University policy: evidence and evaluation

The ICaMBlog this week features an article from Professor Bernard Connolly. Bernard is retiring today (March 31st 2016) and so we asked him if he could write a post on ‘anything he wanted’. Here Bernard discusses his frustrations with the frequent lack of evidence based policy making in universities.

Prof ConnollyI began my academic career as an undergraduate student at Sheffield University in 1973, I finish as the Professor of Biochemistry at Newcastle in 2016. Possibly the biggest change to have occurred over this forty or so years is the degree of surveillance and monitoring to which everybody at the University is subject. During my undergraduate studies attendance at lectures was voluntary and it was up to me to decide if, and when, I should consult my tutor. While a PhD student and postgraduate there was no concept of mandated and recorded meetings with my supervisors and the only reports I was expected to prepare were first drafts of eventual publications. When starting as a lecturer at Southampton University, I had about five minutes with the Head of Department, was shown an office and left to get on with it. I had no formal meetings with my “line manager” (indeed this concept did not exist) and I was prepared for undergraduate teaching with a single three hour session. Today undergraduate attendance at lectures is recorded as are compulsory meetings with tutors; sanctions are applied for non-compliance. PhD students have multiple supervisors/mentors and are required to record compulsory meetings with them. A number of intermediate reports must be produced and assessed along the road to graduation with a doctoral degree. Staff have a PDR once a year and are required to complete forms detailing the work they perform and how they occupy every hour at, and away from, work. Although I personally prefer the old system, this article is not aimed at discussing which is better. Rather, it is to enquire how the University implements policy changes, often introduced at the cost of great disruption, to ensure they are based on best current practice. Further, how are the outcomes of these changes determined and any benefits measured?

Conquest quote

A few years ago all undergraduate teachers were informed that they would be required to use the “buddy system”. Here, two academics are paired and required to attend, and write a report, on one of their buddie’s lectures. Although not onerous, I enquired about evidence that such a scheme was beneficial. After much badgering I was eventually sent a link to two publications. The first, admittedly in a peer reviewed journal, consisted of about ten subjects beingcartoon asked if they found the scheme helpful. This paper could be used as an example of how not to do science and I can only assume that the author, a young medical doctor, felt that any publication, no matter how poor, would benefit his future career. The second was not even peer reviewed, rather a trenchant statement of a scheme supporter bereft of any evidence. The purpose of the buddying is assuredly to improve undergraduate teaching and, as we survey our students almost to destruction, I enquired if an improvement in quality had been observed. I received no reply and concluded that this scheme was started on the whim of the dean involved, based on little evidence and with no mechanism in place to observe its consequences. This example is trivial but similar considerations apply to the much more consequential issues addressed in the first paragraph. I have yet to be presented with evidence that constant monitoring and assessing of students and staff is based on rigorous studies that clearly demonstrate positive effects. We survey our undergraduates continually and for postgraduates and postdoctoral workers have data on their accomplishments (do PhDs graduate on time, how many publications result from Bernard phototheir work, what are their future job successes). But this data is never correlated with policy changes to measure their efficacy. Similarly for staff, following the introduction of PDR, has teaching improved, has grant funding increased, have more and better publications resulted? Overall is the University a better place in which to work, perhaps monitored by absenteeism rates, which correlate well with staff happiness. As academics we must insist that anybody introducing new policies should present the evidence underpinning the change. A system for monitoring outcomes, which places minimal burden on students and staff, should be demonstrably in place. While benefits at the individual level may be small they should surely be apparent over the entire University body. Finally anybody introducing procedures based on little evidence or not leading to favourable outcomes should rapidly be removed from any position of authority.

 

 

The ICaMB PhD student symposium: what does it mean to the supervisors?

A strong and vibrant PhD programme is essential for any successful academic department. PhD students bring energy and enthusiasm to their projects (well that’s the idea anyway) that frequently reminds many jaded professors contemplating the hell that is ResearchFish why they went into this business in the first place. Typically a PhD student progresses from hesitant first steps in the laboratory to becoming a confident scientist with ownership of their project. Although in the moments before a PhD viva some of that confidence has been known to slip away. The ICaMB Postgraduate Research Symposium is an important showcase that allows our final year PhD students to demonstrate not just the exciting science they have been doing but also just how far they have come over the last 3/4 years. But there is also a serious side to this for ICaMB. In the last REF (where we <cough> did quite well), our PhD students made a major contribution to our returned papers. Brian Morgan has crunched the numbers and discovered that PhD students were first authors on 30% of our 3*/4* submissions (see Figure), including papers in Cell (x2), Nature, Science, Molecular Cell, Nature Chemical Biology (x2) and PNAS (x3). Moreover, in our UO5 return, 3 out of 4 of our Impact cases were underpinned by PhD student research.

Graph

This year, the first day of the symposium was on March 14th with a second to be held on April 29th. We’ve covered the ICaMB PhD symposium before but this year we thought we’d do something different and ask some of the PhD supervisors what this meant to them. All of us are proud of the PhD students that come through our labs, even if, occasionally, there are some grey hair inducing moments on the way. Seeing a final year student confidently discuss their project and answer questions is an important moment for a PhD supervisor. Below we have a varied group of supervisors, from a definitely not jaded professor discussing their final PhD students, to a newer PI discussing their first.

Harry Gilbert: Ana Luis and Jon Briggs

The two final year students from my laboratory who are contributing to the 2016 Postgraduate Research Symposium are Ana Luis and Jon Briggs. These are my last PhD students and it is great to finish with such excellent scientists. Neither student is on the traditional BBSRC/MRC DTP. Jon is supported by the Faculty to work on my Wellcome Trust Senior Investigator Award and Ana is funded mainly from my overheads and more recently by my ERC grant. Jon did a summer placement with Waldemar and his undergrad project in my lab. I was very impressed with Jon and was delighted he was willing to do a PhD with me. I said to Jon his project could be funded by BBSRC, requiring that he did a PIP (Professional Internships for PhD Students) or the Faculty in which case the three month break was not required. Jon said “I want to do science during my PhD and not be distracted by other activities”. Ana wanted to do a PhD with a glycan lab and came highly recommended by one of my previous PhD students, Carlos Fontes from the University of Lisbon, Portugal. So Ana is doing a three year PhD with no MRes, PIPs etc. Some of us, of a certain age, may remember these type of PhDs.

Harry, Jon and AnaThe two students have worked on glycan degradation by the human gut microbial community, or microbiota. Jon is focussed on the biochemistry of selected enzyme systems and the extent to which there is cross feeding of oligosaccharide products generated during the degradative process. Ana, like Jon, has used molecular genetics and biochemistry to explore the enzymology of these glycan degrading processes, while also using X-ray crystallography to study the structure and function of key enzymes.

Both students are remarkable in that they work on their own project within a largish collaboration. This is fine but on a regular basis, well almost weekly, they are given “the opportunity” by their supervisor to alter the objectives of their project almost on a weekly basis. They adapt to these unusual demands brilliantly. We all have tremendous respect for both students; they work extremely hard, are technically excellent, flexible and, most importantly, think carefully about their science, designing and carrying out a series of decisive experiments to resolve critical components of the glycan degrading process. Maybe the best testimony I can provide is that it is not possible to distinguish Ana and Jon from the postdocs in the lab, they are an inspiration to all of us.

 

Paula Salgado: Adam Crawshaw

Paula and Adam

Being your supervisor’s first PhD student can be a mixed bag. You will get a lot of their attention, so help will always be available. But at the same time, as they find their way as independent researchers, any issues will be closer to your own progress than for many of your colleagues. As I saw Adam present his work at the ICaMB Postgraduate Research Symposium, I was reminded of my own journey as a “first student”, several years ago. As I shared my supervisor’s progress, so has Adam shared mine. It has been fantastic seeing him develop, visibly learn and acquire so many skills. Even when his project didn’t go according to plan and experiments were proving hard, he didn’t lose the drive, the enthusiasm. It was with pride that I saw him give a confident talk, answer questions and be humble enough to challenge his own work. He has learned many techniques, from crystallography to circular dichronism, from molecular biology to NMR – he took it all in willingly and enthusiastically. His contribution to understanding several aspects of Clostridium difficile pathogenicity will be in the scientific papers produced, as well as in the future of my “Structural Microbiology” lab. It was great to hear him present all the work he did over the last 3.5 years to our colleagues. Well done!

 

Dianne Ford: Joy Hardyman

 Joy Hardyman’s presentation at the ICaMB Postgraduate Student Research Symposium was on the topic of zinc, which we have studied in our lab for many years. Joy’s PhD research is funded by an MRC studentship, which not only gave Joy the opportunity for research training but also really allowed us to add value to data we collected as part of a BBSRC grant, and generated an additional publication (Hardyman JEJ et al (2016) Metallomics (in press)).

Dianne and Joy

Global zincThe lab’s focus is the basic cell biology of zinc, which is essential to understanding zinc nutrition. Zinc nutrition is a global health challenge, with an estimated 17.3% of the global population at risk of inadequate zinc intake. Also older people, including here in the UK, are particularly at risk of sub-optimal zinc intake or low plasma zinc concentrations.

Zinc rich foodsAt the end of our BBSRC grant we had some intriguing microarray data that we had set aside because we struggled initially to make sense of it. We had depleted cells of a transcription factor known to have a role in zinc homeostasis (MTF1) then challenged them with zinc, with the aim of identifying the gene targets of this transcription factor. However, rather than see gene responses to zinc being attenuated we saw ‘sensitisation’ of the transcriptome response to zinc. We now know that this is because the usual response of the intracellular protein metallothionein, which effectively ‘mops up’ intracellular zinc, was attenuated because this response is under the control of MTF1.

We all need zincInterestingly, we now think this model, where MTF1 is depleted, may allow us to study what happens to zinc homeostasis in cells as they age, because cells from older individuals have higher levels of metallothionein. Thus, cells with MTF1 depleted may represent a ‘younger’ phenotype. We will now explore the suitability of this as a model of zinc balance in the ageing cell with a view to using it in further research to gain a better understanding of zinc dys-homeostasis in older age.

 

Kevin Waldron: Anna Barwinska-Sendra

Anna’s project began as something of a ‘sideline’ of research in my lab, something that I’d originally initiated when I first started my own independent research back in 2010 but then put on the back burner due to limited resources when my ‘lab group’ consisted solely of me. I re-initiated the project when Anna approached me for a short period of work experience in my lab in 2012. It is a tribute to Anna’s drive and enthusiasm that, within just a few days of her being in my lab, I was keen to keep her on in some form, and I was delighted when she later accepted my offer of a PhD studentship to continue this project in my lab. It’s one of the best decisions I’ve made in my short time as a PI.

Kevin's lab

I set Anna the task of determining the metal specificity of the two superoxide dismutase (SOD) enzymes that are encoded within the genome of Staphylococcus aureus. SODs are essential for the bacterial defence against the reactive oxygen species (ROS) superoxide anion, and both of these enzymes were predicted to be manganese-dependent. However it was emerging that, during infection, pathogens such as S. aureus experience host-imposed manganese starvation, a process termed nutritional immunity, which raised the possibility that one or both of these enzymes might be able to use an alternative cofactor for catalysis, most likely iron. Anna has confirmed that one of these enzymes is cambialistic in vitro, which means it is catalytically active with either metal cofactor, something that’s exquisitely rare amongst metalloenzymes. We hypothesise that this cambialistic property of this SOD is a mechanism by which S. aureus is able to circumvent nutritional immunity and resist the onslaught of oxidative attack during manganese starvation.

Anna has been an exceptionally productive student during her time in my lab, and I’ll be sorry to lose her when she completes her studies later this year. She has a bright future in research. Her project also highlights the importance of PhD student projects to a ‘basic research’ lab like mine, as they enable more exploratory, high-risk, high-reward projects such as this, and allow us to take our research in whole new directions that would not be possible within the constraints of traditionally-funded, Research Council grant-based projects.

 

Jeremy Lakey: Alysia Davies

Alysia poster prize

Alysia’s studentship is rather unusual as it is funded by the BBSRC, Bioprocessing Research Industry Club (BRIC) and has a partner company, Pall, who make a huge range of products used in the production and purification of biomolecules. BRIC is a very proactive organisation that meets twice a year for students and post docs to present their work. It also arranges training and skills schools to enhance the employability of the graduates especially those wishing to enter the fast growing bioprocessing industry. This industry is responsible for delivering the next generation of treatments based upon large protein and DNA molecules rather than small molecules such as penicillin. The magic bullets in all this are immunotherapies based upon large proteins called monoclonal antibodies. These are used in the treatment of many conditions such as cancer (Avastin) or rheumatoid arthritis & Crohn’s Disease (Humira). One difference with such large molecules is that they can provoke an immune response which prevents further treatment. Such responses are more common if the proteins stick to each other; a process known as aggregation. Alysia’s project is to develop rapid tests for aggregation so that problem batches can be detected early in the factory and removed. We hope these tests will make the medicines both safer and cheaper.

 

David Lydall: Joana Rodrigues and Marta Markiewicz

Joana Rodrigues, from Portugal, and Marta Markiewicz, from Poland, will complete their EU (Marie Curie) International Training Network funded PhDs very soon.   On this basis I will vote to stay in Europe.

Lydall lab

As a supervisor I have been delighted to have Joana and Marta in my lab.  It is really rewarding to have bright, enthusiastic, international members of the lab.  Very often the most rewarding aspect of my job is observing PhD students gain confidence, experience and strength during their comparatively short time in the lab.  I think this has certainly been the case for Joana and Marta and they both gave excellent talks at the symposium.

As is usual, at least in my lab, the projects Marta and Joana have pursued have drifted substantially from where they started.  It is one of the most fun aspects of supervising PhD students that there are few, if any, “milestones” to be met during a PhD.  Despite this chaos, philosophy usually occurs, doctorates are earned and knowledge improves.

Joana and Marta have each worked in budding yeast on proteins that are conserved in human cells and that affect cancer.  Joana has made substantial inroads to our understanding of how the PAF1 complex interacts with and affects telomere function.  Marta has shown how Dna2 protein, known to be important for DNA replication, may play its most important functions at telomeres.  We are just in the process of submitting papers from both Marta and Joana.  They have also each agreed to stay in the lab for a further year to capitalize on all their hard work.

Joana and Marta were recruited to the Codeage International Training Network, which is centred in Cologne (http://itn-codeage.uni-koeln.de).  For all three of us this was our first involvement in such a network.   It has been a lot of fun and we have networked our way from Cologne, to Crete and Milan.  We are looking forward to the final meeting in Crete in September.

Jeremy Brown: Shiney George and Man Balola

I have 3 PhD students in the final year of their studies. 2 of them, Shiney George and Man Balola gave excellent presentations on their work on translational control of viral gene expression in the Symposium earlier this week. My lab has been dependent on PhD students for the last few years, and I can only thank them for the positive contribution that they have all made to the lab’s research output: without them there would have been little, if any, progress. Nearly all the lab publications in the last few years have had PhD students as first authors, and the current group have generated excellent data for the next papers that we will publish.

Jeremy's lab

My students over the past few years have had very different sources of support, from self-funded through sponsored to Research Council support. This has led me to reflect on the disparities between funding arrangements, and also how this and the structure of PhDs has changed over the years. I was very lucky when I did my PhD – I was the recipient of a Welcome Trust Prize Studentship. These were quite a novelty at that time, a relatively new scheme, with more generous stipend than other studentships, but the same length – 3 years – as most other studentships. At that time pretty much all PhDs were: go to the lab; do the work; learn the trade; write the thesis.

In the years since my time as a PhD student there has certainly been a shift in how PhDs are organised with alterations to funding for students, various add-ons in terms of knowledge and skill training being tried and in some cases discarded, and a move towards longer, 4 year, training. Some of this could be argued to have diluted the important ‘learn the trade’ part of a PhD, though there are clear pros to enhanced training too. Perhaps more worrying though, there is considerable disparity in the provision for students funded from different sources. One obvious issue is the budget for laboratory costs, which is woefully inadequate for many studentships, but much more adequately costed from others. This has to impact at some level the ambition and scope of PhD projects. Another issue is that while the formal length of PhD (i.e. the time from starting to when the book has to be submitted) is pretty much standard at 4 years, there are differences in the length of funding of PhDs. As we know, as staff in ICaMB we can apply for 4 year BBSRC studentships, 3½ year MRC, and faculty studentships (including this year the Research Excellence Academy) that provide 3 years.

There are few level playing fields in life, but as a PhD is an academic qualification one might naively expect that the duration, resources and other support should, where possible, be similar, at least within a country. Why are there such disparities, how confusing must this be for anyone hoping to employ someone with a PhD? Bioscience needs bodies and PhD students are the backbone and key work-force of a good number of laboratories (mine included). There is then strong competition between academics for studentships each year – evidenced particularly by the very large number (>150) of applications for faculty studentships this year – and disappointment for those who are unsuccessful. Conversely there are many aspiring to a career in bioscience for whom a PhD is a key step. So, there are strong reasons to spread the available resource as broadly as possible, and it is easy to rationalise the way in which resources are being used. I would make the comment (my personal view) that at a time when significant efforts being made to even out opportunities at a number of career stages, we should when possible make sure that we do not undermine this at the early stages, by having some PhD students advantaged over others. And this is before the vagaries of supervision, luck and other factors kick in.

Climbing the Tree of Life

MartinIn this week’s blog, Professor Martin Embley reflects on the  the journey that led to him, his collaborators and his laboratory to fundamentally change our views on evolution and the Tree of Life.

The Early Years

My early career was a bit of a random walk while I tried to figure out what I really wanted to do. After my PhD in Newcastle on bacterial diseases of trout and salmon, I got a job teaching industrial microbiology at North East London Polytechnic in 1984. It was an odd but interesting place, a number of staff appeared to have strong religious beliefs of various sorts and wanted to talk about them, and one colleague thought he could change traffic lights from red to green so he never had to slow down. I was keen to keep doing some research and I was interested in evolution, but like a lot of newly independent researchers I struggled to get any funding. My big break came when I got a “cultural exchange” grant from Newham Council to go to Poland to learn some molecular biology and I met Professor Erko Stackebrandt who was passing through. Erko had worked with Carl Woese in pioneering the use of ribosomal RNA sequences to investigate evolutionary relationships among prokaryotes. I persuaded him to let me visit his lab in Germany to learn the new techniques and in 1991 these skills got me a job at the Natural History Museum in London.

The Museum wanted to set up a lab using molecular sequences to investigate evolutionary relationships. The film Jurassic park was just about to appear and there was tremendous excitement about the potential of ancient DNA. The Museum gave me free rein regarding my own research as long as it had evolution at its core. So I decidedTree of life to work on the early evolution of eukaryotic cells. At the time two ideas were central to views of early eukaryotic evolution. One was that the “three domains tree of life” was an accurate description of the relationships between eukaryotes and prokaryotes (you can see the tree here). The other was that some eukaryotes, including obligate intracellular microsporidian pathogens, had never had mitochondria because they split from other eukaryotes before the mitochondrial endosymbiosis. I’ve been trying to test these two ideas for the past 25 years and while it’s often been difficult and frustrating, it has also been a lot of fun.

A Team Effort

Like most PI’s I’ve relied on attracting talented young scientists to do the work that we have published. Robert Hirt walked into my lab off the street and asked me if he could do a project involving eukaryotic evolution and ecology. He already had a first author paper in Cell and now he wanted to do something different. We didn’t do much ecologMitochondriay together but Robert and I co-supervised PhD student Bryony Williams who showed that microsporidians actually contained a tiny, hitherto overlooked mitochondrion, now often called a mitosome.

Unlike our own mitochondria, the microsporidian mitosome doesn’t make ATP, because it has lost all of the pathways used by classical mitochondria to make energy. Alina Goldberg in our lab – now at Newcastle – and Sabine Molik in the lab of Roland Lill in Germany spent Mitochondria 2the next seven years showing that the mitosome functions in the biosynthesis of essential cytosolic and nuclear Iron/Sulphur (Fe/S) proteins. The discovery of a tiny mitochondrion in microsporidia (Figures 1 and 2) was an important piece of evidence that led to current ideas that the mitochondrial endosymbiosis occurred at the origin of eukaryotes. Thus, it is now thought that all eukaryotes contain an organelle related to mitochondria, and its most conserved function is in Fe/S protein biogenesis, not ATP production.

Figure 1Figure 2Competing Hypotheses

In the three domains tree of life, eukaryotes are a separate domain that is most closely related to the domain Archaea and the host for the mitochondrial endosymbiont is already a eukaryote. Although this hypothesis appears in most textbooks, there have actually been a number of alternative hypotheses published over the years (Figure 3 shows one of them), but these have largely been ignored. Cymon Cox spent three years analysing molecular sequence data to identify which of the competing published hypotheses was best supported and reached the surprising conclusion that it was not the three domains tree but an alternative hypothesis called the eocyte tree (you can read a discussion about the differences between the two trees including a picture of the eocyte tree here). In the eocyte tree, eukaryotes originate from within the Archaea, suggesting that eukaryotes are not a primary domain of life like Archaea and Bacteria, but are instead a product of genetic and cellular contributions from both prokaryote domains. Very excited by these results, we sent Cymon’s paper to Nature where it was reviewed and quickly rejected. We appealed, it was revised, it was reviewed again, and it was rejected again, all in all pretty dispiriting, but a common experience for most scientists. However, after hearing me talk about Cymon’s work at a meeting, we were invited to submit Cymon’s paper to PNAS where it was finally published in 2008.

Figure 3A Mixed Response

Although Cymon’s paper has been highly cited it is true to say that the initial response from the community was very mixed. We received emails suggesting that we had manipulated our results to get the answer we wanted and one of the reviewers told us that it was impossible to infer such ancient events using molecular sequences. In responding we agreed that it was difficult to be confident about anything that happened billions of years ago based upon small amounts of data and even the best methods of analysis, but that people in the field seemed happy to use the same data and worse methods to support the three domains tree. Cymon eventually moved on, scarred but not defeated, and Tom Williams took over the project when he came to Newcastle on a Marie Curie Fellowship in late 2010. Over the next few years, more data was published as new Archaea were discovered and new methods of analysis were developed, and every analysis that Tom, or others, did on these data produced a version of the eocyte tree, so that it is now the best supported hypothesis – at least in our opinion.

More evidence emerges

Hypotheses are only useful when they make predictions that can be tested by further research, and evolutionary hypotheses are no different. The eocyte tree predicts that new species that share more features in common with eukaryotes will be discovered among the Archaea, and this prediction now appears to have been spectacularly fulfilled by recent discoveries from Thijs Ettema’s lab in Sweden. The new paper describes the discovery, so far only from metagenome data, of an archaeal lineage called Lokiarchaeota that contains many genes for proteins that were previously thought to be eukaryotic specific, including homologues of proteins used in the eukaryotic cytoskeleton, in membrane remodeling and in phagocytosis.  This is incredibly exciting and the challenge is now to isolate Lokiarchaeota and other new lineages into culture so that their biology and physiology can be studied in the laboratory.

An Interesting Journey

Scientific work is often written up as if it were a linear progression towards improved understanding, a type of “Whig history” which does not accurately reflect how science is really done. In reality, science is a collaborative endeavour with lots of dead ends, confusion and false trails, and we could easily be walking down some of those still. Nevertheless, the currently prevailing paradigm for eukaryotic evolution is now very different to the popular views held in the 1990s when I started my research career. All eukaryotes are now thought to contain a mitochondrial homologue that generally functions in Fe/S protein biogenesis, and the host for the mitochondrial endosymbiont is thought to have originated from within the Archaea. Eukaryotes are thus viewed as the product of an interaction between (at least) those two prokaryotic partners and are not a primary domain of life but one derived from prokaryotic antecedents. The complex features that we take to define eukaryotic cells including our own, such as the nucleus, large genomes and diversity of RNAs, are thus secondary features that have evolved since those primordial interactions. I’m not sure what my religious former colleagues would have made of the work I’ve done since leaving NELP, but it’s been an enjoyable and interesting journey for me.

Links

The Tree of Life: http://www.pnas.org/content/87/12/4576.full.pdf

Bryony Williams’ paper: http://www.nature.com/nature/journal/v418/n6900/full/nature00949.html

Alina Goldberg and Saline Molik paper: http://www.nature.com/nature/journal/v452/n7187/full/nature06606.html

Mitochondria and Fe/S proteins: http://www.nature.com/nature/journal/v440/n7084/abs/nature04546.html

The eocyte tree: http://phenomena.nationalgeographic.com/2012/12/20/redrawing-the-tree-of-life/

Cymon Cox paper: http://www.pnas.org/content/105/51/20356.full

Tom WIlliams paper: http://www.nature.com/nature/journal/v504/n7479/full/nature12779.html

Thijs Ettema lab paper: http://www.nature.com/nature/journal/v521/n7551/abs/nature14447.html

Athena SWAN – deconstructed

In the second of today’s dual posts, we hear from Nancy Rios, Athena SWAN project officer for Newcastle University’s Faculty of Medical Sciences. Nancy explains why Athena SWAN is necessary, and how ICaMB aims to change its gender imbalance.

Athena SWAN – so what’s it all about? According to the tin, Athena SWAN is a charter set Bronze awardup by women’s networks to tackle the under-representation of women in STEMM. The model is simple – we analyse our local situation, evaluate our working practices and then develop strategies and actions to make the workplace fairer for everyone. Universities and their departments can apply for either a Bronze, Silver or Gold award (renewable every three years). ICaMB has recently been awarded a Bronze award. So far, so good.

Why Athena SWAN? Let’s start with the evidence.

In FMS, around 60% of undergraduate students are women.

Figure 1

 

In ICAMB, approximately 50% of PhD students, 40% of Postdocs, 50% of Fellows and 15% of permanent academic staff, including only 10% of Professors, are women.

Figure 2

Figure 3

These numbers aren’t unusual. In fact the alarming drop out rate and low proportion of women in senior, strategic positions is typical in STEMM departments in universities all over the country. So there’s the statistical evidence – women scientists aren’t progressing in academia at the same rate as men.

Lab picturesSo why does all this matter? Why make gender equality something that should be addressed in our workplace? Being concerned about the loss of women scientists isn’t about being politically correct and nor is it about feminism. Athena SWAN is about developing a competitive and effective workplace and making the most of all of our talent for the benefit of the University and for science. It’s about becoming a modern and dynamic employer that understands that women and men both become parents or carers and both make great scientists. Quality needs diversity. Recent research shows that teams and boards that include women make better decisions and perform better in business. That’s why diversity is a priority for our university.

OK, but why are so many women leaving? Maybe women just don’t want to stay in science. You can’t chain anyone to a bench and why would you want to? Actually, when you look at the evidence, the reasons that women leave are varied and complex. They lie in a combination of structural, cultural and systemic factors, both conscious and unconscious bias. Biology is a factor too, of course. Even though parental responsibilities can be shared, adding to the family just does have more immediate impact on the mother.

Bias may be a dirty word, but if we pretend it isn’t happening, we can’t do anything about it. In a very recent and rather hair-raising example of blatant bias a peer-reviewer suggested two female biologists get a man to co-author their paper to improve it.  Another more local example came from a researcher who was asked at a job interview (at a different university) whether or not she was planning children. She said she wasn’t, and the panel asked her how she knew. There is also the less obvious unconscious bias that we all inevitably have. Unconscious bias means that our behaviours and the decisions that we make are influenced without our knowing it by preconceptions that we’ve been developing since birth. Our brains develop short cuts that cause us to make assumptions and ignore objective facts. These shortcuts are natural and necessary for survival, but they are not so good for business. Evidence would suggest that unconscious bias can have an impact at work at any level you care to think about.

For example Moss-Racusin et al, 2012, found that professors (of both genders) when evaluating applications from students for a post of lab manager rated the ‘male’ applicant more competent and hirable, and offered a higher starting salary, than that of an otherwise identical ‘female’ applicant.

A 2014 study showed that when students were asked to rate teaching instructors of online courses they rated the male identity significantly higher than the female identity regardless of the actual gender.

And this bias can make a difference to which students are encouraged or ignored, who is asked to present group data at conferences or who is asked to make the tea. Biases can also make a difference to how much we feel we can achieve for ourselves.

There are also structural factors that can impact women more than men – out of date procedures and systems that make it hard to balance working with family life. For example, it tends to be more difficult for women to engage in networking opportunities, meetings and seminars after hours. Short term contracts, working abroad, travel, a ‘long hours’ culture and few opportunities to work part time are difficult for both men and women who have children or other dependants to look after.

It’s great to hear that researchers like Suzanne do not feel that they have personally experienced any discrimination. Unfortunately less positive accounts of women’s experiences at work are frequently heard. For example the PhD student who loved her field but wasn’t planning on staying beyond until her late twenties because she wanted to have a family and saw this as incompatible; an academic who got ill to the point where she was on medication trying to manage the transition back to work after maternity leave – she ‘didn’t dare’ ask for help; a professor in her 50s who pondered over whether the sacrifice she’d made twenty years earlier – she decided not to have children, in order to pursue her career – was really the right decision. There are accounts of bullying (gender related), discrimination (gender related) and resignation (in all senses of the word).

So what can Athena SWAN do?

SoapboxIn ICAMB, we’re using the Athena SWAN process to try and redress the balance and work towards a fairer workplace for all. For example, we looked at the first big attrition point for us – the transition from Postdoc to Lecturer. We found out that mentors were generally only available to Postdocs with fellowships, so we set up mentoring schemes to enable all Postdocs in FMS to access a mentor. We found that both women and men were unaware of what support they were entitled to around maternity and paternity leave and flexible working, so we’ve made an effort to highlight and publicise policies. We’ve committed to ensuring that all staff involved in recruitment panels attend training in unconscious bias. We provide additional time and money to support staff to attend training courses. We’ve started holding seminars at different times and we organise ‘equality in academia’ events. We are also engaging with national projects such as Soapbox Science.

Equality day

We are working with colleagues across FMS and the University on Athena SWAN. We are lobbying the University to provide a nursery with affordable creche provision for all staff. We’ve heard that many women have found it very difficult when returning from maternity leave to get their research back up to speed – so we’re in the process of setting up a programme that will offer research active staff (men and women) additional support at that time to make a successful transition back to a research career.

These are just a few of the small changes that we’ve started to make under Athena SWAN to make the workplace fairer for everyone, but it’s just the start of a journey. There are a plethora of other issues that are emerging that people are asking us to think about. What’s going on with our recruitment procedures that means we sometimes have so few women applying? How can people gain experience on committees? Can we simplify and update our policy around bringing children into the workplace in a fair but sensible way?

You may have noticed that the vast majority of actions benefit men as well as women, and ICAMBthere are changes that have a positive impact on everyone. That is why it is so important to get as many people as possible involved. We would love to have more volunteers on our Athena SWAN team to help out with input, ideas and challenges and help us achieve a Silver Award in the near future! Culture change is difficult and it’s inevitable that we won’t always get things right first time, so the more feedback we get, the better.

It’s concerning that Athena SWAN is so often misunderstood. There are ‘urban myths’ that it is about positive discrimination and giving women a ‘leg up’ the career ladder. If you think about it, this view is insulting to everyone. Let’s use the analogy of a footbal game – this isn’t about giving any player an advantage over another, its simply about levelling the pitch. We welcome an open discussion of the issues, of all the things that have been achieved so far and how they can be taken further.

Athena Swan team

Links

https://heidi.hesa.ac.uk/

http://news.sciencemag.org/scientific-community/2015/04/sexist-peer-review-elicits-furious-twitter-response

Moss-Racusin et al, 2012: http://www.pnas.org/content/109/41/16474

Online course rating: http://link.springer.com/article/10.1007%2Fs10755-014-9313-4

Soapbox Science: http://soapboxscience.org/

When a Teardrop Can Kill: The Deadly Ebola Virus

AnjamMarch 22nd marked a grim first anniversary: what we now know is the deadliest Ebola outbreak to date was officially announced by the WHO in Guinea. Since then, news reports have featured the dramatic and worrying outbreak of Ebola virus infections in West Africa. In our blog post this week, ICaMB’s Dr Anjam Khan reviews this deadly but scientifically fascinating killer and reflects on his recent experiences discussing the virus in the media.

By Dr Anjam Khan

Prophecies of Science Fiction

Andromeda StrainAs a school kid I was fascinated by science fiction and the visionary predictions made about future technology by the fathers of this genre, Jules Verne and H. G. Wells. Science fiction writers have also forewarned of global catastrophes ranging from those caused by climate change, to the annihilation of the human race by a virus concocted in the lab of a mad scientist! A book called “The Andromeda Strain”, by the best-selling author Michael Crichton, captivated me. The story was set in Arizona. It followed a team of scientists in a secret high containment lab trying to control the apocalyptic spread of a deadly extra-terrestrial microbe. The infection rapidly caused lethal blood clotting in its victims, or “disseminated intravascular coagulation” to us nerds! The crystalline alien microbe “mutated” at an extraordinarily high frequency, almost instantaneously acquiring new biochemical skills such as the ability to digest through plastics and rubber seals. These are attributes synthetic biologists dream of constructing today in “environmentally friendly” bugs to degrade plastics!

The Devastating Realities of Ebola The deadly Ebola virus outbreak is not from the realms of science fiction but written by nature. This outbreak has shocked the world not only because of the high mortality rates, but due to the horrific disease it causes. The virus has quickly spread and brought the three West African countries, Guinea, Sierra Leone, and Liberia, to the their knees, and to the brink of economic collapse.

West Africa

Map of West Africa with Guinea, Sierra Leone, and Liberia highlighted. Image from copyright free – morguefile.com

Reports of the first cases of Ebola in Europe and the US brought panic and fear to those who previously thought this deadly plague was confined only to West Africa. Undeniably, governments and healthcare organizations were all taken by surprise, and were ill prepared to rapidly deal with the disease or indeed its global threat. Why had Ebola taken the world by surprise? The warning signs have been there for almost four decades! The first case of the disease was described in 1976 in Zaire (now the Democratic Republic of Congo), near the Ebola River from where the virus gets its name. With the present outbreak there have been over 23,000 reported cases with approximately 10,000 deaths. The human toll in fatalities has been almost 10 fold greater in the current outbreak than all the previous outbreaks put together!

Genetic serial killer 2

Politics of Disease Control and Media Engagement The world hesitated in responding to the emerging Ebola crisis, naively hoping the disease would burn itself out. This did not happen and the number of newly infected individuals increased week on week. Some politicians and members of the media fuelled the fears of the masses. Our government hurriedly announced it was establishing four NHS hospitals, including the Newcastle Royal Victoria Infirmary, as Ebola centres with highly trained staff and fully equipped facilities to deal with Ebola cases.  Furthermore, compulsory thermal scanning of travelers arriving in airports from selected destinations was introduced, in a bid to spot anyone with a fever and potentially infected with Ebola. There are, however, many other infections and health conditions which can also induce severe fever.

Screening

Thermal cameras to detect passengers with high fevers were recommended in airports for screening for potential Ebola infected individuals. Photo Credit: cdc.gov

Hence, in reality this screening approach was only of limited value in identifying Ebola infected travellers, and perhaps served more as a placebo to allay the fears of the public. For example, Thomas Eric Duncan was thermally screened upon arrival in Texas, and he later developed full-blown Ebola and sadly died of the disease in Dallas. Two nurses treating him also became infected.

The national and local news media wanted to find out more about Ebola and the control measures being put in place. With a background in infectious diseases, I was asked to provide insight into the virus and the disease it causes. Normally I would run a mile from being in the public eye. But given some gentle encouragement, decided on this occasion to raise my head above the comfort zone of the academic parapet, and try to provide sensible and factually correct advice on the virus and the disease. Following my first interview with a local newspaper the requests for interviews increased, and within a few weeks I had given three television, four newspaper articles (Northern Eco, Chronicle, The Week), and a radio interview! This included one live TV interview for BBC News 24 via a satellite link, which was petrifying! It was challenging not only because it was being transmitted live, but due to the technical arrangement – but that’s a blog for another day! Speaking to the media was a brand new experience for me. It was certainly a steep learning curve and I realised the importance of “sound-bites”: you can be interviewed for 20 minutes but the editor may only select two 15 to 20 second excerpts for airing. Furthermore you quickly realise you have no editorial control of the content or indeed the context of your quotes!

Pirates of the Immune System

Fruitbat

A typical fruit bat: Photocredit: Wikipedia.org

The first Ebola outbreak in 1976 was identified in Central Africa, and it has now spread to Western Africa. This distance at first glance may not sound very far, but to put this into perspective, it is comparable to the distance between Newcastle (UK) and Quebec (Canada) or between Newcastle and Cairo (Egypt)! A key factor contributing to this spread could be the fruit bats, which harbor the virus, flying and migrating to new habitats. For reasons unknown as yet, some fortunate individuals can recover supported by simple hydration therapy. These survivors provide a hugely invaluable resource of biological information, and will undoubtedly provide important insights into understanding the Ebola text and pictureimmunological correlates of protection or the genetic basis of resistance to Ebola. But sadly for the vast majority of infected individuals, the disease is devastating. The cunning virus “pirates” the immune system and incapacitates the anti-viral machinery of the immune cells by blocking the “interferon alarm” from sounding in target cells. The virus then triggers a “cytokine storm” triggering the release of potent inflammatory molecules into the circulatory system that wreak havoc throughout the body, and causing organs such as the liver and kidneys to fail. Blisters of blood erupt below the skin. During these final stages of haemorrhagic fever clotting factors can become depleted (compare to the Andromeda Strain!), and blood vessels start to leak profusely, heavily tainting vomit and diarrhoea with blood. Shockingly, infected individuals literally bleed to death through every bodily orifice from their eyes to their ears! . It is during this final phase the virus is most infective due to the very high concentration of virus particles in the blood and body fluids. Undiagnosed patients can inadvertently spread the killer disease to family and healthcare workers. There is nothing more heart breaking than watching a distraught infected mother not being able to hug and console a crying child for fear of spreading the disease. This is an unforgiving virus and literally a teardrop can kill!

The Achilles’ Heel of a Giant

As we learn more of the biology of the Ebola virus, scientists are uncovering ways to prevent or tame infections. The fatal power of this giant-sized virus is largely attributed to a single protein, known as the “spike-protein” and is the virus’s “magic wand”. Located on its surface, this protein is crucial for infecting cells, as well as manipulating the immune system. The shrewd virus cloaks and masks key domains of this protein using sugars, allowing it to evade the patrolling cells at the frontline of our immune systems. This spike-protein could also prove to be the virus’s Achilles’ heel, and insights into its structure will enable scientists to design new vaccines and drugs to target and inactivate vulnerable uncloaked regions in this essential protein.

Vaccines and drugsThere are now prototype vaccines under development and undergoing fast-tracked human trials. A therapeutic cocktail of genetically engineered monoclonal antibodies known as ZMapp have been successfully used to neutralize the virus, providing passive immunity and protection against disease. The Ebola outbreak has also motivated me to return to my background in vaccine discovery and help contribute towards the development of vaccine against Ebola. To this end I have established a collaboration with my good friend Pietro Mastroeni (Cambridge) and Gary Kobinger (Canada). Gary is a pioneer in the field of viral haemorrhagic viruses, and senior author of the recent article in Nature describing the reversion and protective effects of the ZMapp antibody cocktail against Ebola. Our strategy will be to use synthetic biology to engineer an oral delivery platform for the vaccine, obviating the need for needles and syringes, or the requirement for refrigeration.

Global Health Security

Global Health security

Global health security www.cdcfoundation.org

Ebola has been considered a rare disease and consequently very little money has been invested in research or the development of therapeutics or vaccines to protect against disease. Big pharma have certainly steered clear for commercial reasons. The world governments, pharma, and international healthcare agencies need to co-operate and forge an alliance in readiness to prevent this and future outbreaks of infectious diseases from happening again. The international community has been slow in learning from the re-emergence of polio, cholera, or from the recent outbreaks caused by pathogens jumping from animals to humans. These include bird or swine flu (H7N9; H1N1), and the severe acute respiratory syndrome coronaviruses SARS and MERS. To keep the world safe from threats of infectious diseases, a major input of finance and resources from the national and international communities is required to provide essential support for research in microbiology and immunology, and establishing the necessary medical and management infrastructures essential in dealing with future episodes of Ebola. The present Ebola outbreak fortunately is now being brought under control. However in recent days there has been a British healthcare worker who has become infected in Sierra Leone, and her close contacts have also been flown back for treatment and monitoring in London and Newcastle. Fortunately, the Ebola outbreak will not become the global pandemic we all feared, and the UN predicts the outbreak will be over by the summer of 2015. However, big questions remain: Where does the virus go to in between these sporadic and unpredictable outbreaks? Does the virus fester away increasing in numbers in populations of fruit bats, waiting for the opportunity to jump across into primates? This is my great fear! The world should treat the present tidal wave of Ebola as a wake-up call. I hope I am wrong, but suspect complacency will prevail as Ebola begins to fade in our memories over the coming months. There is an apt quote from William Arthur Ward “The pessimist complains about the wind; the optimist expects it to change; the realist adjusts the sails”. The international community must become “realists”, and adjust their responses to act now and fulfill all their promises of funding and resources! Otherwise, this could provide a tragic opportunity for a microbiological tsunami to hit the shores of every country!

What did the Black Death ever do for us? The curious route to an Industrial Biotechnology Catalyst Grant

JeremyUK Government Minister Vince Cable recently announced the results of the first round in the BBSRC-supported Industrial Biotechnology Catalyst scheme where  £20 M was distributed across 23 projects. Here, ICaMB’s Jeremy Lakey describes the curious scientific route that led from researching Yersinia pestis, the bacteria responsible for the bubonic plague, to a potential biotechnology breakthrough.

The black death

By Professor Jeremy Lakey

The project that I put together with Neil Perkins (ICaMB), Dave Fulton (Chemistry), Matt German (Dentistry) and Nick Reynolds (Dermatology), called (rather snappily I think) Manufacture of complex protein polymers for industry and medicine, is one of the recently announced Industrial Biotechnology Catalyst awards. It’s a £2.4 million research programme with a BBSRC 80% contribution of  £1.8 million and quite honestly a year ago I’d never imagined having this amazing five years funding to realise this project that has nagged at me for at least the last five years.

 

The early years

Caf1 text v2My interest in the Caf1 protein first arose from a project with the Defence Science and Technology Laboratory (DSTL) on vaccines against possible bioweapons such as anthrax and plague. Other labs had shown Caf1 to be a chaperone usher (CU) family protein, secreted through the outer membrane of the plague bacterium Y. pestis as non-covalently linked polymers. However, most members of this family were visible under the electron microscope (EM) and had a defined structure. We tried in vain to see it under the EM for a couple of years and had given up but, as luck would have it, the world authority on EM observation of proteins using negative stain, Robin Harris, had retired from his job in Germany and moved to Hexham a town in the Tyne Valley near Newcastle. He agreed to have a look with my student at the time, Andrei Soliakov. By adding very low concentrations of protein and using his magic staining recipe, they got amazing images on the first day (see figure). I was on the other end of a country modem at my brother’s farm and so for me the images unfolded slowly down the screen. Robin, Andrei and I (much later in the day), were thus the first folk ever to see one of the key proteins of the Black Death which, between 1346 and 1353, killed up to half of the population of Europe. It was one of those sobering moments in life.

 

Caf1 EM and structure

The Caf1 polymer as seen using an electron microscope (top). The structure (middle) resembles a line of circus elephants (bottom).

We also imaged these amazing molecules on the vaccine adjuvant, they looked like Christmas paper chains hanging off the sides of the adjuvant particles.  No one had seen Caf1 or proteins on adjuvants before, even though most of us have been vaccinated using this material.  I was swept away by the sheer coolness of the data we had and submitted a paper to Nature, then Science, then somewhere else and somewhere else after that but it soon appeared no one was quite as amazed as I was. This remains true to this day with the eventual paper in Vaccine (Ref 1 below) still only having 2 non self- citations; something I still fail to understand.

It’s love actually

However I was seriously smitten by this molecule and hardly cared. This infatuation was made worse one day when, in a seminar, somebody showed the structure of the extracellular matrix protein fibronectin or at least the domains around the integrin binding sites where the well-known RGDS sequence motif is situated. These protein domains looked just like Caf1 because they were both immunoglobulin-like domains.

Different immunoglobulin-like protein topologies (from Pyburn et al, PLoS Pathog. 2011)

Different immunoglobulin-like protein topologies (from Pyburn et al, PLoS Pathog. 2011)

Of course, I should have seen this before as I go on and on and on about protein families in my second year undergraduate lectures. About 70% of cell surface and extracellular matrix proteins are built at least partly from this simple domain structure. Like other superfolds such as the TIM barrel and globin these are protein structures with no sequence homology that are found in large numbers across biology and partly explain why there seems to be a limit to the number of different protein folds (Ref 2). But that is a story for another day.

The immunoglobulin-like fold is found in immunoglobulins (surprise, surprise), MHC, fibronectin, many surface receptors such as EGF receptors etc. etc. It’s also found in the largest protein known, Titin, which stops our muscles over extending when they are stretched. Now it turns up in this Caf1, which is beginning to nag me constantly with the thought that surely I could make things from this amazing polymer. So, off I go to the BBSRC with Mark Birch as co-investigator. With Liz Mitchell we had just shown that we could induce bone formation by growing osteoblasts on surfaces coated with engineered small proteins containing sequences from Bone morphogenic protein 2 and osteopontin (Ref 3). I said I could modify Caf1 to do the same and we could form it into hydrogels and grow 3D bone amongst other tissues – what could possibly go wrong. Funnily, the BBSRC did not agree and forbade any similar grant from darkening their doors for seven generations or something that sounded like that.

Try, try and try again

The project, such as it was, retreated to lick its wounds. At least my lack of citations meant that no one else in the world was likely to be working on it but neither it seemed was anyone interested in funding it. Salvation came in two forms. One was the MRC Industrial Collaboration studentship scheme, which enabled us to apply for money with Orla Protein Technologies Ltd, a spinout company I had co founded with Dale Athey in 2002. Orla sells engineered protein surface coatings such as those we used in the BMP/Osteopontin paper and very good they are too, try them yourselves at www.orlaproteins.com!

The second bit of luck was that Ana Roque applied for the studentship. She is an amazingly tenacious and hardworking scientist who single handedly made the Caf1 project work. First she tackled the ridiculously large Caf1 plasmid and won. We then had a manageable system that could produce mutant Caf1 in good amounts.

Y pestis

Immunoelectron microscopy of Y. pestis showing macrophage resistant hydrogel capsule From Du Y et al. Infect. Immun. 2002;70:1453-1460

She then showed that cells were not keen on growing on Caf1 surfaces. Not good. What turned it around was that by simply adding an RGDS motif we could make Caf1 act like fibronectin with cells sticking to it like last night’s pigs trotters.  Caf1 makes a macrophage resistant hydrogel capsule around the Y. pestis cell that prevents interaction with cells (see figure).  Ana had thus shown that it keeps its non-adhesive properties in vitro… whoo-hoo!. Thus, Caf1 is a non-stick, tough, flexible, polymer – all things very difficult to build into a protein by design. It can be genetically modified to imitate at least one Extra Cellular Matrix (ECM) protein and physically resembles many more. Ana then showed that we could cross-link it into hydrogels and her pièce de résistance was to show that we could make mixed polymers by expressing differently modified domains in the same cell and letting them mix randomly in the emerging polymer. This was published in Advanced Materials (Ref 4), which will do nicely as one of my REF papers although I am not waiting for the citations to roll in any time soon.

Caf1 hydrogel

Ana returned to Portugal and the Caf1 project was halted again. We got some short term funding to pay Helen Waller’s salary to make more protein and more mutants.

CatalystIn November 2013 the Technology Strategy Board (TSB – now Innovate UK) announced the Industrial Biotechnology Catalyst with £20M in the first round. Although I have been involved with the bioprocessing industry for many years I did not think the Catalyst was for me, as it seemed to be either biopharmaceuticals or bioenergy. However, I read the outline for the feasibility awards and it seemed to fit Caf1. I was thinking of a post doc for three years etc but the award size started at £2M, so some imagination was required. This led to the current project.  Protein engineering to design and produce new polymers will be done in my laboratory. This will be done by Helen Waller and a new post-doc. David Fulton will employ another post-doc to make our cross-linked hydrogels smart and responsive to a range of stimuli like temperature, light and pH.  Matt German will use impressive kit like his Atomic Force Microscope (AFM) to measure the material properties of the gels whilst Nick Reynolds will continue our work on wound care. Last, but not least, ICaMB blog’s very own Neil Perkins will work with another new post doc to understand how cells respond to and remodel the different materials. Neil’s suggestion that his qualification was that he was the first person I met that day is unfounded, the truth is that his title of Prof Gene Expression and Signalling fitted the number of words left in that section of the form (I maintain that the previous 2 people Jeremy had bumped into that day had turned him down – Neil).

To boldly go…

So, we have five years to turn Caf1 into a range of 3D cell culture products.  By exploiting bacterial production we hope to reduce costs and provide bulk materials at affordable prices for a series of applications. These will include research tools for cell culture, better culture conditions for industrial processes, tissue and regenerative engineering materials and many more.  I have produced products in the past and it is very different to our normal hypothesis driven discovery research. In discovering things about nature you generally have observed something and then set out to find out why it’s like that or how it works. In product invention you never know if it will ever work because, by definition, no one knows (and that is particularly true of protein engineering!). The Industrial Biotechnology Catalyst money is aimed at expanding the UK biotechnology industry and, in taking the money, we must be aware that quite justifiably the tax payer wants to see a return on the investment.  Ultimately we hope we can create jobs in a new area based upon this project.  What’s more, collaborating across disciplines to invent amazing new materials and use them to cure disease is a great way to spend ones working life.

[1] Soliakov A, Harris JR, Watkinson A, Lakey JH. The structure of Yersinia pestis Caf1 polymer in free and adjuvant bound states. Vaccine. 2010;28:5746-54.

[2] Orengo CA, Jones DT, Thornton JM. Protein superfamilies and domain superfolds. Nature. 1994;372:631-4.

[3] Mitchell EA, Chaffey BT, McCaskie AW, Lakey JH, Birch MA. Controlled spatial and conformational display of immobilised bone morphogenetic protein-2 and osteopontin signalling motifs regulates osteoblast adhesion and differentiation in vitro. BMC Biology. 2010;8:57.

[4] Roque AI, Soliakov A, Birch MA, Philips SR, Shah DS, Lakey JH. Reversible Non-Stick Behaviour of a Bacterial Protein Polymer Provides a Tuneable Molecular Mimic for Cell and Tissue Engineering. Advanced Materials. 2014;26:2704-9.

 

When Tom Williams went to Sci Foo Camp

In August, ICaMB‘s Tom Williams (a postdoc in Martin Embley’s lab) was invited to attend Sci Foo camp. Here he tells us all about it.

By Tom Williams

Dr Tom WIlliams

Dr Tom WIlliams

This is a post that’s been brewing for a while, since I returned from Google’s headquarters for the Sci Foo 2014 unconference last August. It’s taken the New Year cobweb cleansing (and an inopportune corridor collision with Neil) to get me to sit down and write it, but that’s also given me an opportunity to process and reflect on the sensory overload resulting from two-and-a-bit days of discussion, debate and near-constant mental stimulation I experienced last August in Mountain View.

First off, what’s an unconference, and what’s Sci Foo? Although they’re becoming more common in computing and technology-related fields, unconferences are still pretty rare in biology. They’re participant-driven conferences in which the attendees determine the programme on the fly — in our case, by hastily scribbling session ideas on pieces of paper stuck to a whiteboard!

sf_example

Creation of a Sci Foo conference programme

Sci Foo, which is organised by Digital Science, O’ Reilly Media (Foo stands for Friends of O’Reilly) and Google, is an annual, invitation-only science-themed unconference with participants from across the traditional scientific disciplines as well as science publishers and technologists. I’d heard about the event, but didn’t know much about it — and my first thought when the invitation email arrived was that the whole thing was a scam! Luckily for me it turned out to be genuine, and, with some financial support from ICaMB to cover my travel costs, I was bound for California at the beginning of August.

sci_foo_logo_sm

One of the things I’d noticed in the invitation was that Sci Foo was surprisingly short by usual conference standards – a day and a half of scheduled sessions, with an ice-breaker the night before. On arrival, the reason soon became clear – this was easily going to be the most intense, and intensely stimulating, meeting of my career. The range of backgrounds and perspectives among attendees proved to be hugely exciting, if more than a little daunting, and at the opening barbecue I found myself rapidly paring back my usual conference intro into something that musicians and videogame designers – let alone physicists – might find at least somewhat meaningful (Incidentally, this experience turned out to be very helpful for explaining my work to non-scientist friends and relations, and this Christmas may have been the first time I was properly able to explain to my in-laws what it is I actually do). I was struck not only by the breadth, but also the quality (and in many cases, the fame) of the other attendees, and began to wonder – not for the only time that weekend – why exactly I had been invited! This seemed to be a common feeling for many of the participants, and turned into a fairly reliable opening gambit with other less eminent members of the gathering over the following days.

It’s difficult to succinctly describe the mental atmosphere that developed at Sci Foo over the following two days. I’ve already referred to the intensity, but the freeform nature of the whole event, and the enormous diversity of the topics on offer were also key elements in the heady mix. I wasn’t necessarily learning all that much about my own field, nor was I really making contacts with potential scientific collaborators – the usual hallmarks of a successful conference – but I was being exposed to areas of inquiry which were entirely new to me, often by leaders in their respective fields, and the overall feeling was that of being a kid in an intellectual sweet shop.

Although I began by attending sessions on biology and evolution, I soon found that the most interesting experiences were to be found in sessions far outside my field of expertise. One early session that sticks out for me was a broad round-table discussion on new tools revolutionising different scientific fields. I spoke about how new sequencing technologies are allowing us to explore the world of uncultivated microbial diversity for the first time, and the impact this new data is having on our understanding of the tree of life. This was followed by Lawrence Krauss and Saul Perlmutter discussing techniques for detecting gravitational waves closer to the big bang than ever before, and the implications these findings might have for theories on the origin of the universe! This was one of several moments during the weekend when the links between research into biological and cosmological origins became very clear, and I began to lament my ignorance of physics – something I’m now working to at least partially correct through popular science.

Not all the sessions were quite so profound, even if they were interesting in many other ways. In one session, we put the results of the hilariously-titled 1997 paper “The experimental generation of interpersonal closeness” (Aran et al. 1997) to the test. Participants were paired up with strangers and given 45 minutes to discuss a series of questions designed to promote feelings of warmth and familiarity. The procedure worked oddly well, and a general feeling of scepticism in the room soon gave way to laughing, joking and free-flowing conversation – a palpable drinks-reception atmosphere without the booze. Neither I nor my randomly-assigned partner – a Scandinavian biochemist – were immune to the effects, and a genuinely weird feeling of intimacy had developed by the end of the session. The questions seemed to work by leading participants from standard small-talk, through topics of gradually increasing intimacy, to questions about deeply-held values and philosophical perspectives,  condensing the normal development of a friendship (or courtship) into a single sitting. The experience raised interesting questions about how easily our emotions and perception can be manipulated, and the session ended with a stimulating discussion; it wouldn’t surprise me if some of those nascent relationships were continued more discreetly elsewhere!

Some of the sessions were more closely related to my own research interests. I’m a keen advocate of open data, and I typically upload the datasets associated with my papers to repositories such as Dryad and figshare.  So it was really interesting to meet up with Chris George and other members of the figshare team to share experiences and discuss the future of scientific communication. Everyone agreed this was going to involve more transparency in terms of publishing raw data and negative results, and we discussed the necessity of new algorithms for filtering and making sense of the resulting data deluge. Most of the participants were computer scientists or, like me, computationally-inclined biologists, though, for whom data availability and re-use – especially of other people’s data – is almost always a good thing, and I wonder if more traditional wet-lab biologists would have been quite so unanimous in their agreement.

There was also much to enjoy at Sci Foo that was just plain awesome. Andy Carol‘s functional LEGO recreations of famous computing machines – from Babbage’s Difference Engine  to the Antikythera Mechanism of Ancient Greece – ranked very highly among these, as did the beautiful “nanoflights” (stop-motion films based on scanning electron microscopy) of Stefan Diller

Greta Ruessel_nah

The proboscis of the glasswinged butterfly, Greta oto; a nanoflight still by S. Diller, http://www.nanoflight.info/.
Drosophila, S. Diller, www.electronmicropscopy.info 2015

 

This mix of art, fun, discussion and synthesis across so many different disciplines felt really unique and perhaps best captured the feel of Sci Foo for me. Unconferences like Sci Foo are very different from the usual academic conference, and while I found that freshness to be enormously stimulating, the lack of formal structure also posed a number of challenges. I think it partially depends on how extroverted you are: I’ve grown used to the semi-formal setting of a talk or poster session, where the roles of presenter and audience member, and the times for discussion, are much more clearly defined. Unconferences demand and reward participation: you may have to drag yourself out of your own shell, but the outcomes are ultimately very worthwhile; at the same time, Sci Foo is clearly an environment in which “alpha academics” will thrive from the off! Overall, I had a fantastic time at SciFoo and the unconference experience is one that I’d unreservedly recommend to any scientist. A quick Google search will turn up a number of upcoming unconferences in the UK, most of which are open to anyone, although they tend to be on tech-related topics. Still, it might be an interesting structure to consider when organising future away days or postgrad conferences…

REF 2014: Hurrah, we did really well – but is it really a good exercise?

By Neil Perkins

And so the REF 2014 results are upon us. If you listen closely you can hear academics all around the country trying desperately to find the method of expressing the results that most favours their own Institution (or downplays bitter rivals). Of course, this is a technique commonly used in publishing research articles so there is a lot of expertise in this area.

Anyway, however you wrangle the figures in ICaMB we think we’ve done pretty well (whisper it quietly, possibly better that we expected when our return was submitted).

Most ICaMB scientists went into UoA5 Biological Sciences, although a number of us also were included in the UoA1 (Clinical Medicine) and UoA3 (Allied Health Professions, Dentistry, Nursing and Pharmacy) submissions. In fact UoA5 contained only ICaMB members and was written and submitted by ICaMB members. So this is the right place to say congratulations to ICaMBs Professor Brian Morgan who masterminded, with the help of Amanda Temby, our UoA5 submission. We hope Brian has recovered from the ordeal by now.

So how did we do? If we go by the Times Higher Education table then Newcastle (i.e. ICaMB) came joint 5th overall. However, in the clearly much more important ‘Output’ table we come 2nd in the country!! I suspect that’s the one that will end up on the front page of our website. Our ‘Impact’ submissions dragged us down a bit. I remember the meetings where we struggled with the tight definition used for ‘Impact’, something not easy for an Institute that really focuses on fundamental science. We work on important and relevant subjects but the impact of this on medicine or biotechnology is often a few steps removed.

THE ranking

The Time Higher Education raking for Uo5, Biological Sciences. The most important section (cough) is highlighted.

It would be remiss of me not to point out that our sister UoA submissions in Newcastle also did well

UoA1 Clinical Medicine) came 9th out of 31, UoA3 (Allied Health Professions, Dentistry, Nursing and Pharmacy) was 15th out of 94 while Uo4 (Psychology, Psychiatry and Neuroscience was 9th out of 82.

Lies, damned lies and…..

I like this viewer put together by City University London

http://www.staff.city.ac.uk/~jwo/refviewer/ 

And if I tweak the parameters in just the right way……

Second again

……. Hurrah! Second again!

A big BUT

OK, if we were to be slightly self-critical it could be noted that our Uo5 submission had, relative to many Institutions, a relatively low number of staff associated with it, although this is the substantial majority of the people in ICaMB. It was very much the ICaMB submission, with many others in the Faculty of which we are a part, going into UoA1, Clinical Medicine.

However, this is also an exercise in who decodes the rules most successfully (and there was head scratching at times over ambiguities and what it really meant). So what better time, after having done well, so it cannot be said to be sour grapes, to repeat that the REF really is a bad way to go about assessing the relative research strengths of UK universities. The arguments for why this is the case have been aired before in detail (also here) and I will not go over them all again here. I think that every academic I speak with agrees with this. People involved with this work phenomenally hard at all levels in the university but it has to be said that it is a colossal, time consuming juggernaut of dubious worth.  Speaking to colleagues who were members of REF panels, I was horrified at just how many papers they were expected to read. You do not need to go that far outside my area of expertise before my judgement becomes quite superficial. Quite how anyone thinks this process leads to an unequivocal assessment of research quality is beyond me. However, as an entire industry seems to have grown up around the REF, incentives for change are few.

So what could replace it? Well as academics we are judged and assessed continually as part of or our normal jobs. Our grant applications are rigorously reviewed. Our papers are refereed in detail. There are citation indices and download statistics showing if these are actually being read. While individual applications or submissions are subject to some randomness, over an Institution, over time, these are the measures that really assess how well we are doing. The information for these is already out there and would be relatively quick to compile.

Of course there are caveats to this. Different disciplines receive different levels of funding or are cited lightly relative to others. But it should not be beyond the wit of the academic community to come up with different weightings for different subject areas. Wouldn’t it be refreshing if someone at the top came out and said, ‘never again, there has to be a better way of doing this’. However, I suspect this might be wishful thinking. I’ll just fearfully wait for the email saying “Neil, about REF 2020, Brian did a great job last time and we’d really like it if you could…..”

The opinions expressed in this article are those of the author and do not reflect those of Newcastle University

Recruiting the next generation of ICaMB scientists

In 2013, we created the IRES fellowship scheme to recruit potential new Principal Investigators to ICaMB. Now Faculty wide and renamed the Newcastle University Research Fellowships (NURFs) a new round of recruitment has just opened. Here, Neil Perkins reflects on the thinking behind the IRES scheme and why recruitment of early career researchers is so crucial.

ICaMBatNewcastle NURF advert final

It’s a moment for sober reflection when you realise that you can no longer be classified as a ‘young scientist’ and have now become part of a problematic group of rapidly ageing professors. Although when Bob Lightowlers, the ICaMB Director, told us a few years ago that we only had one Principal Investigator (PI) under the age of 40 I think we were all a bit shocked.  Only one? Speaking as one of that cohort of over 40’s, I would of course defend our ability to still perform cutting edge science and stay on top of the latest developments in technology and social media. Well some of us anyway. However, as with many things, balance is important. Early career (to use the formal term) PIs bring vibrancy and energy to a department, generate new ideas and very importantly also challenge ingrained departmental behaviour. At least that’s how I like to fondly remember my time as a new PI in Dundee. I was probably just a pain in the neck.

To get back to the point, we had a problem and needed to find a way to fix it. In an act of skilful diplomacy, Bob Lightowlers managed to persuade the faculty leadership that we could begin the process of new recruitment immediately and that this would be funded by proleptic appointments. Yes, I had to go and look that up when I first heard it (after nodding my head as if I knew what he was talking about). In practical terms this meant that because we could anticipate retirements in future years, this future funding stream would be used to create new positions now. I assume the numbers add up.

We wanted to do something different with these new positions. In recent years, fellowships have become an increasingly popular mechanism to kick start someone’s career as a PI. They offer a transition period, where the new PI is protected from too onerous a teaching load (although all our new appointments will do some teaching), enabling them to focus on establishing an independent research programme. From the perspective of management, they provide the opportunity to assess whether a new appointee is really suited to this career before being offered a permanent position.  So at the beginning of 2013 we created the Independent Researcher Establishment Scheme (or IRES). In the first instance this involved the creation of three 5-year fellowships.  Importantly, after a rigorous assessment period, these should all lead to full academic positions with open contracts. It should be emphasised that there is no element of competition between our new IRES fellows (apart from some hopefully friendly rivalry).  We want them all to succeed and get permanent positions.

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When it came to recruiting the IRES fellows we were very conscious of the fact that we were recruiting future colleagues so we wanted to do more than the fashion parade that often passes for the interview process for new lecturer appointments at some UK universities (see rant to the right). We had 80 applications for the 3 IRES positions, many of which were of a very high standard. From this, after some heated debate by the ICaMB Research Committee, we whittled this down to a list of ten, all of whom were invited to Newcastle for an informal visit, where they gave a seminar, met colleagues and participated in a ’round table’ discussion about their future research and funding plans. We took them out to dinner and put them up in a hotel. Not quite the full Philip Cohen Dundee bird watching experience but a step in the right direction I think. From this list of 10 we created a final short list of 6, who all returned for a formal interview and from these we appointed 3 IRES fellows. All our IRES fellows are now in place and you can read about who we appointed here, in a previous ICAMBlog post. Will it work? Only time will tell but the early signs are very promising. We are very proud that our first arrival, Owen Davies, was recently awarded a prestigious Royal Society/Wellcome Trust Henry Dale Fellowship (more on this in the future). Our IRES appointments also join our growing cohort of successful early career PIs that includes Paula Salgado (recently awarded an MRC New Investigator Research Grant), Kevin Waldron (also recipient of a Royal Society Henry Dale Fellowship), Yulia Yezenkova (Royal Society University Research Fellowship), Suzanne Madgwick (Wellcome Trust Career Re-entry Fellow), Heath Murray (Royal Society University Research Fellow), Joao Passos (BBSRC David Phillips Fellowship) and Claudia Schneider (Royal Society University Research Fellow). I was very happy to hear that they had recently arranged a trip to the pub to begin the process of plotting and scheming.

The author, in his youth, plotting and scheming with other new Dundee PIs in our traditional meeting place.
The author (3rd from left), in his youth, plotting and scheming with other new Dundee PIs in our traditional meeting place.

Imitation is the sincerest form of flattery, although not to be encouraged in undergraduate essays or academic publications, and now the ICaMB IRES scheme has been transformed into the Newcastle University Research Fellowships. Essentially, with some tweaking, our IRES fellowships have now been adopted by the entire Faculty of Medicine in Newcastle. Despite this, recruitment will still be handled by the Institutes themselves, so if you are reading this and are interested in becoming an ICaMB PI, then please get in touch. Here is our advert (ICaMBatNewcastle NURF advert final – pdf) and informal enquiries may be made to:

Bob Lightowlers, Institute Director (robert.lightowlers@ncl.ac.uk)

Janet Quinn, Search Committee (janet.quinn@ncl.ac.uk)

Kevin Waldron, Institute Fellowship Advisor (kevin.waldron@ncl.ac.uk)

Importantly, ICaMB is committed to the Athena SWAN Charter for women in science as detailed on our web site.

Football text box

The opinions in this article are those of the author and not necessarily those of ICaMB or the Faculty of Medical Sciences at Newcastle University. Although the author thinks they really should be. 

One year of the ICaMBlog in numbers

By Neil Perkins

At the one year anniversary of the ICaMB Blog, and after publishing 35 articles, it seemed like a good time to reflect on what this initiative has (or has not) achieved. When Paula Salgado, Phil Aldridge and myself (with the prompting and encouragement of Bob Lightowlers) started this, there were a number of very clear goals we had in mind.  The first of these was to improve communication within ICaMB itself, so that we would all have a better sense of what our colleagues were up to, their achievements and to introduce new PIs.  In particular we wanted to highlight some of the great things our newly formed postdoc and PhD student associations (IPA and PANIC) have been doing. We also wanted to tell the world about some of the exciting science being performed in ICaMB and highlight some issues and discoveries that we thought would be of wide interest.  Finally we wanted to show the fun side of being a scientist in Newcastle and reveal some of what we get up to when we’re not in the lab.

Did we succeed?  Well that’s probably not for us to judge and the true test of this will be if the blog is still going in five years time (and if people are still reading it).  However, one unanticipated highlight for me has been the discovery of Google Analytics and what it can tell us about the success of the ICAMBlog. As a hard core geeky scientist, Google Analytics can be frighteningly addictive. A guilty pleasure for me has been to watch in real time what happens after we start publicising the latest blog: as soon as the emails get sent out, the tweets are sent or the Facebook update posted you can see people logging in to read the blog.  We don’t know who you are but we can see where you are and how you found us. Fascinating and slightly scary.

Each spike on the graph represents people viewing the website when a new blog article comes out. There is an immediate response the moment we send out an email, tweet or share on Facebook. Data shown is from Sept 1st - Dec 31st, 2013

So for this blog, to commemorate our one year anniversary, I thought I’d share some of the numbers. How many of you actually read the ICAMBlog?  Where are you from? Which article was the most popular?

So how popular are we?

At the time of writing we have had 7,703 ‘Unique Visitors’ to the blog, who have made 11,715 visits comprising a total of 20,602 ‘Page views’.  Unique visitors really means different devices, so someone who accesses the blog through their phone as well as a computer will count twice.  On the whole though, we are pretty happy with this.  It is thousands of people who now hopefully know more about ICaMB and what we do than a year ago.

So where is everyone coming from who reads the blog?  Unsurprisingly, the majority of our readers (58%) come from the UK.  The USA and Canada are the next highest, (although see the ‘reddit event’ below), followed by Australia and India.  Although the numbers are lower for other countries, the readership is truly global.

Within the UK, as might be expected, we have a large number of readers from the Northeast.  Readers from Newcastle upon Tyne represent 38.5% of our total readership which means that >60% of our readers are not local, so we are achieving our aim of getting the word out there.  London is the next highest city followed by several other cities with strong university links.

Someone from San Francisco just started reading the blog

What are people reading?

Our most popular article by far has been ‘Exploding Bacteria for Science’, which featured the work of Kenn Gerdes from the Centre for Bacterial Cell Biology here in ICAMB. This article garnered 3,189  page views, 15.5% of our total (note to blog team, must feature more exploding things next year). However, this number may be slightly artificial as it benefited from exposure on reddit (see what that means below). Our first ever long feature was ‘Bulging Bacteria and the Origins of Life’ which highlighted an outstanding Cell paper from the Errington lab on L-form bacteria. This is particularly impressive as the blog was starting and it wasn’t on people’s radar yet.  Completing our top 5 were the blog on ICaMB PhD student opportunities, the ‘Great Bacterial Bake Off‘ and ‘ICaMB goes away for the day’.

The success of Exploding Bacteria is also reflected in the number of views on our ICaMB Youtube site, with 3,186 visits to the penicillin effect video associated with this article.  Jeff Errington’s Bulging Bacteria video follows, with 322 views and the video of Jeremy Lakey and a new bacterial cell killer had a respectable 187 views, completing our top 3 video chart.

Are they really reading these articles?

One interesting feature of Google Analytics is that we can see how long people stay on each page, although we cannot control for people opening the page and then wandering off to do something else.

So when people from England and Wales log on, they spend an average of 1 minute 51 seconds with the page open.  They may be making tea of course but in general this suggests they are reading the blog.  Readers from Scotland and Northern Ireland, slightly less impressive, with 58 seconds and 1 minute 7 seconds respectively. Maybe they are speed-readers in Scotland.

When we look deeper, some of those page view numbers start to look a bit less impressive. All those visitors from the USA don’t look so good when you realise they stayed on the page for an average of 13 seconds.  Low attention span maybe?  It’s OK to say that, they will not have read this far down the page. Canada is a bit better at 34 seconds, Australia is at 24 seconds but India is a very respectable 1 minute 25 seconds. People from Newcastle spend 2 minutes 11 seconds on each page. London less so at 46 seconds while other cities average around 30 seconds.

Our headline numbers also start to look a bit less impressive when we take visit duration into account.  Of our 20,723 page views, 9,669 are for less than 10 seconds.  But that still leaves >8,000 page views being read properly. So a bit of a mixed bag but at least our colleagues seem to be interested in what we are writing.

The impact of social media

To get word of the blog to the outside world we have been using Twitter, Facebook and other forms of social media.  Google Analytics can also tell us how successful this has been. Of our 11,715 visits to the site, 1,284 have been through Twitter and 1,105 through Facebook. Twitter visitors stay for 1 minute 14 seconds on the site, while Facebook visitors stay for 49 seconds.

The reddit event

Reddit is a ‘a social news and entertainment website where registered users submit content in the form of links or text posts’.  Paula sometimes submits links to the science section when the ICAMBlog is carrying something that we think might be of interest.  This was certainly case with ‘Exploding Bacteria for Science’, which picked up a lot of traffic from reddit, accounting in part for its high popularity.  In total, we have had 1,557 visitors come through reddit and another 488 through Stumbleupon (‘a form of web search engine that finds and recommends web content to its users’).  These account for quite a large chunk of our USA traffic to the site. The down side is that the average visit duration of a Reddit user is 3 seconds, while someone from Stumbleupon lasts for 9 seconds.  I’m going to go out on a limb here and suggest that they are not actually reading the content.  So the moral is that while some approaches can boost our overall numbers, it is whether they stay around and actually read the articles that is important.

That big spike is people coming to the blog from reddit, staying 3 seconds and then leaving. The smaller spikes are our normal readership levels

Any Conclusions?

So have we been a success?  We think so but there is clearly a lot of room for improvement and scope to increase our readership. In the year ahead we certainly plan to continue our work on the blog and are very happy to welcome Suzanne Madgwick and Kevin Waldron to the blog team.  We will continue to highlight the science being produced in Newcastle but are thinking of broadening the scope of our articles.  For example, should we publish more opinion pieces and take a stand on the various issues confronting scientists today, both in and outside ICaMB?  We’d be very interested in hearing from you to let us know what you think. Comment is easy: tell us what you think and submit, no need to register or create an account. We would really like to hear from you, the reader that spends some time with us and reads all the way to end  – what kind of articles would you be interested in reading? Let us know!

A final word.  Those of us on the blog team would like to thank Phil Aldridge for all his help over the last year.  Phil has decided to step down from the blog after this first year but his input and enthusiasm has been crucial to getting things going and keeping the momentum up. Thanks Phil!