New paper: A model of antibiotic resistance genes accumulation through lifetime exposure from food intake and antibiotic treatmentNew paper:

Absolutely delighted that this paper is published in PLOS ONE.

Todman H, Arya S, Baker M, Stekel DJ (2023) A model of antibiotic resistance genes accumulation through lifetime exposure from food intake and antibiotic treatment. PLoS ONE 18(8): e0289941. https://doi.org/10.1371/journal.pone.0289941

Abstract

Antimicrobial resistant bacterial infections represent one of the most serious contemporary global healthcare crises. Acquisition and spread of resistant infections can occur through community, hospitals, food, water or endogenous bacteria. Global efforts to reduce resistance have typically focussed on antibiotic use, hygiene and sanitation and drug discovery. However, resistance in endogenous infections, e.g. many urinary tract infections, can result from life-long acquisition and persistence of resistance genes in commensal microbial flora of individual patients, which is not normally considered. Here, using individual based Monte Carlo models calibrated using antibiotic use data and human gut resistomes, we show that the long-term increase in resistance in human gut microbiomes can be substantially lowered by reducing exposure to resistance genes found food and water, alongside reduced medical antibiotic use. Reduced dietary exposure is especially important during patient antibiotic treatment because of increased selection for resistance gene retention; inappropriate use of antibiotics can be directly harmful to the patient being treated for the same reason. We conclude that a holistic approach to antimicrobial resistance that additionally incorporates food production and dietary considerations will be more effective in reducing resistant infections than a purely medical-based approach.

This article has also made National and International news, including The Times, The Telegraph, The Independent, the Evening Standard, the Telegraph and Argus, msn.com, and The National (UAE).

Antimicrobial resistance in dairy slurry tanks: a critical point for measurement and control

I am absolutely thrilled to report the publication of our most recent article, Antimicrobial resistance in dairy slurry tanks: a critical point for measurement and control, in Environment International. This is the uncorrect proof. This was a true team effort – 29 authors! – look at the list!

Michelle Baker, Alexander D Williams, Steven P.T. Hooton, Richard Helliwell, Elizabeth King, Thomas Dodsworth, Rosa Maria Baena-Nogueras, Andrew Warry, Catherine A. Ortori, Henry Todman, Charlotte J. Gray-Hammerton, Alexander C. W. Pritchard, Ethan Iles, Ryan Cook, Richard D. Emes, Michael A Jones, Theodore Kypraios, Helen West, David A Barrett, Stephen J Ramsden, Rachel L Gomes, Chris Hudson, Andrew D Millard, Sujatha Raman, Carol Morris, Christine E R Dodd, Jan-Ulrich Kreft, Jon L Hobman, Dov J Stekel.

https://doi.org/10.1016/j.envint.2022.107516

Abstract: Waste from dairy production is one of the largest sources of contamination from antimicrobial resistant bacteria (ARB) and genes (ARGs) in many parts of the world. However, studies to date do not provide necessary evidence to inform antimicrobial resistance (AMR) countermeasures. We undertook a detailed, interdisciplinary, longitudinal analysis of dairy slurry waste. The slurry contained a population of ARB and ARGs, with resistances to current, historical and never-used on-farm antibiotics; resistances were associated with Gram-negative and Gram-positive bacteria and mobile elements (ISEcp1, Tn916, Tn21-family transposons). Modelling and experimental work suggested that these populations are in dynamic equilibrium, with microbial death balanced by fresh input. Consequently, storing slurry without further waste input for at least 60 days was predicted to reduce ARB spread onto land, with >99% reduction in cephalosporin resistant Escherichia coli. The model also indicated that for farms with low antibiotic use, further reductions are unlikely to reduce AMR further. We conclude that the slurry tank is a critical point for measurement and control of AMR, and that actions to limit the spread of AMR from dairy waste should combine responsible antibiotic use, including low total quantity, avoidance of human critical antibiotics, and choosing antibiotics with shorter half-lives, coupled with appropriate slurry storage.

This is the culmination of more than 10 years of work: on 28th March 2012 I arranged a visit to our University Farm, which led to the key insight and idea behind this work. This article is a testament both to slow scholarship, and to deep interdisciplinarity. It really would not have been possible without all of the team we put together.

What if every graduand had a personal message at graduation?

A few weeks ago, our older daughter attended the Steiner School Olympics. All children in Year 6 (known in school as Class 5) from all Steiner schools in the country gathered together in the fields of one of the larger schools, to participate in Greek games – running, jumping, throwing and wrestling. It was a wonderful event, and, unlike ‘mainstream’ sports days, every child received a medal. For two days before the actual event, the children camped out, and practised the disciplines with various teachers, who observed them carefully. At the medal ceremony, as each child received their medal, the person giving the medal had a personal message for that child, based on their observations of that child, as well as those of other teachers. This message represented that child’s strengths, the specific challenges that they had overcome, and the particular journey they had travelled in participating in the games.

I have attended many university graduations. These are formal affairs, in which each student is called by name, shakes hand with the presiding officer on the stage, and leaves, normally to gather their certificate. What if each graduand received a personal message from their presiding officer? A message that reflected their personal journey, with contributions from personal tutor, project supervisor, and other staff (or students) associated with their learning journey or extra-curricular activities (sports, societies and so forth)?

The first consequence would be practical. A cheap objection to this idea is that it would make graduations too long. But this can be easily overcome; the Steiner Olympics delivered personal messages to each child by running twelve medal-givers in parallel, alongside speeches given to all children (and assembled parents). Graduations could also have parallel components as well as serial ones – and while that might make graduations a little less formal – that wouldn’t necessarily be a bad thing – and they needn’t be longer.

More profound, however, would be the collation of personal content for each individual student. This would require all sorts of staff and others to better get to know their students, reflect on their journeys, and work together to put together suitable words for that student to hear at their graduation. It would, quite simply, be transformative of the student experience. Instead of an increased obsession with impersonal analytics, gleaned from engagement (or otherwise) on various on-line learning platforms, or impersonal lists of marks, staff would have to construct a narrative of the student’s time at university based on their relationships with the students, and personal observations. Personal tutors would necessarily have to engage regularly with the student and with others to build this message. And graduations would be so much more personal and meaningful.

PhD opportunity: Artificial gene regulatory networks as a new AI paradigm

An opportunity to study for a fully funded PhD with Colin Johnson (Computer Science) and myself: Artificial gene regulatory networks as a new AI paradigm.

Gene regulatory networks (GRNs) are the primary ways by which living cells are programmed to respond to their environment in real time. They allow for a population of genetically identical cells to behave differently, for example the way the cells in our eyes behave differently from cells in our skin. GRNs evolve in a specific way, allowing them to learn new responses or behaviours from previous patterns without losing existing knowledge. Artificial GRNs (aGRNS), that is, computer implementations of GRNs, have been used to help understand the biology of GRNs. However, they have not been considered as a computational paradigm in their own right.

The aim of this project is to establish aGRNs as a computational AI paradigm. It will involve the implementation of aGRNs using both deterministic and stochastic formulations, and the identification and testing of problem types for which this paradigm is likely to be especially valuable. These include systems that need to switch rapidly between different contexts, and systems that need to transfer learning from one domain to another. These are both important challenges for improving the generalisation of AI systems.

Applicants are expected to have strong computer programming skills and a broad knowledge of artificial intelligence. Some biosciences background would also be beneficial to help understand the concepts, but this could be learned as part of the project if needed.

Full details of the scheme, including how to apply, as well as many other projects on the same scheme, can be found at:

https://www.nottingham.ac.uk/computerscience/studywithus/postgraduateresearch/nottinghamdtcinai.aspx

Antimicrobial resistance in dairy slurry tanks: a critical point for measurement and control: our interdisciplinary EVAL-FARMS paper is now on bioRxiv

I am absolutely delighted to say that the big interdisciplinary paper from our EVAL-FARMS project is now live on bioRxiv. (Many single discipline papers have already been published). This has taken a very long time to write – the most complex paper I have led with the greatest number of coauthors (29 authors) – and I think worth it in the end! It is actually 10 years from my first visit to the Dairy Centre and this paper coming out – which also emphasises the value of slow scholarship.

The link to the preprint is: https://www.biorxiv.org/content/10.1101/2022.02.22.481441v1

M Baker, AD Williams, SPT Hooton, R Helliwell, E King, T Dodsworth, RM Baena-Nogueras, A Warry, CA Ortori, H Todman, CJ Gray-Hammerton, ACW Pritchard, E Iles, R Cook, RD Emes, MA Jones, T Kypraios, H West, DA Barrett, SJ Ramsden, RL Gomes, C Hudson, AD Millard, S Raman, C Morris, CER Dodd, J-U Kreft, JL Hobman and DJ Stekel

Antimicrobial resistance in dairy slurry tanks: a critical point for measurement and control

Abstract

Waste from dairy production is one of the world’s largest sources of contamination from antimicrobial resistant bacteria (ARB) and genes (ARGs). However, studies to date do not provide necessary evidence to inform antimicrobial resistance (AMR) countermeasures. We undertook a detailed, interdisciplinary, longitudinal analysis of dairy slurry waste. The slurry contained a population of ARB and ARGs, with resistances to current, historical and never-used on-farm antibiotics; resistances were associated with Gram-negative and Gram-positive bacteria and mobile elements (ISEcp1, Tn916, Tn21-family transposons). Modelling and experimental work suggested that these populations are in dynamic equilibrium, with microbial death balanced by fresh input. Consequently, storing slurry without further waste input for at least 60 days was predicted to reduce ARB spread onto land, with >99% reduction in cephalosporin resistant Escherichia coli. The model also indicated that for farms with low antibiotic use, further reductions are unlikely to reduce AMR further. We conclude that the slurry tank is a critical point for prevalence and control of AMR, and that measures to limit the spread of AMR from dairy waste should combine responsible antibiotic use, including low total quantity, avoidance of human critical antibiotics, and choosing antibiotics with shorter half-lives, coupled with appropriate slurry storage.

Is Research Culture even the right phrase?

In my previous two posts, I have tried to express some of my views as to what makes a great research culture. But I am left wondering whether that is the right phrase – does the idea of great “research culture” capture what we are trying to build in our universities? On the surface it seems obvious – of course we want a great research culture! But is it limiting? What about our undergraduate and masters students – who supply the bulk of our funding? What about the way the university is run more broadly – and the culture among staff in administrative, professional, operational or facilities roles?

Start with our taught students. Our undergraduate and masters students operate within a broader academic culture. Sometimes they do research – as part of final year, summer, or masters dissertation projects – and in doing so may find themselves in research spaces (offices, labs, greenhouses, specialist libraries etc) or part of research teams. But mainly they don’t – interacting with teaching staff (who may or may not also be researchers) in formal spaces, and each other in spaces both formal and informal. What kind of culture do we foster among our undergraduates?

Obviously undergraduate life is and should be a broad experience – encompassing both academic and non-acadfemic activities – but at the same time we do want to foster an ‘academic culture’ among our students. As an undergraduate in a very traditional university, I have fond memories of the informal, peer-supported learning, as we worked on maths problems together, that was facilitated by the physical design of our student accommodation. One of my best memories was a midnight trip with fellow maths students to a local playground, where we investigated Coriolis and centripetal forces on the roundabout. Now, as a personal tutor, I have had tutor groups who would only talk about clubbing, and tutor groups who have talked about science. But the question isn’t so much either/or – students may well do both – the question is more something like this: if, as university leaders, we are trying to foster an atmosphere in which it is normal for students to have conversations or other shared experiences about academic matters, then is “research culture” the right phrase to describe what we are seeking, or are we seeking a more general “academic culture” that encompasses a way of being not only for our research staff and students, but also our teaching staff and students, accepting some degree of overlap in both categories? Or to put it another way, are there two separate enterprises associated with building a strong “research culture” among researchers, and a strong academic culture among taught students, or are are these two parts of the same goal?

Turning to broader aspects of academic culture. A current story: our university (like many others) is undertaking a review of its buildings, to ensure they meet the needs of staff and students as we return to campus “post” pandemic. The Researcher Academy (graduate school + support for research staff and supervisors; and on whose leadership team I serve) has a representative on this review committee – who is – amazingly – an (academic) architect. This of course makes sense – after all, this person is by far and away the most qualified of us to represent us in this review. This is also the very first time I have seen an academic’s expertise being used to support the running of the university. It really shouldn’t be radical – yet somehow it is exceedingly rare. In a counter-story, a couple of years ago we ran into potential trouble over possible breach of consumer protection law in changes to PhD project offers; when I suggested contacting a professor of consumer protection law (whom I happened to know) in our law school for some informal advice, this was seen as too radical to countenance. But why not? After all, this person (as with the architect) has the right expertise! I can go on. We have a world-leading nutrition department in our campus – but they have no input in the food served. We have world experts on organizational behaviour and industrial relations in our business school; are they called upon to support the running of the organization?

And it would be hubris to suggest that expertise exists only among academics, and not among professional or administrative staff. Recently, I have taken over a module in project management for our masters students. But while I have managed research projects, I am no expert in project management. So I have taken the (again radical, but shouldn’t be) step of finding a project manager in our Estates department to help me deliver this material who has the expertise an experience that I don’t have, which will benefit our students as we teach them.

Back to my key point. These stories all illustrate that we could be aiming for a broader “academic” culture – that respects and uses the collective expertise of the university in all its activities – including the way the institution is run – and not just research and/or teaching. Again, should the quest for this cultural orientation be seen as separate from the drive for an excellent research culture, or is it also bound up with it?

Defining or describing research culture: Concordat, REF and PRES

What is a great research culture? How do we build one in our universities? I first started thinking about it a couple of years ago – following some mixed feedback from PRES (Postgraduate Research student Experience Survey) on Research Culture. I have since run into it while writing our REF research Environment Statement, and it has come up again in my role as chair of the University’s Research Staff Committee as we look at the university’s implementation of the Concordat to Support the Career Development of Researchers. And now we have the latest PRES scores again – and again we are forced to look at research culture. These three exercises all take different views on research culture.

I find the Concordat’s position least satisfying. The Concordat places an ‘supportive and inclusive research culture’ as one of its aims. Within this, the institution (rightly) has obligations towards mental health and well-being, workloads, bullying, harassment, EDI, integrity – these are all very important, but for me they don’t speak to research culture. Such provisions should be in place in any employer or workplace – true, researchers need and deserve these, but so do teachers, bus drivers, hairdressers, doctors, builders and anyone else seeking to do their job and live with dignity. So we can, should, and will implement the Concordat, and any university will be the better for it, and it will be a better place to work, but not necessarily help us do great research.

The REF is really about research environment, although one might think this should intersect strongly with research culture. Our Environment Statement was long: 14,400 words, written to meet prescribed scoring criteria. But again, the REF requirements – while scoring many important factors – don’t really describe a research ‘culture’ as such. Yes, we need a research strategy; yes, we need strategies for recruitment, promotion, EDI, support of ECRs and so forth – and the evidence of their success – in terms of research grants or important papers. So too is it important to show that our research is well-funded, and to enumerate the fabulous research facilities we have, or to describe the influence our research has on the broader community outside of the university. But however important all these things are, they don’t really speak to research culture – one could have all these things and have a brilliant research culture – or the reverse – have an institution full of over-worked, exploited and miserable research staff and students.

Back to the PRES, it’s four questions about research culture seem, to my mind, to do a better job then Concordat or REF:

• I have access to a good seminar programme in my research area
• I have frequent opportunities to discuss my research with other researchers including research students
• The research community in my research area stimulates my work
• I am aware of opportunities to become involved in the wider research community, beyond my department

For me, an excellent researcher culture it is something about the collective and the individuals’ place in it – about the experience of doing research in an institution that is about a commitment to the furthering of knowledge together with others – a joy of doing research among other researchers – of sharing and discussing ideas in respectful and fruitful ways – an experience of success – insofar as having moments when you make a discovery and see the world differently from then on – and are empowered to share that with others, or to use that new knowledge to make a positive impact to people’s lives – and similarly, to see the world differently from learning about the discoveries of others, i.e. to both inspire and be inspired by others. PRES’s four questions capture much of this – even if the answers are reduced to Likert scale data. (The open question answers are often so much more informative). In contrast, the Concordat largely speaks to and about individuals – being supported in their workplace – but nothing about the collective. To some extent REF does this too, but from an institutional perspective: what are the structures and facilities that allow individual researchers to do well.

In summary – we need all of the matters addressed in all three instruments – they are all important – but it would nice to see the next incarnations of Concordat and REF learning a little from PRES in their description and definition of research culture.

What universities can learn from the House at Pooh Corner: the importance of play and of doing Nothing

Our younger daughter is currently into Winnie the Pooh so we have been reading the stories to her. The other night I read the very poignant final chapter of House at Pooh Corner; I had only ever read it as a child – this is my first time as an adult – and AA Milne beautifully writes about Christopher Robin’s immanent transition out of early childhood and its magical world. The animals know he is going to leave them soon. After explaining to Pooh that doing Nothing is his favourite thing, we get this dialogue:

“I’m not going to do Nothing any more.”

“Never again?”

“Well, not so much. They don’t let you.”

and a little later:

“Pooh, promise you won’t forget about me, ever. Not even when I’m a hundred.”

What has this got to do with universities? And research culture? Well, the importance of play, and the importance of doing Nothing. These are the source of our creativity, of our new insights, of our community building, of our connection with our (increasingly younger as we age) students, of the new ways we can inspire our students. They are central to our success.

The most impressive researchers I have ever met have in common their extreme playfulness. I have been fortunate enough to have known Ed Southern (inventor of Southern Blots and DNA microarrays; I worked for his company) moderately well – his playfulness in his approach to science was remarkable and infectious, and, without doubt, equally integral to his remarkable creativity and problem solving. I heard Donald Knuth (author of TeX) speak – just as playfully – as he showed a simulation of his co-routine code. “What I like about co-routines is not that they are especially useful, or especially efficient; it’s that the way they work together to solve problems is so /cool/.” I heard John Conway (co-author of the Atlas of Finite Groups and inventor of the Game of Life) speak – full of playfulness and love for mathematics and games – about his discovery of the Conway groups “when I realized what they were I lay on my college bed and kicked my arms and legs about like a baby.”

As for doing Nothing – I was fortunate enough to do my PhD at a very traditional university that, at least at the time, had all the right structures for the right sort of doing Nothing. Departmental coffee was at 11am and tea was at 4pm. These were cheap, in-sourced, low-cost, out of the hatch affairs, not the expensive outsourced branded outlets that are now popular. Everyone went. The most successful academics were regulars – and these were highly ambitious people with publication lists anyone would be proud of. Many then went to college lunch. These were all places for productive exchange of ideas. There was time for sports not just among students but staff; my PhD supervisor was often playing tennis or squash, while the professorial group head enjoyed regular games of croquet. All this doing Nothing didn’t prevent the flow of Nature and Science papers – quite the reverse – the conversations and the down-time were essential to get the creative juices flowing.

So I say to all of us – especially those of us in leadership roles in universities – embrace play and doing Nothing. They are crucial not just for our physical and mental well-being, and not just for our capabilities to connect with our students, but also for our being able to be successful in producing high quality and ground breaking research.

Welcome to Anastasia Kadochnikova and Shu Liang

This summer we welcome two new members of the lab. Anastasia Kadochnikova has joined us as a PostDoc on the UK-Argentina AMR grant led by Helen West. Shu Liang has joined us on a UK-Adelaide joint PhD programme, supervised here by myself and Alex Burgess, and in Adelaide by Volker Hessel and Matthew Knowling.

Anastasia writes:

I recently joined Dov’s lab as a Research Fellow and will be working on the UK-Argentina AMR grant led by Dr Helen West. My research will focus on spatio-temporal modelling of the AMR dynamics in poultry manure heaps. The principal aim of this modelling work is to quantify the hypothesis that the heat transfer inside heaps may create favourable conditions for the survival of AMR bacterial populations. The developed model will then be calibrated against experimental data collected by our collaborators in the UK and Argentina. 

Before joining the University of Nottingham, I worked as a Research Associate at the Department of Automatic Control and Systems Engineering, The University of Sheffield. As part of the EPSRC-funded project SYSDYMATS, I developed nonlinear system identification frameworks to aid the process of data-driven design of auxetic materials. I obtained a PhD in Systems Engineering from the same department in 2019. My doctorate, supervised by Prof Visakan Kadirkamanathan, focused on modelling and identification of the immune cell migration during the inflammatory response in transgenic zebrafish. Prior to starting my PhD, I completed an Engineering degree from Moscow Aviation Institute in 2015, specialising in mathematical modelling of complex engineered systems. An Engineering specialist degree in Russian Federation is equivalent to an MEng degree in the UK. 

My research interests lie in the areas of dynamical modelling and system identification. I enjoy working on interdisciplinary projects as they provide me insight into various applications and industries while broadening my core expertise in model design and statistical inference. However, interdisciplinary collaboration is still facing many challenges. Although we observe an increase in use of mathematical modelling as a tool for data interpretation and hypothesis testing, one of the biggest problems today is finding effective ways to translate modelling outcomes into changes in existing practices and regulations. The AMR project particularly appealed to me because it aims to utilise predictive modelling to inform policy and to improve farming practices, which will have both societal and environmental impact.

Outside of work, I enjoy learning languages and reading speculative fiction. Currently I am learning Spanish. I am also a casual runner and an occasional but lazy hiker.

Shu writes:

I am a PhD student in a joint project between the University of Nottingham and the University of Adelaide. This project addresses the design of a closed loop agriculture system for space, which is

motivated by the need to create human life support facilities for future planetary

exploration. Before pursuing my Ph.D., I obtained a master’s degree in chemical engineering from the University of Adelaide. The main research project is the use of recycled grease trap waste as a raw material to catalyze the synthesis of biodiesel by immobilized lipase in a microreactor.

Covid vaccine – a triumph for the natural sciences – a challenge for the social sciences

Today I received my first dose of the Covid-19 vaccine. I am of course delighted, both for myself, and that this act protects others – vaccination is a public health practice – even an imperfect vaccine works because if enough people are vaccinated, we protect each other.

The rapid production of vaccines to Covid-19 is a scientific success story of unprecedented and historic proportions. It is the culmination of decades of investment in science and science education in countries across the world; these have led to our knowledge of virology and immunology, the capability to visualize the virus (and ‘see’ spike proteins), to rapidly sequence its DNA, to understand its proteins and their structure, to develop recombinant vaccine vectors, and recombinant cell lines to produce them, all underpinned by an understanding of the fundamentals of molecular biology and genetics. And then our universities, hospitals, pharmaceutical and biotechnology companies employ large numbers of PhD-qualified scientists, who have been able to make these break-throughs – whose training and expertise results also from decades of investment in university research and PhD studentships. It has also benefited from unprecedented levels of knowledge sharing: DNA sequence databases have allowed us to access viral strain data, from the first strain sequence uploaded by Chinese scientists, to the large numbers of variant strains enabling us to track mutants; while preprint servers – a more recent phenomenon – have allowed rapid dissemination of research results not possible in the days of only printed journals. If ever there was an argument for continued investment in research infrastructure, including both pure and applied research, and especially in the training of research scientists through scholarships for Masters and PhD study, this is it!

And yet our societies now face a greater challenge – and a much harder one – the social, economic, political and educational challenge of ensuring that we vaccinate enough people in the world to protect everyone in the world? The natural sciences, where I work, don’t have these answers – these are questions for social sciences. (How ironic that the social sciences are often referred to as ‘soft’ when the problems they address are so hard). We are beset by inequalities across the world – we who are fortunate enough to live in the UK have access to vaccinations – but many people in many countries do not – how do we resolve this? And we are beset by inequalities within our societies – how do we ensure that our vaccines reach everyone – especially those communities who, while most impacted by the epidemic, might also be most hesitant to trust in the vaccines? How do we counter those voices who diminish the epidemic, belittle public health efforts or speak up against the vaccine – people who use their power or privilege to spread these lethal messages, or who provide the platforms (whether traditional or social media) that allow for their broad dissemination, without suppressing dissent? How do we educate our broader publics to be able to understand complex scientific ideas, or complex social ideas, or how to critique nonsense and the peddlers of nonsense? We do not yet have the societal structures that can answer these questions – I can only hope that as we emerge from this epidemic we are able to work towards breakthroughs in our social infrastructure that will exceed the scientific breakthough that led to these vaccines.