New publication: microbial mass movements

Delighted that our perspective in Science has been published.

Zhu Y-G, Gillings M, Simonet P, Stekel DJ, Banwart S and Penuelas J. Microbial mass movements. Science 357: 1099-1100.

My involvement is relatively minor: we have written a much longer piece (which we are looking to publish also) to which I have contributed a fairly substantial section on modelling – and then when Michael Gillings put together this short perspective for Science, he compressed everything I wrote into a single sentence! Maybe it is an improvement 🙂 Anyway, it is a real privelege to have coauthored which such amazing international scientists, and a delight that we have had it published in such a great journal.

Summary

For several billion years, microorganisms and the genes they carry have mainly been moved by physical forces such as air and water currents. These forces generated biogeographic patterns for microorganisms that are similar to those of animals and plants (1). In the past 100 years, humans have changed these dynamics by transporting large numbers of cells to new locations through waste disposal, tourism, and global transport and by modifying selection pressures at those locations. As a consequence, we are in the midst of a substantial alteration to microbial biogeography. This has the potential to change ecosystem services and biogeochemistry in unpredictable ways.

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Research Technician (2 Posts – 1 Full-time & 1 Part-time)

We are now recruiting for two technician positions for the EVAL-FARMS project.

Reference
SCI307616
Closing Date
Friday, 28th October 2016
Job Type
Technical Services
Department
School of Biosciences – Technical Services
Salary
ÂŁ22249 to ÂŁ26537 per annum (pro rata if applicable), depending on skills and experience. Salary progression beyond this scale is subject to performance

Applications are invited for the above full-time and part-time posts which are based within the School of Biosciences at the Sutton Bonington Campus.

The post is to provide technical support on a NERC funded research project “Evaluating the Threat of Antimicrobial Resistance in Agricultural Manures and Slurries”.

The role holder will assist with the collection of soil & slurry samples & processing the samples for microbiological, genomic, wet chemistry & water quality indicators and will require working off-site.

Duties will include:

  • Processing samples for further analysis by LC-MS, ICP/AAS, PCR and microbiological analysis and culture,general microbiological analysis & culture at ACDP 2,assessing water quality indicators using UV vis spectrophotometer
  • Ensuring stocks & equipment in own areas of responsibility are maintained & available for use.
  • Maintaining a safe working environment in accordance with statutory & University Health & Safety procedures.

Full details can be found in the job description.

Candidates must have a HNC in a relevant subject or equivalent qualifications plus considerable relevant technical/scientific experience OR substantial work experience in a relevant technical or scientific role.

Candidates should have experience of working with ACDP 2 pathogens and proven technical and/or experimental expertise in techniques for water quality analysis including filtration, COD analysis, molecular biology & PCR technologies.

These posts are available as soon as possible on a fixed-term contract for a period of 15 months.

Informal enquiries may be addressed to: Dov Stekel tel: 0115 9516294 Or email dov.stekel@nottingham.ac.uk. Please note that applications sent directly to this email address will not be accepted.

The University of Nottingham is an equal opportunities employer and welcomes applications from all sections of the community.

PhD opportunity: Tunable zinc responsive bacterial promoters for controlled gene expression

 

Tunable zinc responsive bacterial promoters for controlled gene expression

Supervisory Team: Dr Jon Hobman (School of Biosciences), Dr Phil Hill (School of Biosciences), Dr Dov Stekel (School of Biosciences).

Applications are invited for this 4-year PhD project which is part of a University-funded Doctoral Training Programme (DTP) in Synthetic Biology and associated with Nottingham’s new BBSRC/EPSRC Synthetic Biology Research Centre. Students will benefit from a diverse range of training opportunities, including specialist workshops, lectures and seminars, as well as participation in Nottingham’s yearly BBSRC DTP Spring School event.

Zinc is an essential metal, required in ~30% of bacterial proteins, but is toxic at higher intracellular concentrations. Bacteria such as E. coli have evolved sophisticated zinc import and export systems controlled by transcription factors that repress the expression of genes encoding importer proteins (regulator Zur) or activate expression of zinc efflux (regulator ZntR). These regulators and the promoters they control represent a good example of fine tuning of cellular response to external zinc concentrations (1) and different Zur and ZntR regulated promoters have different affinities and transcription levels. The aim of this PhD will be to study the levels of expression from engineered Zur and ZntR regulated promoters in response to zinc, so that a suite of promoters can be used to finely control gene expression in response to zinc levels in growth media. These promoters will be used to control gene expression in engineered bacteria using cheap zinc inducers and zinc chelators, and will allow tuned expression of industrially useful synthetic pathways in E. coli and other Gram-negative bacteria. These tunable promoters could have potential impact in a range of biotechnology/biosynthesis contexts.

The project is available from 1st October 2016 and is open to UK and EU students with a 2(i) degree or above in microbiology, genetics, biochemistry, or a related discipline. The work will be based at the School of Biosciences in Nottingham.

The supervision team for this project is multi-disciplinary, enabling training in a wide-range of subjects and techniques in microbiology, molecular biology, cell engineering, reporter gene systems, mathematical modelling, data analysis, and cell metabolism.

Applicants should submit a covering letter, CV and the names of two academic referees addressed to: Rob Johnston School Administrator Robert.Johnston@nottingham.ac.uk

Closing date for applications: 31st July 2016

Informal enquiries to Dr Jon Hobman ( Jon.Hobman@nottingham.co.uk )

(1)       Takahashi et al (2015). Journal of the Royal Society Interface 12: 20150069

 

Welcome to Joana Falcao Salles

We are delighted to welcome Joana Falcao Salles from the University of Groningen as a visiting fellow for this week. Joana’s visit has been funded by the EPSRC Bridging the Gaps AMR award held by the university. Joana will be giving two talks:

Today, Tuesday 22nd March 1pm Lecture Block A03, Sutton Bonington

Tomorrow, Wednesday 23rd March, 3pm, Trent B65, University Park

Title: Causes and consequences of soil microbial diversity

Abstract:

Soil microbial communities are extremely diverse, with values ranging from 1000 to 1000000 unique taxa per gram of soil. These communities of overwhelming diversity are responsible for the provision of many ecosystem services. Yet, our understanding of the mechanisms controlling this sheer microbial diversity and whether changes in microbial diversity influence ecosystem functioning is limited.
 
 In the first part of my talk I will discuss how we are using soil primary and secondary succession to understand the mechanisms leading to the establishment of soil microbial communities – the causes of microbial diversity. The focus here will be on a recently developed a framework that unravels the trajectories of microbial communities through succession along a stochastic/deterministic continuum. Collectively, this study gives a fundamental contribution to the understanding and predictability of microbial community assembly and succession.
 
The second part of my talk will focus on a key paradigm in microbial ecology, which is unravelling how soil microbial diversity drives ecosystem functioning – the consequences of microbial diversity. By focusing on two functions, denitrification and invasion resistance, I will demonstrate that soil microbial communities follow the expected biodiversity-ecosystem functioning relationships, i.e. that more diverse systems perform better than less diverse ones. Importantly, by using the concept of community niche, we provide evidence that efficiency in resource use – via resource complementarity and partitioning among resident species – is the overarching mechanism promoting the positive effects of diversity.
 
Overall, in a time where global change is a reality and biodiversity loss is expected to accelerate, understanding the mechanisms controlling the diversity of soil microorganisms is crucial to predict the responses of microbial driven process to global change scenarios and to sustain soil ecosystem services.

New publication: Mathematical modelling of antimicrobial resistance in agricultural waste highlights importance of gene transfer rate

We are delighted that our second paper – and first modelling paper – on antimicrobial resistance in slurry has been pubished, also in FEMS Microbial Ecology.

Baker M, Hobman JL, Dodd CER, Ramsden SJ and Stekel DJ (2016). Mathematical modelling of antimicrobial resistance in agricultural waste highlights importance of gene transfer rate. FEMS Microbial Ecology DOI:10.1093/femsec/fiw040.

The work came from the very short post that Michelle spent with us – funded by pump prime money from the school. Both the experimental paper (led by Jon Hobman) and the modelling paper have been accepted for the Virtual Issue of FEMS Microbial Ecology: Environmental Dimension of Antibiotic Resistance associated with the EDAR 2015 conference we attended last year. These papers can show the value and importance of timely institutional pump prime support.

Abstract

Antimicrobial resistance is of global concern. Most antimicrobial use is in agriculture; manures and slurry are especially important because they contain a mix of bacteria, including potential pathogens, antimicrobial resistance genes and antimicrobials. In many countries, manures and slurry are stored, especially over winter, before spreading onto fields as organic fertilizer. Thus these are a potential location for gene exchange and selection for resistance. We develop and analyze a mathematical model to quantify the spread of antimicrobial resistance in stored agricultural waste. We use parameters from a slurry tank on a UK dairy farm as an exemplar. We show that the spread of resistance depends in a subtle way on the rates of gene transfer and antibiotic inflow. If the gene transfer rate is high, then its reduction controls resistance, while cutting antibiotic inflow has little impact. If the gene transfer rate is low, then reducing antibiotic inflow controls resistance. Reducing length of storage can also control spread of resistance. Bacterial growth rate, fitness costs of carrying antimicrobial resistance and proportion of resistant bacteria in animal faeces have little impact on spread of resistance. Therefore effective treatment strategies depend critically on knowledge of gene transfer rates.

New publication: The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress

I am absolutely delighted to see the (online) publication today of our paper:

Takahashi H, Oshima T, Hobman JL, Doherty N, Clayton SR, Iqbal M, Hill PJ, Tobe T, Ogasawara N, Kanaya S and Stekel DJ 2015. The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress. Journal of the Royal Society Interface DOI: .

The abstract is at the bottom of the post. First I want to say why I am so happy about this particular paper.

1. This is the first piece of work I have published in which I have made a successful funding application (I say “I” loosely, as Taku Oshima wrote the Japanese part of the bid along with Naotake Ogasawara, Shigehiko Kanaya and Toru Tobe, and Jon Hobman wrote much of the UK part of the bid; however, I was PI as this was a Systems Biology call); led the research (most of the hard work was done by Hiroki Takahashi and Taku Oshima); wrote the paper (different parts were written by different people – almost all authors made an important contribution); and have seen the paper published. A complete cycle of more than 5 years from grant application to publication.

2. This is the first paper on which I am corresponding author that contains new experimental results. More than that, I played an important role in devising many of the experiments (time courses and viable cell count assays) – not in terms of technical details (in which I have little expertise) but in terms of what experiments we need and why we need to do them.

3. This is the first time I have come a complete “Systems Biology” cycle: from experiments, to models, to predictions, to experimental confirmation, to a new model and then new predictions.

4. Some of the most important ideas in this paper came as a result of one of the most enjoyable weeks in my scientific career. Hiroki, Jon, Selina and I were all attending the Biometals Conference in Brussels in July 2012. While Hiroki and I attended a few sessions of the conference, most of the time we spent in our hotel lobby trying to get the model to fit the data. The first data we had were the LB data, which the model could fit without too much trouble. When Taku asked me what other data we needed, I said: “time series, with different concentrations of zinc”, and by the conference we had those data too. Only one problem: the model no longer fitted the data.

Hiroki and I spent that week trying to work out how to get the model to work. Each morning, we sat in the hotel lobby, and over endless cups of tea, we devised new versions of the model; each afternoon Hiroki would code them up, and then run them overnight on the supercomputer in Japan. And the next morning, the model would still not fit the data. By the last day we were tearing our hair out: nothing we could think of would work. We had one last (desperate) idea: ditch the 100uM zinc data. Boom! The model fitted the 12.5uM zinc data just fine! And this led to the heterogeneity hypothesis, the viable cell count assay, the stochastic model, and all the results that make this paper exciting. It is that kind of week that we go into careers in science for: the frustration and delight of grappling with and overcoming a difficult problem.

5. As alluded to in the previous points, it has been an absolute delight working with my coauthors on this paper, and I have many happy memories in the UK, Japan and Brussels.

6. Finally, on a more personal note: we received this funding on 17th March 2010. In between receiving the funding and having the paper published (5 years later) I have got married (July 2010), had a baby (July 2011), had another baby (November 2013) and am now more tired yet more happy than at any other point in my life 🙂

Now for the abstract!

Abstract

Zinc is essential for life, but toxic in excess. Thus all cells must control their internal zinc concentration. We used a systems approach, alternating rounds of experiments and models, to further elucidate the zinc control systems in Escherichia coli. We measured the response to zinc of the main specific zinc import and export systems in the wild-type, and a series of deletion mutant strains. We interpreted these data with a detailed mathematical model and Bayesian model fitting routines. There are three key findings: first, that alternate, non-inducible importers and exporters are important. Second, that an internal zinc reservoir is essential for maintaining the internal zinc concentration. Third, our data fitting led us to propose that the cells mount a heterogeneous response to zinc: some respond effectively, while others die or stop growing. In a further round of experiments, we demonstrated lower viable cell counts in the mutant strain tested exposed to excess zinc, consistent with this hypothesis. A stochastic model simulation demonstrated considerable fluctuations in the cellular levels of the ZntA exporter protein, reinforcing this proposal. We hypothesize that maintaining population heterogeneity could be a bet-hedging response allowing a population of cells to survive in varied and fluctuating environments.