Medical Research Foundation funds £2.8M PhD programme in antimicrobial resistance

The Medical Research Foundation has announced a £2.8M PhD programme in antimicrobial resistance. Led by Matthew Avison at Bristol, this will bring 18 fully funded PhD students to support ongoing AMR projects. One of the students will be at Nottingham in association with the EVAL-FARMS project. We will be advertising three projects as part of the programme; these will be led by team members who don’t have any direct resource from the existing EVAL-FARMS funding – and are likely to be in the areas of phage-mediated spread of resistance, use of anaerobic digestion to mitigate resistance, and farm systems economic models to identify factors to best mitigate the impact of agri-AMR on human health.

Nottingham has also posted a Blog on the funding and I reproduce the text below:

New funding for Antimicrobial Resistance research

Research into new ways to tackle antimicrobial resistance has been given a boost as the University of Nottingham is one of the universities set to benefit from a £2.85m investment from the Medical Research Foundation.

New scientists will explore ways to tackle antimicrobial resistance through a new PhD training programme by the Medical Research Foundation, the charitable foundation of the Medical Research Council (MRC).

Fully funded

The first intake of the Antimicrobial Resistance PhD Training Programme will fully fund 18 students for four years, and the University of Nottingham is one of the 16 participating universities across the UK.

Dr Dov Stekel is leading the University of Nottingham programme and will be looking to recruit students later this year ready to start in 2018. Dr Stekel says: “This funding allows us to broaden our research with a PhD student working with team members who have not yet had access to resources from our other antimicrobial resistance research grants. Antimicrobial Resistance is a major global challenge and it will be very exciting to see the type of projects that are put forward and how they will help us progress our understanding of this problem.”

Antibiotics transformed healthcare in the 20^th Century and are considered one of the greatest medical achievements of the era. Today, we still rely on antibiotics to treat everything from minor cuts to life-threatening bacterial infections, and to prevent infection after surgery. These drugs have drastically improved our quality of life and increased our lifespan.

Global threat

In the 21st Century, antibiotic overuse and misuse has led to antibiotics rapidly becoming ineffective. Antimicrobial resistance, specifically antibiotic resistance, now poses a global threat to human life. We need urgent action to halt resistance and to speed up new treatments for bacterial infection. The Medical Research Foundations PhD Training Programme in AMR has been designed in response.

Working with the MRC, the Medical Research Foundation spotted a gap in funding for PhD studentships in this field of research – currently there are few emerging researchers trained in the multidisciplinary approach required to tackle the antimicrobial resistance problem. The programme is designed to help build a strong, active network of new researchers to approach this global challenge in innovative ways.

The Medical Research Foundation’s Chair, Professor Nicholas Lemoine, said: “The Medical Research Foundation is delighted to be funding the UK’s only national PhD Training Programme in antimicrobial resistance research.  We believe this will help to strengthen the UK’s research capacity to respond to the global health challenge of antimicrobial resistance, including antibiotic resistance and drug-resistant infections.”

The Medical Research Foundation is continuing to seek funds from its supporters and other sources to fund two further cohorts of PhD students in antimicrobial resistance in the future.

 

Sankalp Arya will be speaking at EDAR 4

Sankalp is on a roll! More good news. His Abstract to the 4^th International Symposium on the Environmental Dimension of Antibiotic Resistance has been accepted as an oral presentation. He’ll be giving a talk with title “Comparison of Different Modelling Approaches for Plasmid Transfer Dynamics” during Session 7 on Thursday 17th August. We have some interesting phage model results too so it is possible he may talk about both plasmid and phage mediated transfer.

When we submitted the abstract there was a “modelling” stream to submit to (which we dutifully did) – interestingly there is no modelling stream at the conference. There appear to be some bioinformatics talks, but it looks like Sankalp’s will be the only modelling talk. I am a bit surprised by this – there is a very clear need for models to be able to quantify spread of AMR, and make predictions about interventions. Perhaps on the other hand this is an opportunity for collaborations – we do modelling!

Congratulations again to Sankalp Arya

Congratulations again to Sankalp Arya for obtaining another scholarship. He has received a Travel Award to present his work at the 4^th International Symposium on the Environmental Dimension of Antibiotic Resistance (EDAR4). EDAR3 was fantastic – and EDAR4 will no doubt be much more widely attended. This is going to be a great opportunity for Sankalp to present his work (we are not yet sure whether this will be oral or poster) and hear from the best in the field.

 

Now recruiting: Research Associate/Fellow in Antimicrobial Resistance Modelling

We are now recruiting the mathematical modelling post-doc for the EVAL-FARMS project. This post will work with me, Theo Kypraios in Maths, and the EVAL-FARMS team more generally, developing mathematical models for risk of emergence of AMR pathogens in agricultural waste, using all the exciting data that are being generated by the empirical researchers on the grant. Details of the advert, as well as links to it, are:

Research Associate/Fellow in Antimicrobial Resistance Modelling

Agricultural & Environmental Sciences

Location:	Sutton Bonington
Salary:	£26,052 to £38,183 per annum, depending on skills and experience (minimum £29301 with relevant PhD). Salary progression beyond this scale is subject to performance
Closing Date:	Wednesday 28 June 2017
Reference:	SCI158617

We are seeking an excellent researcher in modelling of antimicrobial resistance. The successful applicant will use mathematical and statistical models to make predictions on risk of emergence of antimicrobial resistant pathogens in a farm slurry system and slurry amended soil. The post is funded by NERC-led EVAL-FARMS project (Evaluating the Threat of Antimicrobial Resistance in Agricultural Manures and Slurries). Thus the role holder will work closely with an interdisciplinary team, including experimental researchers in microbiology and analytical chemistry, and social researchers in science and technology studies, in order to develop meaningful, data driven risk models that could inform policy and practise. The work will involve deterministic and stochastic models, Bayesian statistics, data analysis and presentation.

Applicants must have, or be very close to completing, a PhD in mathematical, computer or statistical models applied to a relevant area in the biological or environmental sciences. Research experience in applying such models in antimicrobial resistance, metagenomics, analytical chemistry and/or water quality would be desirable. Applicants must be able to demonstrate skills in Bayesian approaches, including relevant computational techniques such as MCMC, development and analysis of deterministic and stochastic models, programming in a relevant language (e.g. R, Python or Matlab) and a broader appreciation of science. Applicants must also be able to demonstrate research ambition through timely publication of research, coupled with commitment to the research project as part of their on-going career development. Excellent oral and written English language skills are essential.

The post is a joint appointment between the Schools of Biosciences and Mathematical Sciences. The post holder will normally work on the Sutton Bonington Campus, and will also have meetings on the University Park Campus with staff in the School of Mathematics and other collaborating schools.

Fixed term for 2 years from 1st September 2017

Applications can be made through the University of Nottingham web site. I am happy to receive informal enquiries.

Congratulations to Sankalp Arya: International Research Collaboration Award

Congratulations to Sankalp who has received a £2300 International Research Collaboration Award from the University of Nottingham. Sankalp will spend two months (September and October) in Barth Smets’s laboratory at the Technical University of Denmark. This is a really fantastic opportunity for Sankalp to work in one of the leading environmental microbiology groups in the world. His work will focus on developing the iDynomics platform for individual based modelling of microbial interactions to model antimicrobial resistance. Well done Sankalp! And I look forward to visiting Barth’s lab too as part of the project.

 

Alan Perelson’s 70th Birthday Conference: Viral Dynamics: Past, Present and Future

Sankalp and I have just returned from a weekend trip to Santa Fe for the Viral Dynamics conference in honour of Alan Perelson’s 70th birthday.

The conference itself was very high quality – excellent talks throughout from some extremely eminent people in virus research. I particularly appreciated David Ho’s opening talk and Alan Perelson’s closing keynote; David’s talk on HIV dynamics reminding me just how good Alan and Avidan Neumann’s modelling contribution was: it wasn’t about developing big complex models, or doing very fancy mathematics; it was about doing the right simple model to make the most use of the data. Alan’s talk focussed on his earlier work in theoretical immunology – very many interesting examples showing how much you can learn by thinking in mathematical/computational ways.

The best part of the conference was meeting up with people – whether old friends from the short time I spent in LANL (Alan, Jack) and my PhD days (Ruy, Sebastian) – or brilliant people I hadn’t met before with whom I had some very stimulating conversations.

What was also evident was the warmth felt by so many people towards Alan. I only spent 3 months in the lab in 1994 – in between my degree and PhD – and went back for another month in the summer of 1995 – and yet when Ruy Ribeiro sent the invitation I immediately felt that this was a meeting I couldn’t miss. Many people there had collaborated with Alan for many years. And while Alan’s contribution to science is enormous, the plaque that the organizers made for him was for friendship, collaboration and mentorship, with a network graph of his collaborative research outputs. In this, Alan is a positive example for us all.

We went with a poster:

which was Sankalp’s first conference poster presentation! I thought that this would be a good opportunity for him; although Sankalp’s model is about bacteriophage in the context of AMR, while the conference focussed on human disease viruses, the conference attendees mainly worked in mathematical models of virus dynamics. This meant that Sankalp was among people who understood what he was doing and why he was doing it, speaking the same language. Sankalp was busy – he had people speaking with him for the full 2 hours of the poster session – and we received many interesting ideas and suggestions from these conversations.

Nearly new publication: Metal Resistance and Its Association With Antibiotic Resistance. Advances in Microbial Physiology

Last month the review that Sankalp and I contributed to was published on line by Advances in Microbial Physiology. This review was led by Jon Hobman, with considerable writing by Chandan Pal. It is a real honour to have co-authored with the amazing Joakim Larsson. My own contribution was small: Sankalp contributed some review material on modelling, and I got stuck in with Joakim and Jon in the editing phase to ensure we had a coherent story. Overall, this is a very nice and timely review, and we have had a lot of interest in it already. Citation and abstract:

Pal C, Asiani K, Arya S, Rensing C, Stekel DJ, Larsson DGJ and Hobman JL 2017. Metal Resistance and Its Association With Antibiotic Resistance. Advances in Microbial Physiology. DOI: https://doi.org/10.1016/bs.ampbs.2017.02.001.

Abstract

Antibiotic resistance is recognised as a major global threat to public health by the World Health Organization. Currently, several hundred thousand deaths yearly can be attributed to infections with antibiotic-resistant bacteria. The major driver for the development of antibiotic resistance is considered to be the use, misuse and overuse of antibiotics in humans and animals. Nonantibiotic compounds, such as antibacterial biocides and metals, may also contribute to the promotion of antibiotic resistance through co-selection. This may occur when resistance genes to both antibiotics and metals/biocides are co-located together in the same cell (co-resistance), or a single resistance mechanism (e.g. an efflux pump) confers resistance to both antibiotics and biocides/metals (cross-resistance), leading to co-selection of bacterial strains, or mobile genetic elements that they carry. Here, we review antimicrobial metal resistance in the context of the antibiotic resistance problem, discuss co-selection, and highlight critical knowledge gaps in our understanding.

First use of bioRxiv: Reconstructing Promoter Activity From Lux Bioluminescent Reporters

Today I have made a new publication foray and submitted a manuscript to bioRxiv. This is the main paper to have come out of work on our BBSRC Lux grant. We are yet to find a peer-review home – but one of our co-authors has already had a conversation with someone who wants to use the method – so it was time to put the manuscript out there while we continue with the peer-review process. R code and Biomodels submission will follow. The manuscript details are:

Mudassar Iqbal, Neil Doherty, Anna M L Page, Saara N A Qazi, Ishan Ajmera, Peter A Lund, Theodore Kypraios, David J Scott, Philip J Hill, Dov J Stekel 2017. Reconstructing Promoter Activity From Lux Bioluminescent Reporters. bioRxiv 117093; doi: https://doi.org/10.1101/11709. 

Abstract

The bacterial Lux system is used as a gene expression reporter. It is fast, sensitive and non-destructive, enabling high frequency measurements. Originally developed for bacterial cells, it has been adapted for eukaryotic cells, and can be used for whole cell biosensors, or in real time with live animals without the need for slaughter. However, correct interpretation of bioluminescent data is limited: the bioluminescence is different from gene expression because of nonlinear molecular and enzyme dynamics of the Lux system. We have developed a modelling approach that, for the first time, allows users of Lux assays to infer gene transcription levels from the light output. We show examples where a decrease in bioluminescence would be better interpreted as a switching off of the promoter, or where an increase in bioluminescence would be better interpreted as a longer period of gene expression. This approach could benefit all users of Lux technology.

Not stated in the abstract is that we have also discovered experimental evidence for product inhibition of the LuxAB reaction.

If you like the article, and would like to try the method, or give us feedback, please do be in touch.

Congratulations to Hannah Williams and Laurence Shaw

Congratulations to both Hannah Williams and Laurence Shaw who have both now left the lab (after short positions) to new roles. Hannah is now working at Public Health England as a mathematical modeller. Laurence is now working for Nottingham Trent University as a lecturer in statistics. Wishing both Hannah and Laurence all the best in what I am sure will be fabulous careers. Both are on fixed term contracts so if you are reading this and looking to recruit an excellent mathematician/statistician then both Hannah and Laurence have my highest recommendation!

On AMR Panel with Lord Jim O’Neill at University of Nottingham Chancellor’s Lecture

Last night I had the enormous privilege of being on a panel following Lord Jim O’Neill’s lecture on AMR as part of the University of Nottingham’s Chancellor’s Lecture series.

It was a real coup for the university to have Jim O’Neill speak. It was a great event – well attended by alumni and many other’s. The lecture was brilliant: O’Neill is a very engaging speaker and spoke with confidence and passion on the findings of his report. He mainly focussed on the ten point plan:

 

It was especially interesting seeing AMR from the perspective of an economist: not just in quantifying the problem in monetary terms (his argument that $40B spend will save $100T costs is compelling) but also how he breaks down the solutions into ‘supply’ and ‘demand’ side solutions and especially his emphasis on the importance of reducing demand for antibiotics through 6 of his points. (I’m not sure where our emphasis on waste management fits into that – but that is another matter – and actually having an economist (Steve Ramsden) on our project also helps framing it).

Professor Liz Sockett kindly asked me to serve on the panel (along side Dr Mat Diggle from EmPath) – this was a new experience for me – I was a little nervous – but the questions were good and interesting. The first couple of questions were more clinically focussed and answered by Liz and Mat. A question came up about how we prevent rapid spread of resistance to any new antibiotics we might discover. Mat gave a good answer from a clinical perspective, and I was able to add that there would need to be very wise use (if at all) of any new clinically important antibiotics in veterinary use. (To be fair, that point is  made in the O’Neill report anyway!) And then got a question direct to me about agricultural waste  management practises in developing countries. This was a nice one – as I have recently visited China and then had visitors from South Africa. So I was able to speak about the challenges of AMR from pig farming in China – the Chinese government are very committed to environmental research and China has a very well-funded research programme; South Africa is also very interesting because there is a mix of modern farming where the challenge of reducing antibiotic use is similar to in the UK, and then traditional subsistence farming, where nutrition is the biggest challenge, and the antibiotic challenge is more about access to antibiotics rather than use reduction.

After the talk, many interesting people came to speak with me, which was really nice, while Professor Christine Dodd looked after our stand and she also received many questions.

Official photographs will follow. The photograph at the top is thanks to Adam Roberts (from his twitter feed).