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:

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.

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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:

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.

oneillpanel

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:

 

10-point-plan_white

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).

 

 

 

 

Job Opportunity – Research Technician for EVAL-FARMS project

We are advertising for the second research technician post for the EVAL-FARMS project. The post-holder will be responsible for sampling from the slurry tank, with a particular focus on measuring water quality and preparation of samples for pharmaceutical analysis. The post-holder will work very closely with other team members.

Research Technician

Reference
SCI307616X1
Closing Date
Monday, 6th February 2017
Job Type
Technical Services
Department
School of Biosciences – Technical Services
Salary
£22494 to £26829 per annum, depending on skills and experience. Salary progression beyond this scale is subject to performance

Applications are invited for the above full-time post 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 wastewater slurry and soil samples & sample processing for water quality parameters and sample preparation/wet chemistry ready for LC-MS and ICP/AAS analysis. The role will require working off-site.

Duties will include:

  • Processing samples for water quality indicators (e.g. DO, TSS, COD, TOC) including spectrophotometer use.
  • Sample preparation of environmental samples for antibiotic drugs and metals suitable for LC-MS and ICP/AAS analysis.
  • 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 proven technical and/or experimental expertise in techniques for characterising environmental samples for water quality parameters e.g. DO, TSS, TDS, COD, TOC etc.

This full-time post is 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.

Risks and remedies for effective multidisciplinary research

Following my post about authorship networks, and the award of our multi-disciplinary AMR grant, I would like to share my thoughts on the structural risks of academic life to multidisciplinary research and some possible remedies.

Multidisciplinary research is of paramount importance. Many ‘big’ questions require a multidisciplinary approach: How to stop the spread of antimicrobial resistance? How to defeat cancer? How to measure gravity waves? How to land people on Mars?

Specifically, I will look at individualizing factors that  reward (or punish) academics or researchers as individuals rather than working together in multidisciplinary teams. Interestingly, these factors arise both from the traditional ‘scholarship’ model of academic life, and the modern ‘corporate/managerial’ model. For universities to best support multidisciplinary research it will require new thinking that both departs from the current managerial model, but also doesn’t go backwards to the traditional model.

Briefly, the individualizing factors from the traditional academic model are: the cult of individual brilliance; linear lists of research authors on publications; and research grants allowing only one PI. The individualizing factors from corporate university management are: individualized REF returns; workload planning models; performance targets; and strategic compulsory redundancies. And in the intersection between the traditional and corporate model: promotion. In detail then, each challenge followed by possible remedies:

Cult of individual brilliance. As academics, and as a society more generally, we are obsessed with the idea of brilliant individuals. Historically, ‘big’ research could be done by brilliant individuals. Charles Darwin, so we are told, got on a boat, looked at the birds in the Galapagos and came up with the theory of evolution. A similar story is told about  Einstein, trains and relativity. Sometimes we accept a great collaboration. Hardy and Ramanujan. Crick and Watson. Even among ‘normal’ (i.e. not world-changing) academics, humanities researchers speak of the ‘lone scholar’ while molecular biologists used to say ‘one grant, one post-doc, one protein’.  But actually these stories unravel. Take for example Crick and Watson. Most people now know that Rosalind Franklin played a pivital role in discovering the structure of DNA, and careful reading of the story reveal many other people who made critical contributions (e.g. Erwin Chargaff or Alec Stokes). Obsessions with big prizes do not help help: that Crick, Watsom and Wilkins got a big prize masks the fact that the discovery of the structure of DNA involved many contributions from many people.

How do we counter the obsession with individual brilliance? I think in truth almost all of us recognize that our work is not truly ‘our own’. We are all inspired by our teachers, our peers, our students, the people who wrote the brilliant paper we secretly wish we had written ourselves, or the people who wrote the mediocre paper who push us to do a better job. As long as we remember this, stop talking about big name prizes, and remove from our discourse the idea that ‘one person’ made some discovery – we can move forward. Importantly, we can have a big influence over the next generation in the way we teach. We have the opportunity to show to our students that the ‘big discoveries’ were mostly made by an interconnected collection of collaborators and rivals sharing ideas and being inspired by each other, not one or two heroes.

Linear lists of authors. This is a harder one to fix. Our research articles have a list of authors, and when we cite them, we typically only name the first on the list. Different fields have different conventions: some fields simply order from first to last in order of “importance of contribution”. In many sciences, the people who did the work get listed from the front, while the supervisors get listed from the back, so that first and last author have special prominence. In some fields authors are listed alphabetically. The problem with the normal convention in science is that hierarchies are established which give special prominence to two authors. How do you produce a fair author list for a complex, multidisciplinary study, where the findings reported result from genuinine collaboration between (say) three different laboratories?

So far, two main solutions have been employed. The first is to have joint first (or last) authorship. This works reasonably well insofar as a second author can indicate that their contribution is equal to the first. But it still suffers from the fact that one author is still listed first. The second solution has been to list author contributions. I remember when the idea was first touted it was said that a paper’s authors would become more like film credits than a linear list. But, rather than give informative detail, this has turned into a box-ticking excercise, with the contributions relegated to the bottom of the article.

In my previous post, I suggested a network view of authorship and contributions, rather than a linear list. To my mind, this solves many of the problems above. I received a number of questions about how the paper could be cited, and how credit would be quantified. To answer these, perhaps the network view could be enhanced in two ways. One possibility is to combine it with an alphabetic author list, so that there is no longer any hierarchy in that list. The second possibility – and I am not sure if I am sold on this – could be to (optionally) include a percentage contribution for each of the authors. This could satisfy the needs of those involved in bean-counting exercises (e.g. the REF).

Research grants allowing only one PI. Some grant organizations, for example RCUK, only allow a single PI on a grant. This means that where two or three people contribute equally to an application, their contributions cannot be equitably recognized. This situation is so easily remedied. The Wellcome Trust, for example, allows ‘Investigator Awards’ with two equal collaborators. Even the RCUK situation is inconsistent: two people from two different institutions can both be recognized as PIs, while if they were in the same institution one would have to be a co-I. We can call on all granting bodies to allow research grants to have more than one PI, listed as co-PIs, with joint and several responsibility for its delivery.

Individualized REF returns. For those outside British academia, you might be unaware of the REF (Research Excellence Framework): a process to apportion money between universities. University departments are assessed on the basis of their outputs (e.g. research papers that have already been peer reviewed and published) and then ranked. The REF can be criticized on many fronts; the problem with regards individualization is that departments need to decide which individual researchers to ‘submit’ to the REF and which not. Researchers submitted list their top four papers which are then given a number of ‘stars’ between 0 and 4. So with multidisciplinary papers from authors in the same department, this creates tension as to who ‘gets’ the papers for their REF return. And the stakes are high – an academic’s job is at risk if they are not submitted. Serious problem if two or three people in a department do their best work together and publish together.

Again, the remedy is simple. There is no need to individualize the return. The recent Stern review of the REF has suggested that different individuals in a department could return more or fewer papers – but it doesn’t go far enough! It would be just as easy to alter the REF so that university departments return their best papers – and these might be single or multi-disciplinary, involve one lab, two labs or many.

Workload planning models. Many universities in the UK are now implementing some kind of model of what work academics are doing, with points allocated for teaching, research and administrative duties. While on the one hand it is reasonable that tasks are shared in some equitable way, and on the other there is much to criticize about both the principle and practise of such models, here I will focus on the risks to multidisciplinary research that arise from individualization. Workload planning models are intrinsically individualizing. Each of us now has a ‘number’ on our heads – a proportion of a notional “100%” that we are supposed to be working – with risks of being too high (insufficient time for research) or too low (at best receiving an overload of tasks; at worst, redundancy). The problem is that we are judged as individuals – and need to ‘game’ the system as individuals.

Universities are complex, flat, structures, and a great deal of their success rely on acts of good will between colleagues (academic, technical and professional service). Historically, as academic staff, we are regularly doing favours for each other: standing in for tutorials, assessing and examing students, commenting on drafts of papers or grant applications and so forth. With the introduction of formal workload planning points, people start only doing those things that they get ‘points’ for. The helpful culture of saying ‘yes’ to your colleagues is at risk of being replaced with a culture of saying ‘no’.

Somewhere, somehow, these need to be pushed back against, so that we foster a collaborative environment. In the end, I think we need to argue against them for their weaknesses: it is impossible to compare teaching loads, research activity, administrative or leadership roles in a single system. Equity in teaching needs to be achieved through simpler measures of contact hours, not by risking collaborative environments through flawed metrics.

Performance targets don’t have to be individualizing but unfortunately frequently are. I am no fan of performance targets – but rather than critisize them outright, I will say here that where individuals are being told to be the PI on grants, or the lead author on papers, and that being a coI or middle author are being given less or no value, this will count against people carrying out collaborative work. There are many people, particularly those who have technology focussed laboratories (e.g. bioinformatics or mass spectrometry), who make very natural coIs on many grants – and that needs to be recognized and rewarded up to the highest levels. If there have to be performance targets at all, then at least these need to recognize collaborative working.

Strategic compulsory redundancies. There is nothing more individualizing than knowing that your job is on the line, and that you will be competing with your colleagues for a smaller number of jobs as part of a restructuring activity. I refer to ‘strategic’ redundancies as being a choice by the institution to cut jobs rather than to cut costs in other ways, e.g. infrastructure spend. (I contrast this with essential redundancies where the instutition as a whole is at risk and all spend is cut). Many institutions, even in the region where I live, have indulged in strategic redundancies. It is a disaster for multidisciplinary working if people are genuinely fearful about whether or not they will keep their jobs.

Quite simply, universities who wish to support multidisciplinary working should not indulge in strategic redundancies. This is a message the senior leadership teams need to hear and understand.

Promotion is probably the hardest of all to crack. Promotion is individual, whether seen through the traditional or managerial lens. Two people work very closely together on collaborative projects, and really neither would be able to be as successful in their research without the other. Could/should they be promoted together? (It is difficult to see how that might be implemented in any fair way). Can supporting the success of a colleague in of itself be part of a criterion for promotion?

On a different note, what about the technology-focussed academic I mentioned earlier (e.g. the bioinformatician or mass spectrometrist) who is coI on many grants, essential to many projects about the university, but rarely PI? Can this person be promoted on the basis of excellent collaborative venture? In order to support multidisciplinary research, universities need to recognize these types of contribution, and facilitate promotion to the highest levels on the basis of excellent collaborative, inter-disciplinary research.

The points I wish to make are not about any specific institution, but sector-wide. In the end, if we are to deliver on solving the big research questions, we need all of our employers to develop and foster environments that support and reward multidisciplinary research.