, but in general the number seems small and biased.  The whole online interactivity surrounding publications is usually quite minimal; this must be for a large part because scientists are too busy with their own research to write more than a lazy tweet about research by other people. I do appreciate that the PLoS journals for instance give the opportunity to comment on papers but I hardly see people actually doing that. Anyway, the immediate reason for writing this brief blog post was that one of the altmetrics I noticed, was a youtube video. When clicking it, I saw to my great surprise five North American scientists, led by Dr. Laura Williams, doing an tele-conference journal club about one of my papers (briefly outlined in this blog post). A one-hour dissection of a paper by colleagues for the world to see: scary!

So far, I have only zapped through and luckily it seemed mostly positive. It was quite interesting to see that some points did not come across as well as I hoped they would do, providing an opportunity to reflect on how to better communicate findings.

Although I really should have done some more reading on altmetrics for this post, it’s social media component, albeit interesting, does not seem a very reliable indicator of research impact. There are other altmetrics that seem very promising though. For instance, just the total number of paper views or downloads could be really useful: they are much greater in number and much less time-lagged than citations, making them perhaps a more accurate proxy for interest garnered. (Of course, citations reflect other scientists having actually built on the work, whereas some of the views/downloads will be of people who after reading it might find that the paper has very little value, but still.) Our Symplectic database does list Mendeley and CiteULike reads but does not go beyond this (small) portion of total reads. As some fields have many more workers than others, and of course as older papers have had more time to accumulate views, some corrections could be applied (the same goes for citation numbers, so this is not a unique criticism). PLoS not only gives the raw numbers of paper downloads, but also a little graph on how a paper compares to others published by the same journal in the same field in the same year, which is neat. I will highlight the accepted manuscript in a next blog post as soon as it is published!


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Paper Out: The Ecological Role of Volatile and Soluble Secondary Metabolites Produced by Soil Bacteria

First of all a very happy 2017 to all readers. It will be my new year’s resolution to update the blog more frequently (for instance, I have not blogged about really interesting visits to Prof Haiwei Luo in Hong Kong, the natural product discovery company Selcia in the UK or a talk for the Cornish Microbiological Society with our colleagues at the hospital in Truro….).

Anyway, I was fortunate enough to be invited to contribute (a little bit!) to a review paper on volatile secondary metabolites with lead author Dr. Paolina Garbeva at the Netherlands Institute of Ecology (see here for a short post on a visit last year). Paolina have a collaboration planned for this year which I am very excited about (and which will be documented on the blog). The paper in Trends in Microbiology came out just before the end of 2016, from the Abstract:

The rich diversity of secondary metabolites produced by soil bacteria has been appreciated for over a century, and advances in chemical analysis and genome sequencing continue to greatly advance our understanding of this biochemical complexity. However, we are just at the beginning of understanding the physicochemical properties of bacterial metabolites, the factors that govern their production and ecological roles. Interspecific interactions and competitor sensing are among the main biotic factors affecting the production of bacterial secondary metabolites. Many soil bacteria produce both volatile and soluble compounds. In contrast to soluble compounds, volatile organic compounds can diffuse easily through air- and gas-filled pores in the soil and likely play an important role in long-distance microbial interactions. In this review we provide an overview of the most important soluble and volatile classes of secondary metabolites produced by soil bacteria, their ecological roles, and their possible synergistic effects.

Tyc O, Song C, Dickschat JS, Vos M, Garbeva P. The Ecological Role of Volatile and Soluble Secondary Metabolites Produced by Soil Bacteria. Trends in Microbiology. 2016 Dec 27. cough presentation1

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Living with Environmental Change 2016/2017

I am reaching the end of the semester teaching the module ‘Living with Environmental Change’ together with Professor Lora Fleming. (I have written four blog posts I, II, III and IV last year about the first time we ran this module.) Back then, we had to develop the module from scratch and teach it both on the Penryn campus and the St. Lukes campus in Exeter (a hundred miles east), which made it a lot more work. The experience has been a great deal more relaxed this time around. We have managed to ensnare some excellent guest speakers, ones that have taught before, such as the ECEHHs Dr. Rebecca Lovell who works on the health benefits of the natural environment, and new ones, such as Dr. Anna Harper who works on climate models. Their talks illustrate the breadth of the module: from vibrating diatomic molecules (wiggling CO2 molecules releasing energy causing the greenhouse effect) to Green Gym (taking action to improve the environment while exercising). A great feature of the module is the fact that each student gives a short Pecha Kucha style presentation on their essay topic. This greatly broadens the range of topics that students can learn about, from Aquaculture to Zika, e-Waste, Petridish burgers, heat waves, noise pollution to Blue Carbon (and 35 other topics). We also repeated the excellent tour of the local Wheal Jane mine waste remediation facilities. wgii_ar5_figspm-2I gave a lecture about human pathogens and climate change. I asked each student to do some quick research online and fill out a fact sheet on an assigned pathogen species. Asking the students what facts they found was a nice way to make the lecture a bit more interactive. I asked them not only about the symptoms and treatment of disease, but also whether climate change is expected to impact the occurence of disease. In a lot of cases, the answer is yes. There are many examples of vectorborne diseases moving northwards, eg the Asian tiger mosquito Aedes albopictus is settling in southern Europe with increasing forays into northern Europe. Small outbreaks of Dengue-, Chickungunya- and West Nile fever are already taking place.

Figure 1

Country colouring is based on evidence-based consensus, with green representing a complete consensus on absence of B. pseudomallei and red a complete consensus on presence of B. pseudomallei. Black dots represent geo-located records of melioidosis cases or presence of B. pseudomallei.

Increased water temperatures and reduced salinity (due to increased rainfall and runoff) are strongly correlated with Vibrio infections. Species such as V. parahaemolyticus and V. vulnificus can cause very nasty and sometimes deadly infections and are on the rise in the Baltic (see here). The Fal Estuary around the corner is probably a good habitat too. Burkholderia pseudomallei is another particularly dangerous opportunistic bacterial pathogen that causes a wide range of infections (opportunistic sounds like an understatement; this bug happily infects plants and humans alike). Mainly known to be problematic in South-East Asia and Northern Australia, and also called the ‘Vietnam-time bomb’ for its long incubation time, it can cause very high mortality rates (20-50% even with treatment). Not only does this bug like it warm and moist, it also likes fertilized and saline soils, so warmer weather, sea level rise and  increased agriculture are very likely to benefit this pathogen. This interesting modelling study shows that melidiosis is likely to be greatly underreported, and even endemic in dozens of countries where it has never been reported before. There were many other fascinating examples, including anthrax (Bacillus anthracis) rearing its head in Siberia after the thawing of permafrost and cases of legionaires disease (Legionella pneumophila) associated with increased rainfall. I promise to write a longer blog post next year.


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Paper out: No effect of natural transformation on the evolution of resistance to bacteriophages in the Acinetobacter baylyi model system

A long time coming, but the results obtained in NERC-funded research on evolutionary benefits (or lack thereof) of bacterial transformation have now been published. The work was carried out mainly by research tech Amy McLeman, who has since started her PhD in another group here on the Cornwall campus. On board were local collaborators Pawel Sierocinski, Elze Hesse and Angus Buckling, as well as overseas collaborators Nils Huelter, Gabriel Perron and Pal Jarle Johnsen (see this old post about the latter two). A true team effort! I have lazily pasted the abstract and link to the Open Access paper below:

The adaptive benefits of natural transformation, the active uptake of free DNA molecules from the environment followed by incorporation of this DNA into the genome, may be the improved response to selection resulting from increased genetic variation. Drawing analogies with sexual reproduction, transformation may be particularly beneficial when selection rapidly fluctuates during coevolution with virulent parasites (‘the Red Queen Hypothesis’). Here we test this hypothesis by experimentally evolving the naturally transformable and recombinogenic species Acinetobacter baylyi with a cocktail of lytic phages. No increased levels of resistance to phage were found in the wild type compared to a recombination deficient ΔdprA strain after five days of evolution. When exposed to A. baylyi DNA and phage, naturally transformable cells show greater levels of phage resistance. However, increased resistance arose regardless of whether they were exposed to DNA from phage-sensitive or –resistant A. baylyi, suggesting resistance was not the result of transformation, but was related to other benefits of competence. Subsequent evolution in the absence of phages did not show that recombination could alleviate the cost of resistance. Within this study system we found no support for transformation-mediated recombination being an advantage to bacteria exposed to parasitic phages.

McLeman A, Sierocinski P, Hesse E, Buckling A, Perron G, Hülter N, et al. No effect of natural transformation on the evolution of resistance to bacteriophages in the Acinetobacter baylyi model system. Scientific Reports. 2016;6:37144.

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PhD opportunity: the role of natural antimicrobials in selection for antibiotic resistance

img_5998The NERC GW4 Universities Doctoral Training Program is currently advertising PhD projects. This is a slightly complicated process, but basically comes down to prospective students picking a project offered by scientists working at participating universities and institutions and applying to the program. I (Dr Michiel Vos, offer one of these projects as part of a team of  GW4 colleagues (Prof Will Gaze, University of Exeter, Prof Ed Feil, University of Bath and Dr Ruth Airs, Plymouth Marine Laboratory). Below the project description:

The increasing prevalence of antimicrobial resistance (AMR) in bacteria is one of the most pressing problems in global health care. Selection for antibiotic resistance occurs through antibiotic use in the clinic and community and contamination of the environment with heavy metals, biocides and antibiotic residues. However, AMR mechanisms are ancient and their presence in environments with no or minimal exposure to human activity indicates that not all AMR selection is anthropogenic. It is here proposed to test for the first time whether naturally produced antimicrobials can select for resistance to clinical antibiotics. Virtually all organisms, from bacteria to humans, produce antimicrobial compounds. Selection for resistance to these antimicrobials has the potential to also result in resistance to clinical antibiotics when the same bacterial pathways are targeted. Although the ubiquity of interactions between bacteria and antimicrobial producers offers great potential for the molecular diversification of AMR mechanisms, the extent of cross-resistance between naturally produced antimicrobials and clinical antibiotics has remained virtually unstudied.

Seaweeds form a diverse and abundant component of coastal ecosystems and commonly exhibit antimicrobial activity. Seaweed species are colonized by distinct bacterial assemblages, and this process is at least in part mediated by a high diversity of exuded secondary metabolites. Recent research in my lab (Colclough etal in prep) has demonstrated that Staphylococcus aureus strains that were more resistant to clinical antibiotics were on average also more resistant to seaweed extracts. The fact that seaweeds can select for bacteria that are resistant to their metabolites and the observation of cross-resistance between seaweed antimicrobials and clinical antibiotics suggests that there is potential for seaweeds to select for AMR. This PhD project will 1) test whether distinct seaweeds harbour distinct antibiotic resistance genes using metagenomic sequencing, 2) test whether reservoirs of resistance genes can be transferred from seaweed-associated bacterial metagenomes to opportunistic pathogens using functional metagenomics and 3) identify human pathogens on seaweeds and test whether they are more resistant to antibiotics than conspecifics from other environmental reservoirs using whole genome sequencing.

It is critical to understand natural processes governing selection for AMR in the environment. It has been estimated that there are over six million exposure events to cephalosporin-resistant E. coli through recreational use of coastal bathing water in England and Wales alone, demonstrating the potential risks of environmental reservoirs of AMR to human health. This project will allow a first insight into the potential of species interactions to select for AMR mechanisms that confer cross-resistance to clinically relevant antibiotics.

To be clear: the project below is funded only when YOU decide to select this particular (and excellent) project AND are offered entry to the PhD program. See the DTP site for eligibility details etc and the University of Exeter postgraduate research page to apply. The deadline for application is January 6th 2017.

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The Transition from Class Room to a Year of Research

A guest post my BSc student Michael Tadesse who joined us last year for a lab project:

In the academic year 2015-2016, I undertook a Professional Training Year (PTY) at the European Centre for Environment and Human Health (ECEHH) in Cornwall, UK under supervsion of Dr Michiel Vos. I went into my PTY hoping to gain a better idea of what a career in research would look like. During my second year, I was contemplating pursuing a PhD. So along with the boost a PTY would give to my CV, I would also find out whether I could handle the commitment of a PhD. In this post I will try to reflect on my placement, my problems in adjusting to a new environment and my experiences gathering data once I settled in properly. mtMy activities were based on a previous PTY project that screened a variety of seaweeds for antibacterial potential. We now wanted to test whether our extracts are more, less or equally effective on pathogens that are resistant or susceptible to clinical antibiotics. This depends on whether the mode of action of natural antimicrobials is independent from genes conferring clinical antibiotic resistance. Several resistance mechanisms, such as  those involving drug uptake and efflux, are prone to cause cross-resistance, where an organism displays increased resistance to a second drug. The opposite process is also possible: collateral sensitivity means that an organism that has developed resistance to one drug can display increased sensitivity to a second drug. Promising candidates could be further identified using mass spectrometry to elucidate the nature of compounds in collaboration with another lab, adding a mechanistic component to the project and the opportunity to gain experience in organic chemistry methods. I first created several E. coli mutants using one host strain and several plasmids with resistance genes and GFP or mCherry fluorescence tags.  I obtained them from my lab mate, Dr Uli Klumper. I introduced these plasmids using electroporation or selective mating. The transformed cells were then plated out in selective agar containing the respective antibiotic. Successful mutant colonies were then selected through fluorescence microscopy. This seemed pretty straightforward but I had problems creating the necessary electro-competent host cells or introducing the plasmids. Fortunately, in the end, I managed to find solutions for every obstacle with the help of Uli. Secondly, eleven strains of resistant and susceptible Staphylococcus aureus were obtained from Dr Ruth Massey (University of Bath, UK). Each resistant strain had a susceptible counterpart and the two strains only differed in their respective resistance second part of this project was testing my seaweed extracts against these strains. I performed simple Kirby-Bauer disc diffusion assays. I soaked assay discs in seaweed extract for 24 hours, and dried them in a laminar flow hood for 15 minutes. The discs were then placed on agar plates that were mixed with a E. coli or S. aureus strain. Positive control (imipenem, 4 mg/l) and negative control (60% methanol) discs were soaked and dried in the same way.  The plates were incubated at 37°C. After 18 hours, zones of inhibition (areas with no visible bacterial growth) were measured in three different directions for each disc. Unfortunately, the E.coli plates showed no inhibition. However, there was more activity against S. aureus and instances of collateral sensitivity and co-resistance could be observed in some strains (see graphs below). There were two extracts, made from F. lumbricalis and C. baccata that showed activity against all strains.


Antibiotic resistance versus seaweed susceptibility. Halo size in disc diffusion assay for 11 seaweed species on S. aureus strain sets consisting of susceptible and resistant strains. Error bars represent standard deviation.

All in all, this year has taught me that patience and inventiveness is key in life science. Also, ne upside of these mishaps was that I was forced to try and learn several basic molecular microbiology techniques. This will definitely be of great use to me in the future, especially during my final year dissertation project. I started this year as an undergrad with a general knowledge of medical science. However, my experience of the academic research environment was limited to lab practicals and one small scale attempt at a controlled trial. So I felt it was necessary for my development that I had a taste of what happened at the forefront of medical/life science. I came out of it a more mature professional, better versed in the scientific method and scientific communication. Also, being part of a vibrant research group allowed me meet several researchers from varying fields. More importantly, despite my many adversities I still have retained a strong interest in pursuing an academic research career but now with the added knowledge of the pitfalls this career direction entails. Finally, I would like to thank my supervisor Dr Michiel Vos for his guidance and patience, Dr Uli Klümper for tolerating my incessant advice seeking and everyone else in the lab for providing such a relaxed and welcoming atmosphere.

Michael Tadesse

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Re-post: Pitch: a Guide to the Bacteria and Archaea

The blog is a bit inactive at the moment and I hope to turn that around soon. In the mean time, I decided to re-post a blog entry from early last year to hopefully breath new life into this idea. I had been in touch with a publisher but the conditions were not right to pursue this book idea. hopefully there are other publishers or avenues available. Any comments are more than welcome in any case!



Background: inspired by a post by Jonathan Eisen on his blog ‘the tree of life’, I wrote a little post on ‘a Field Guide to the Bacteria’ last year. Both our posts were about the rather megalomaniacal (in a good way) idea of sampling, sequencing and identifying bacteria from the environment in ‘real time’. So rather than walking through the field with binoculars identifying birds, walking (anywhere) with a small sequencing device+computer and identifying microbes. This is obviously quite futuristic, but I have been thinking about a guide book to bacteria (from now on read ‘bacteria’ to mean both bacteria and archaea) that would be perfectly feasible. I think it is a very cool idea, but it would be great to have some of your feedback to see if it is actually worth pursuing. I am starting with the premise that a) bacteria cannot be identified in the field and b) a guide on bacteria cannot be in any way, shape or from be representative of actual diversity (in contrast to say most regional bird guides). More positively, I also think that c) bacteria can be beautifully illustrated and d) that they have very diverse and interesting life-styles that would make for some good reading. Applying a ‘traditional’ natural history format focusing on species diversity could be a very good way of bringing the sophistication of bacteria to the attention of the general public.

The pitch: a guide book where 100 bacterial species are represented by a page of text and an opposing page with a Scanning Electron Microscopy (SEM) picture. The format will be like any other guide book, utilizing pictograms to signify key characteristics (e.g. genome size, metabolism and habitat) and a short text segment on general biology as well as a segment on how the species impacts on us humans. Using 100 species would allow covering a lot of bacterial variation: many different taxonomic groups, many different habitats and niches and many different types of metabolism. Examples would include oceanic species, soil species, gut species, phyllosphere species, pathogenic species, hotspring species, food fermenting species, endosymbiotic species, photosynthesizing species, lithotrophic species, multicellular species, tiny species, ‘giant’ species, magnetic species, halophilic species, Bacteroidetes, Actinobacteria, Chloroflexi, etc etc. Each species would serve to highlight one specific, interesting behaviour.

The illustrations: beautiful SEM colour illustrations will be essential. Hands down the most beautiful SEM pictures of bacteria I have seen so far are those of award-winning ‘micronaut‘ Martin Oeggerli. Martin uses highly sophisticated post-processing colouring for an ‘acrylic finish’. See below for a fantastic image of a consortium of gut bacteria (including a plant fibre and the eukaryotic parasite Giardia on the far right):06-intestinal-bacteria-670

The format: there is some precedent: MicrobeWiki features illustrated descriptions of selected bacterial species (example page here). Although this is a great resource, it is not comparable to the coffee table book I have in mind. There is a case to be made to not produce a book, but build an app instead. This might be cheaper to do and also allow reaching a wider audience. Also, it will be relatively easy to add many more species to the app when the project is succesful. And it will allow linking to relevant websites, such as those hosting genome sequences etc (the downside to this is that the app needs curating to prevent dead links and just having a multi-FASTA file with millions of A’s and T’s and C’s and G’s pop up by itself is not that helpful to the average reader and would need a lot of extra context).  Of course, the two formats are not mutually exclusive. I still think a book is nicer though.

An example page: because a picture is worth a 1000 words, my sister Leonie helped me to produce an example page using my favourite bacterium Myxococcus xanthus. The SEM is by Juergen Berger at the MPI and was used a cover for Current Biology for one of my papers with Gregory Velicer (although beautiful, I think the colours are a bit artificial, soil is not blue!). I am not sure about the pictograms yet. Most conventional guides have a little map with a distribution range coloured in. I do not think that will be very helpful for most bacterial species, as they are generally very widely distributed and they definitely do not migrate (my thoughts on bacterial biogeography are summarized in this paper and this other paper). A pictogram of the habitat would be very useful however. Likewise, a pictogram summarizing genome information (genome size, chromosome and plasmid number and shape (circular or lineair) and number of genes) would be essential. More tricky but absolutely necessary would be a clear pictogram summarizing metabolism (and whether the species is aerobic or anaerobic). There are many other small interesting pieces of information that could be summarized in such a standard way. BOOK

The contributors: this will have to be a team effort. Here’s who would be needed:

  • the scientific community. PI’s that work on an interesting model system would be asked to a) write two pages on what is cool about their model system (+ provide a list of basic information needed to produce the pictograms) and b) send a sample to an SEM facility. In return they will have an outlet to educate the public about their favourite organism by being featured in a book and they will have permission to use a beautiful picture of their bug in their future talks. I know (of) many labs that I could ask to contribute and I do not see any problems there.
  • an SEM wizard. The production of SEMs and, as importantly, the post-processing of images would need to be done by a single person/facility to guarantee continuity and consistency. The quality of the images would be vital to the project.
  • an editor. That would be me. As with the images, the text needs to have a consistent format and style. Editing text provided by other scientists would be much less work than writing copy on 100 species myself from  scratch. I like writing; this should be doable.
  • a graphic designer. The book needs to look slick. The pictograms need to be informative and beautiful at the same time.
  • a  couple of expert microbiologists. Guides usually have a background section at the start featuring more general information about habitats, morphology and life history. This will be a must for this guide, as most readers will know comparatively little about the featured organisms. For instance, having an expert on metabolism on board to briefly explain this complicated topic to the lay person would make the guide much more valuable. The same goes for genome sequencing. Hopefully Jonathan Eisen would want to write the foreword.

How to get there: I am not sure! I guess there are three ways of securing money to make this happen: approaching publishers, crowdfunding and outreach grants. I do not have a good idea about the costs involved and the sales needed to cover them. I would greatly appreciate your comments on the book idea itself and about financing!


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