How a motile cytoskeleton drives bacterial cell division

seamusIn a recent issue of Science, the discovery of a key mechanism for bacterial cell division was reported. This work was carried out by Dr Seamus Holden’s lab (ICaMB) in collaboration with Professor Cees Dekker (TU Delft), Professor Yves Brun (Indiana University), Professor Mike VanNieuwenhze (Indiana University) and Professor Ethan Garner (Harvard University). Here, Seamus tells us about this discovery and what its implications could be for antimicrobial research.

Bacterial cell division is a lovely mechanistic problem in biology: how do the simplest living organisms build a crosswall at mid cell, against very high outwards pressure (think of a racing bike tyre), without bursting?  A ring of protein filaments forms around the future division site, and enzymes associated with this ring build a new crosswall that cleaves the bacteria in half. But what has remained completely mysterious is how these proteins work together as a single nanoscale machine to cut the bacterial balloon skin (cell wall) in two.

Cytoskeletal proteins FtsZ in live bacteria imaged in vertical nanocages

Cytoskeletal proteins FtsZ in live bacteria imaged in vertical nanocages

Working together with collaborators in Delft, Indiana and Harvard, we tracked the organization and motion of key division proteins as they build the dividing crosswall, and the organization of the newly built crosswall itself. We began by examining the motion of FtsZ, a cytoskeletal filament that is required for cell division – cytokinesis – in bacteria and is related to the tubulin cytoskeletal protein found in eukaryotic cells. Using high-resolution microscopy techniques, we found that FtsZ filaments move around the division site, traveling around the division ring. We imaged the motion of individual cell wall synthesis enzymes, and saw that the synthesis enzymes ride on FtsZ filaments, building new cell wall as they travel along the division site. This causes the cell wall to be synthesized in discrete sites that travel around the division site during cytokinesis, a process which we were able to observe directly by using dyes that label the bacterial cell wall. Using a variety of experimental techniques, we were able to speed up or slow down how fast FtsZ rotated around the cell. Strikingly, we found that the speed of FtsZ filament motion determines how fast the cell can divide. When FtsZ moves more rapidly, cell wall is produced more quickly, and cytokinesis happens faster. This shows that the motion of FtsZ is the critical overall controller of cell division.

One challenge that we faced was trying to look at the division proteins in actively dividing cells. At the earliest stages of division, it was possible to image division protein organization because the proteins in the partially assembled ring are sparsely distributed. However, a new strategy was required to measure how the dense protein network of actively dividing cells was organized. Normally, bacteria are immobilized flat on a microscope slide, and imaged from underneath, but unfortunately this places the division ring side-on, obscuring the motion and organization of division proteins. To solve this problem, we used nanofabrication technology, originally developed to manufacture computer chips, to create tiny gel nanocages to trap bacteria in an upright position.

Bacteria trapped in vertical nanocages

Bacteria trapped in vertical nanocages

By trapping individual bacteria upright, we were able to rotate the cell division ring so that it was fully visible on our high resolution microscope. This revealed the dynamic motion of FtsZ filaments as they travel around the entire division site:

Together, these results revealed the basic mechanistic principles of bacterial cell division: that the building of the division crosswall is orchestrated by moving cytoskeletal filaments.  Previously, the cytoskeleton was thought to serve as a static scaffold, recruiting other molecules and perhaps exerting some force to divide the cell. This new work demonstrates that all the components of cell division are in constant, controlled motion around the division site, driven by the fundamental dynamics of the cytoskeleton.

In the longer term, this study could open up novel antibiotic targets. Based on the discovery that the treadmilling motion of the bacterial cytoskeleton is critical for division, it may be possible to develop new drugs that specifically inhibit this motion, similar to how the chemotherapy drug taxol suppresses the motion of the cytoskeleton in cancer cells.

==================================

Links

Explanatory animation: https://youtu.be/6dq2_gqKPfU (Animation credit TU Delft / Scixel)

Nanocage Video: nanocage-movie-2.

Science report: http://science.sciencemag.org/content/355/6326/739

Press release: http://bit.ly/2kwsnJf

Any excuse to drink red wine

By Elisabeth Lowe

I’m writing this blog from an interesting perspective – though a member of the lab I’m not involved in the project, except through the (exhaustive!) discussions at coffee time with Harry Gilbert and the rest of the authors on the paper. This work, published today in Nature, describes the way in which one particular species of human gut bacteria is able to degrade a complex plant polysaccharide. Why is this new, you might well ask? Well, after being talked to death on the project, so much so I’d be glad never to hear a word about it again, I’ve actually come to appreciate what a great piece of work it is. The Bolam and Gilbert labs have published quite a bit on plant polysaccharide degradation over the years, but this one is a little different, because the polysaccharide involved – Rhamnogalacturonan-II (RGII) – is thought to be the most complex glycan found in nature. It contains ~13 different sugars linked by 21 different linkages, and all but one can be broken by a single bacterial species, Bacteroides thetaiotaomicron (Bt).

Complex structure of RG-II from red wine

Complex structure of RG-II from red wine

Wade Abbott, a post-doc in Harry’s lab when he was at the Complex Carbohydrate Research Centre, in Athens, Georgia, which is incidentally where the structure of RG-II was determined in the first place by Alan Darvil and Malcolm O’Neill in the 1980s, initiated this project. We knew which loci were upregulated during growth on RG-II from earlier work by myself, Dave Bolam and Eric Martens, so Wade set about cloning and expressing the 30 genes in these loci, and looking for activity with a PhD student, Jeff Xhang. It was a tough job, and little progress was made. When Harry came back to the UK he decided he absolutely had to crack it, and put two post-docs onto the project, Art Rogowski and Didier Ndeh. Though as the project has progressed, more and more people from the lab were sucked in, including the post-docs Alan Cartmell and Aurore Labourel, and Harry’s last PhD student, Ana Sofia Luis. All worked incredibly hard, assisted by Arnaud Baslé from SBL, and between them discovered the activities of 26 enzymes, including seven entirely new glycoside hydrolase families, three new activities, and seven crystal structures, with all the active site mutations, and ligand soaks that go along with a new crystal structure.

Working out the enzyme activities on a polysaccharide as complex as RG-II poses some problems, in that you can’t really buy it, so you have to make it. RGII is concentrated in red wine, so Harry put 150 litres of Asda’s not so finest wine on Dave Bolam’s credit card (don’t ask) and with Art and Didier, took it to Prozomix in Haltwhistle, to use their industrial concentrators.

Concentrating wine

Starting to concentrate 150 L of wine

As you can see, this did not end well.

It's all gone horribly wrong

It’s all gone horribly wrong

 

Art then turned to apple concentrate and managed to purify some through an intensive multiple two-week process. Making or buying oligosaccharides is also extremely difficult, so Didier devised a way of killing two birds with one stone – identifying which unknown open reading frames (ORFs) were enzymes, and making oligos at the same time. By deleting the gene of interest, RG-II degradation (which is mainly exo-acting) was halted at the point at which that enzyme acted. Taking the supernatant from these strains grown on RG-II and purifying the sugars released by the bacterium yielded partial breakdown products which could be identified by mass spectrometry with tremendous help from Joe Gray, and then used as a substrate for the enzyme in question.

Getting the data in a format suitable for the tight space restrictions imposed by Nature was almost as challenging as doing the work. Given that Harry is not very artistic, and certainly has no idea how to use Adobe Illustrator, he was fortunate to have three talented artists Ana, Art and Aurore, who ended up doing all the figures. They are now referred to as the art department. This project was definitely a labour of love (for Harry, if no-one else!) and by carefully characterising the breakdown of this polysaccharide, one linkage at a time, has actually revealed new features of the structure of this critical plant polysaccharide. Finding and characterising the vast repertoire of enzymes produced by gut microbes is not only interesting in its own right, but can provide tools to understand complex glycan structure. It’s a fantastic achievement, and I pity the poor lab member who has to try and bake the RG-II cake for the celebrations this week!

 

Link to paper

 

Essential metals for crystallographers: copper, gallium and a lot of gold

As the Newcastle Structural Biology lab, prepares to enter a new era with a fantastic state-of-the-art new in house X-ray system, we asked Rick to give everyone a perspective of the last 14 years of Protein Crystallography in Newcastle on behalf of all of us – Arnaud, Martin, Jane, Paula, Bert, Owen and Jon

by Prof Rick Lewis

A little over 20 years after von Laue, Friedrich and Knipping collected the first X-ray diffraction experiments on copper sulphate in 1912, Bernal and Hodgkin conducted the first macromolecular crystallography experiments – on pepsin, which was first crystallised by Northrop in 1928. These, and other early pioneers (including father-and-son Nobel laureates WH and WL Bragg), established the principles by which Kendrew and Perutz solved the first 3-D protein structures, myoglobin and haemoglobin, in 1958 and 1959.

If we fast-forward more than 40 years to the RAE2001, and a stated ambition for the immediate predecessor of ICaMB was to establish a protein crystallography group in Newcastle – I think it fair to say the the University was a little slow to recognise the value of structural biology!

Steven Hardwick was so excited at the lab’s opening in 2003 that he fell asleep

Nonetheless, the Director at the time, Monica Hughes, notably aided and abetted by Steve Yeaman, Jeremy Lakey, Bernard Connolly and Harry Gilbert, coerced the powers-that-be to dig behind the sofa for some loose change and, to cut a long story short, the Newcastle Structural Biology lab (NSBL) was born in 2003.

 

 

Rick preparing to shoot some crystals in the brand new kit back in 2004

Rick preparing to shoot some crystals in the brand new kit back in 2004

Back then, there were just two prime users of the X-ray diffractometer, my group and that of Mark Banfield (who left for the John Innes in 2008). Mark’s departure opened up an opportunity for Susan Firbank to establish her own research group, which in turn meant that Arnaud Baslé replaced Susan as the X-ray facility manager. In between Susan’s sudden departure in 2011 for a new life as a pharmacist, our colleagues in NICR, Martin Noble and Jane Endicott  were recruited to NICR. Paula Salgado arrived in 2012, Bert van den Berg and Owen Davies in 2013, and Jon Marles-Wright, whose beatific face used to light up the hoardings around the INTO building site, reappeared (after a sojourn up in Edinburgh) in Biology in 2016. In 6 years, the NSBL grew from a single PI to seven, plus Arnaud. The active user group now comprises well over 30 names.

In 2015, the University announced it had set up the Research Infrastructure Fund (RIF), a £31M pot of gold to which like-minded groups could apply for funds for new equipment and other essential infrastructure. To be honest, the RIF had passed under all our radars, and we were first alerted to it by a small molecule crystallographer in Chemistry. We put together what we thought was a strong case and were very pleased to hear just before Christmas 2015 that our bid was successful. Ironically, our colleague in Chemistry’s application to the same round was, ahem, unsuccessful, but a big hand to Mike for the heads-up!

Bye bye Miss Inverted Phi*: a proper farewell to the long serving old generator (*with apologies to Don Mclean)

So a year later, after a period of testing and comparing different options and going through a remarkably painless procurement procedure, we serenaded the final shut-down of the 13-year old X-ray equipment over a glass of prosecco. Bert and Martyna both won prizes for guessing closest how many operational hours (>95,000) the old generator had clocked up. The floor in the X-ray lab was relaid (humble apologies for the noise and the smell…) and we have just installed our brand new box-of-tricks.

So what do you get these days for a little under a million pounds? Not only a state-of-the-art X-ray detector, but a revolutionary new X-ray source. Instead of firing electrons at a rotating copper drum to generate X-rays, the new X-ray source relies upon the application of an electric current across a jet of liquid gallium, to produce an X-ray beam with the best spectral characteristics and intensity in the market place. Allegedly.

Almost ready to start shooting crystals!

Arnie, our new X-ray system, almost ready to start shooting those crystals!

Moreover, we have been early adopters of this brand new technology – in fact we are the first and currently only UK group with such an instrument! Exciting times indeed.

The upshot is a 100-fold improvement in performance. Data sets that would take an entire weekend to collect can now be done in 20 minutes, about what it would have taken to collect just a single image with the old system. The final piece of the jigsaw is expected in the late spring, when a sample changer will be installed. This robotic slave will allow us to load up 48 samples into a dewar of liquid nitrogen for the programmed sample changer to load one at a time onto the X-ray machine, take test exposures, rank sample quality, and then go back and collect full data sets on the best crystals. All of this without any user intervention. Amazing. If you’d told me back in 2003 that we would have this capability in-house before both Bernard and Harry had retired, I’d have laughed out loud….

Origins of life in Newcastle

ICaMB’s Prof Jeff Errington organised and hosted an impromptu symposium on the origins of life at the Centre for Bacterial Cell Biology (CBCB) on Wednesday 18th January 2017. About 80 people attended, hearing 11 talks from a mixture of Newcastle and international speakers, including a number of guests who had travelled over from Japan for the meeting. The program was arranged more or less in “chronological” order, starting with the origins of the solar system 4-6 billion years ago, and ending (still almost 2 billion years in the past) with the emergence of the eukaryotes. The meeting sparked several very lively discussions, perhaps reflecting the difficulty of doing standard hypothetico-deductive experiments on the topic, in the absence of time travel technology! Nevertheless, the day was a great success and is likely to lead to new international collaborations and funding opportunities.

By Jeff Errington

My emerging interest in the subject has two origins. First, through ageing and trying to find a reason for existence before existence disappears! Second, the lab’s work on L-form bacteria (see Box), which has attracted much interest from the origins of life scientific community.

L-form bacteria use a seemingly primitve mechanism of replication.

L-form bacteria use a seemingly primitive mechanism of replication. L-forms are cell wall deficient bacteria, which turn out to replicate by a slightly bizarre, seemingly haphazard mechanism involving membrane blebbing and tubulation. The process provides a model for how primitive life may have proliferated billions of years ago, before the invention of the cell wall.

 

The latest findings have led to a number of fascinating new scientific contacts, and about a year ago, Prof Shige Maruyama, who heads a major Japanese research institute dedicated to origins of life work called the Earth-Life Science Institute (ELSI), made contact, proposing discussion around possible collaborations. After a series of small meetings in Newcastle and my visit to Tokyo, momentum began to emerge, culminating with the proposal for a major workshop in Newcastle, with half a dozen or so ELSI members planning to attend.

Prof Shige Maruyama, ELSI, Tokyo, Japan

Prof Shige Maruyama, ELSI, Tokyo, Japan

As discussions developed, I identified various experts in Newcastle with complementary expertise and interests in the general area, and the idea for a full blown symposium took shape. There was even time to identify a top class international “guest” speaker, Prof Bill Martin from Dusseldorf, who came over at short notice to give the concluding talk.

This is not the place to go through each talk in detail. However, from my perspective, what I hope people took away from the meeting would have included the following general points.

First, the problem is amazingly multidisciplinary, with important contributions from astrophysicists, geochemists, organic chemists, microbiologists (structure/function, metabolism and physiology) and evolutionary bioinformaticians. Second, we still have a very hazy understanding of many of the early events in the earth’s planetary history, e.g. when did the water arrive and how much? Third, it is clear that microbes were responsible for huge changes in planetary chemistry, particularly oxygenation but also that planetary composition must have reciprocally influenced microbial evolution.

Prof Bill Martin, Dusseldorf, Germany

Prof Bill Martin, Dusseldorf, Germany

The day concluded with a very nice dinner at the Jesmond Dene House Hotel, supported by Newcastle University and hosted by Pro-Vice Chancellor Prof Nick Wright. I’m sure that the original owner of the house, Lord Armstrong, would have approved of the day (for example, I gather that his company won the contract to build ships for the Japanese Navy 120 or so years ago). I’m also sure that as a Fellow of the Royal Society (elected in 1843) he would have been acquainted with Charles Darwin and perhaps they too had interesting conversations about the origins of life in their own time frame.

Muhammad Ali, sepsis and antibiotic resistant superbugs

by Jeff Errington, in collaboration with Paula Salgado

I’m old enough to have watched in awe Muhammed Ali’s incredible exploits in the boxing ring, and his always entertaining and thought provoking, sometimes bizarre, TV interviews and clips. Most would agree that he was an amazing, inspirational human being.
Like many millions of people around the world, I was devastated to hear of his sudden passing. I watched a wonderful documentary on TV and read several articles about his amazing life on line. As a microbiologist, one seemingly throw away line caught my attention: cause of death, “septic shock”. I understood that he was frail, through the devastating effects of Parkinson’s disease. However, although I am not a clinical infectious disease specialist, to me, this suggests that Ali contracted an infection, almost certainly bacterial, which entered his blood stream. This is what “sepsis” means, and if untreated, a combination of the bacterial growth plus immune responses from the patient can lead to a catastrophic effect called “shock”, which can lead to multiple organ failure and death. In Muhammad Ali’s case, it seems a respiratory infection was the initial problem.

AMRIt is sadly not unusual for frail patients to contract serious infections in hospital. Clinicians are of course ready for this and would have responded by administering powerful antibiotics, hoping to kill the invading bacteria. Unfortunately, increasingly in the modern era, the bacteria causing these infections have become resistant to our better antibiotics. If the antibiotic administered turns out to be ineffective due to resistance, the patient can be rapidly overwhelmed, with fatal consequences.

 

2-how-antibiotic-resistence-happens

by CDC, Centres for Disease Control and Prevention, USA

I have a personal interest in this scenario not only because I have devoted the last 20 years or so to trying to help discover and develop new antibiotics, but also because in 1994 my father died in hospital of multi-organ failure due to sepsis after a routine hip replacement.

2-how_antibiotic_resistance_spreads

by CDC, Centres for Disease Control and Prevention, USA

I don’t know whether Ali’s “septic shock” was due to an antibiotic resistant infection or whether his frail body couldn’t cope with yet another infection. But if antibiotic resistant bacteria were the cause of his death, wouldn’t it be amazing if the publicity and outpouring of grief associated with his passing could trigger a transformational change in our collective resolve to find urgently needed solutions to the impending antibiotic resistance catastrophe. One final positive postscript to his enduring legacy.

 

Links

Antimicrobial review   http://amr-review.org/

Wellcome Trust Antibiotic Awareness Week https://wellcome.ac.uk/news/antibiotic-awareness-week-seven-infections-are-getting-harder-treat

Determination is key – Prof Ramakrishnan’s Baddiley Lecture

By Kevin Waldron.

Last week saw ICaMB host the latest in our series of Baddiley lectures, which commemorates Professor Sir James Baddiley (1918-2008). Baddiley was a distinguished Professor at Newcastle University (1954-81) and a Fellow of the Royal Society (elected 1961) who made numerous important fundamental discoveries in microbiology, not least the discovery of teichoic acids, cell wall components in Gram positive bacteria.

Jeff Errington introduces Venki Ramakrishnan to the ICaMB audience

Jeff Errington introduces Venki Ramakrishnan to the ICaMB audience

Baddiley’s work on the fundamental processes of bacteria, including the structure and function of components of the bacterial cell wall, is continued to this day in Newcastle through the work of members of ICaMB’s Centre for Bacterial Cell Biology (CBCB). Although James Baddiley died shortly after the first in ICaMB’s series of Baddiley lectures, we were delighted that the Baddiley family was again represented at this year’s lecture by James’s son, Christopher Baddiley.

This year’s guest speaker was Professor Sir Venki Ramakrishnan, distinguished research leader and Deputy Director of the Laboratory of Molecular Biology in Cambridge, Nobel laureate and newly-elected President of the Royal Society. With all of the demands on his time that come with this new role as President, the large audience that gathered on Friday afternoon were grateful that Venki was able to find time to visit Newcastle to deliver his lecture. As ever, both the lecture and the surrounding celebration was expertly organised and introduced by CBCB Director, Professor Jeff Errington.

Venki illustrates the structure of the yeast mitochondrial ribosome

Venki illustrates the structure of the yeast mitochondrial ribosome

Venki’s lecture gave a brief history of his atomic-resolution structural studies of the ribosome, the macromolecular nucleoprotein complex that converts the four-letter genetic code in nucleic acid into the twenty-letter amino acid code in proteins. He presented detailed structural models of eukaryotic ribosomes, derived from X-ray crystallography and cryo-electron microscopy data accumulated over 30 years of detailed study in his laboratory.

We asked some of ICaMB’s early career researchers to describe their impression of Venki’s lecture:

“Professor Venki Ramakrishnan was kind enough to deliver this year’s Baddiley lecture. It was an honour to meet Venki, who somehow managed to fit us in between Royal Society committee meetings and a chat with the Science minister! He impressed us all with a phenomenal talk discussing how he solved the structure of the mitochondrial ribosome using cryo electron microscopy. Wow – cryo EM has truly moved beyond blob-ology! One thing that really struck me about Venki is how humble he is; despite being so incredibly successful and lauded, there’s not a trace of ego on the guy; something for us all to aspire to.”

Venki illustrates how the ribosome works

Venki illustrates how the ribosome works

Seamus Holden, University Research Fellow

“It was incredibly cool to hear about Venki’s work first hand. The enormity of his achievement became clear when he showed a single slide with the dozens of conformations of the ribosome’s catalytic cycle and indicated that there were structures available for the majority of them! And what was humbling was that Venki did not seem at all interested in dwelling upon his past successes. Rather, he briskly moved past this slide onto his current work regarding mitochondrial ribosomes which was both cutting-edge but also somewhat raw because of its novelty. I found it inspiring to see a scientist of his stature still so driven to continue discovering and learning.”

Post lecture, Venki holds the gift he received from his hosts at ICaMB

Post lecture, Venki holds the gift he received from his hosts at ICaMB

Heath Murray, Royal Society URF

“For me Venki’s journey was an excellent advert for never giving up. Often as researchers (particularly at the start of our careers) we are encouraged to know when to call time on a set of experiments that are bogged down and not yielding answers. Pursuit of the next grant and the speed of some of our competitors unfortunately make it risky to continue to spend years and years believing in the same project that fails to show progress relatively quickly. Yet what an example Venki is, many years and many postdocs focusing on the same problem, persistence and belief in himself and his team has more than paid off. Inspirational.”

Suzanne Madgwick, Wellcome Trust Career Re-entry Fellow

Happy 60th birthday, Jeff!

by Prof Jeff Errington

Daunting 60?

IMG_4117I turned 60 on the 3rd of May. The year leading up to that was traumatic for me because, psychologically, it felt like a turning point in life – a long and enjoyable career behind me but a rapidly foreshortening window ahead! Surprisingly, things suddenly looked up when the birthday actually arrived (last Tuesday) – I didn’t really feel any different!

Jeff welcomes everyone as an audience of friends and colleagues gathered for celebrations

Jeff welcomes everyone as an audience of friends and colleagues gathered for celebrations

And then I had a really exciting science symposium and lab reunion to look forward to, which took place on Friday (mostly science) and Saturday (mostly fun!).

henrique

So many wanted to come!

davidquote2We wondered how many of the past members of the lab would be able to make it, given that they were scattered to the four corners of the earth and we had no funds to cover their expenses. To my astonishment and delight, over 20 lab alumni agreed to come, and we were able to fill all of the 16 speaker slots with alumni from outside Newcastle.

Alumni came from far and wide to join the celebrations.

Alumni came from far and wide to join the celebrations.

The speakers came from 4 different continents, and though most were high powered talks on bacterial cell biology, other topics extended through yeast and worms to bat wing development!

wilfried

Meriem El Karoui explaining the mathematical model used in her work on DNA repair

Meriem El Karoui explaining the mathematical model
used in her work on DNA repair

nicolaquote

Nicola explains how her group collects bats for their developmental biology research.

Bat collection methods by Nicola

ianA day of great science – and warm friendship

Fun trip down memory lane

Fun trip down memory lane

dennis

I was overwhelmed by the experience: seeing so many old friends again, the fantastic quality and quantity of science, and the showering of gifts and kind words.

IMG_3721

 

jan

"Looking back at the pictures from my time in Newcastle, it seems we were always doing fun stuff together, something really only possible because Jeff is such a great guy!" Jan-Willem

“Looking back at the pictures from my time in Newcastle, it seems we were always doing fun stuff together, something really only possible because Jeff is such a great guy!” Jan-Willem

I was of course obliged to attempt some profound words at the closing. What struck me was that I could not work out what it was that I had done which had resulted in such an amazing scientific legacy.

philippeThe only thing that I can think of is that if you can once assemble a critical mass of good scientists, which includes a few very good people, the culture or ecology of the lab becomes self sustaining. New people coming into the lab are well trained and inspired by the existing members, and they in turn go on to succeed in their own right. My job mainly becomes one of trying to make sure that the environment and infrastructure of the lab is capable of enabling good scientists to achieve their potential.

adele

IMG_5727

heath

We all agreed that it had been a great idea to get everyone back together again and we plan to have another reunion (outside of any special birthday) again in a few years’ time.

Happy birthday, Jeff!

Happy birthday, Jeff!

Congratulations, Prof Gilbert, FRS!

by Prof. Harry Gilbert, FRS, FMedSci

I was asked to write a blog about my election as a Fellow of the Royal Society. I start by apologising for my ineptitude compared to the “professional” social media people in the Institute. So, what to say? Well, maybe the process might be of interest.

How do you get elected as an FRS?

ICaMB's FRS: Prof Jeff Errington and Prof Harry Gilbert

ICaMB’s FRS: Prof Jeff Errington and Prof Harry Gilbert

You need to be proposed and seconded by current FRS’s. Jeff tried twice to propose me before I went to the USA and a third time (September 2012) upon my return, at which point I said OK. I had to generate a full CV, list 20 papers and include PDF versions of these articles, and the proposers were required to write a three page narrative on my research.

 
Every year material is updated. The first year I wondered what feedback I might get but I soon realized that no one says anything to you. I rapidly put the issue to one side and did not give it any thought.

miebio2014570

‘Wrong Direction’ – Prof Gilbert forms a karaoke boyband with other eminent scientists at a conference in Japan

 

Looking back on my research it’s evident that most of my science was done with collaborators who are much smarter than me. So, I consider myself to be extremely fortunate to have worked with these people.

 

 

The talented people currently working in the Gilbert/Bolam labs

The talented people currently working in the Gilbert/Bolam labs

Bernard_quote

Finally, the election

In late March of this year, I received a letter from the Royal Society marked “In strictest confidence“. I assumed it was yet another reference for someone applying for a grant to the Royal Society and I thought “another job to do”. I read the letter several times and the words “you are on the list of candidates submitted to become an FRS” was hard to digest. When it said you needed 2/3 of the votes to be elected, I became dubious about my chances. On speaking to Jeff, he explained that only one person in the last 150 years has failed to become an FRS at this stage. I was thus confident that not even I could screw this up.

Fun celebrations!

Fun celebrations!

However, keeping it secret for a month before the election took place was extremely hard as I don’t do secrets. I did, however, tell Rosie, my wife, who initially shared my excitement of the news. Her enthusiasm waned somewhat as I kept on about it at home for a day or two. At this point, Rosie said “I hope you don’t become too grand” which ceased any talk about the FRS. I am pleased to say that Rosie’s excitement was rekindled when she realised that she will likely get the opportunity to meet Brian Cox (who also became an FRS this year) who she rates as “very dishy, particularly for a scientist”.

 

How does it feel to be an FRS?

What are my thoughts about being an FRS? Well, shocked but also excited, although I feel a complete fraud.

Prof Gilbert's speech to his colleagues at ICaMB

Prof Gilbert’s speech to his colleagues at ICaMB

I was very pleased that so many people were able to come and celebrate with me on Friday, I would like to thank you all for coming. I also hope that people will think that “if Harry can become an FRS then the bar is not so high”, and that this will result in other people becoming Fellows in the next few years. In 30 years at Newcastle, I have never worked in a place with so many talented people, and it is clear that ICaMB merits more than two Fellows of the Royal Society.

bobquote2

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.