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

Posted on 16 February, 2017 by Paula

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

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….

Muhammad Ali, sepsis and antibiotic resistant superbugs

Posted on 9 June, 2016 by Paula

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.

AMR It 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.

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.

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

Congratulations, Prof Gilbert, FRS!

Posted on 5 May, 2016 by Paula

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

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.

‘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

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!

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

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

Spending Review 2015 – what does it mean for science?

Posted on 27 November, 2015 by Paula

by Paula Salgado

After many months of speculation and concern, the details of the Spending Review 2015 when it comes to science feels, at first, as a massive relief. After all, the Chancellor announced that science funding would be protected in real terms this time, “raised to £4.7bn by 2020 and capital spending to remain at 6.9£bn over this period”. We should be celebrating, surely! However, a detailed analysis shows that this really means that public investment in science will be frozen for the next 5 years. In fact, according to a detailed analysis (source: Scienceogram.org):

The Science Budget is and will remain lower in real terms than it was in 2010.
The Science Budget is falling per person living in the UK, and as a fraction of GDP. By 2020, the Science Budget will be nearly 20% lower as a fraction of GDP than it was in 2010.

And we also need to look at the details, not just the main headlines. The science resource budget (those £4.7bn) will now include a newly announced Global Challenges Fund “to ensure UK science takes the lead in addressing the problems faced by developing countries whilst developing our ability to deliver cutting-edge research.” Depending on how this fund will be managed and organised, there is a concern that this could mean that some of the funds which are currently part of the Science Budget will be diverted to sustain the Governments commitment to spend 0.7% of GDP on international development.

It is also still not clear how the implementation of the Nurse Review in to how Science is funded in the UK will undoubtedly affect the funding landscape. Setting up an overarching structure will have its costs and we need to see how that will translate into funding allocation.

But most importantly, this flat cash real-terms freeze is yet another failed opportunity to increase investment in research and development that is required to maintain the UK’s leading role and sustain economic growth. Five years of flat cash has already had a detrimental effect on R&D, not only in terms of the decline in available funds but also in reputation and work of labs across the country. With the positive economic signs announced by the Chancellor, the Government had a chance to reverse the current managed decline of R&D in the UK but decided to continue on a similar path. The long term effects of these decisions will only be clear over the next few decades – but that is why many, including the Wellcome Trust and RCUK, reacted with caution at the real-term freeze announcement.

The lead up to the Spending Review

Lettter in FT calling on the Chancellor not to cut science funding (Sept 7, 2015)

With rumours of 20 to 40% cuts being “leaked” throughout the summer and even a rushed review from a private consulting company looking on how to make cost savings across the Department for Business, Innovation & Skills (BIS), the scientific community had reasons to be concerned. Many voices spoke publicly against the axe falling on public science funding: a letter from many charities and learned societies, together with several companies was published in the Financial Times, UK top scientists sharing their views on Buzzfeed and several opinion pieces in the media from leading scientists and journalists urged the Government to not impose any cuts and seriously consider increasing current investment in order to support future growth. Behind the scenes, influential learned societies and campaign groups lobbied the Chancellor, the new Minister for Universities and Science, Jo Johnson, and the new Secretary for BIS, Sajid Javid to stress the same points. And the House of Commons Science & Technology Committee made detailed recommendations that the science budget should be increased, just a few weeks before the Spending Review announcement.

Science is Vital chair, Dr Jenny Rohhn, and vice-chair, Prof Stephen Curry, at the rally in London, 26th October 2015

But it wasn’t just prominent voices. As in 2010, Science is Vital organised a grass roots campaign to get the voice of scientific community and all supporters of science be heard. There was a big science event in London with scientists, patient groups, journalists and entertainers all rallying to support sustained public investment in science. Across the UK, local events raised the same issues within local communities, getting people to joint watch the event in London but also discuss how science is important to them. And nearly 2000 people wrote a postcard to George Osborne, telling him why they thought Science is Vital.

Science Minister commenting on Science Budget announcement in Spending Review 2015 on Tweeter

The fact that the Science Minister has now used the phrase “Science is Vital” publicly in at least two occasions, including in his reaction to the SR2015 on social media, means that this important message is getting across our politicians and key decision makers. As more details of the Spending Review are announced in the coming days and weeks, we will surely have opportunities to continue to let them know why Science is Vital.

What do you think? You can leave your comments below.
Science is Vital is also asking for your reactions.

When a Teardrop Can Kill: The Deadly Ebola Virus

Posted on 26 March, 2015 by Neil

March 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

As 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.

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!

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.

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

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 immunological 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.

There 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 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

Posted on 12 March, 2015 by Neil

UK 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.

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

My 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.

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)

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.

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.

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.

In 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.

PhD studentships for 2015 – now recruiting!

Posted on 16 February, 2015 by Paula

As final year undergraduate students up and down the country approach the end of their degrees, it’s decision time. For many, postgraduate studies are the chosen route in the topic that has excited them the most during the their undergraduate studies. If you, or a friend/colleague, are one of those that find Cell and Molecular Biosciences the main topic of interest, this post is for you.

A view of Newcastle, taken during ICaMB’s annual boat trip – you could join us next year!

Would you like to do your PhD in one of the top UK Research Institute for Biological Sciences? In a city that has just been voted as the best city in the UK? Then one of the PhD studentships currently available at ICaMB could be what you are looking for!

As an ICaMB PhD student, you will benefit from being in a dynamic and well funded research environment with access to state of the art technology. You would be working amongst leading experts in several fields from bacterial cell biology all the way through to eukaryotic cell signalling and cancer research.

We all know that a PhD is not only about your research, so you will also be part of a thriving community of postgraduate students, with many events, both social, scientific and career oriented, organised by ICaMB’s PhD student association PAN!C. You can read more about PAN!C in a previous ICaMB blogpost.

Here we list MRes/PhD Studentships scheduled to begin in ICaMB in September 2015. These are also listed on the ICaMB website, where you can also find further details and guidelines on how to apply. However, if you would like further details about the projects, you can contact the named supervisor directly or the ICaMB Postgraduate Tutor Dr Tim Cheek (email tim.cheek@ncl.ac.uk). In addition, the Institute expects to kick start the careers of several new academic recruits by offering associated postgraduate studentships in the new academic year, September/October 2015. These posts will be advertised before the end of February 2015. If you are potentially interested or would like more details at this stage, please contact Professor Bob Lightowlers, Director of ICaMB. (Robert.lightowlers@ncl.ac.uk)

Newly added:
Title: Investigating the nanoscale structure and function of the bacterial cell division machinery
Sponsor: Newcastle University
Supervisor(s): Dr Seamus Holden, Prof. Jeff Errington
Contact for further details: Dr Seamus Holden (seamus.holden@epfl.ch)
Interested in combining bacterial cell biology with cutting-edge super-resolution microscopy techniques to figure out how bacteria divide?
The structure and dynamics of the bacterial cell division machinery remain mysterious, because this machinery is spatially organized on the nanometre scale, below the resolution of conventional light microscopy. The studentship will focus on using single molecule super-resolution microscopy to study bacterial cell division in living cells, in order to elucidate the physical mechanisms of cytokinesis. Cross-disciplinary training will be provided in advanced microscopy, biophysics, molecular biology and microbiology.
Deadline: This position will be advertised shortly. In the meantime, please contact Dr Seamus Holden for further information.

Pathogens

Title: MRes/PhD Studentship in the Institute for Cell and Molecular Biosciences – Ebola Virus Vaccine: Development of a Salmonella-Based Vaccine Delivery Platform – Ref CB113
Sponsor: Barbour Foundation
Supervisor(s): Dr Anjam Khan (Newcastle), Dr Pietro Mastroeni (Cambridge University) and Dr Gary Kobinger (Manitoba University, Canada)
Contact for further details: Dr Anjam Khan
Interested in contributing towards the development of a novel Ebola virus vaccine? Ebola is a highly virulent virus causing severe haemorrhagic fever with a high fatality rate in humans. This PhD project will explore the application of Salmonella as a novel oral vaccine delivery system for Ebola. The studentship will involve designing and constructing new vectors to optimize the expression and immunogenicity of recombinant Ebola antigens.
Cross-disciplinary training will be provided in molecular biology, microbiology, biotechnology, infection, and immunity. Training will also be provided in the collaborators laboratories in Cambridge.
Further Information

Title: STFC Funded PhD Studentship in Biophysical Chemistry – Creating realistic models of bacterial outer membranes for antimicrobial research and diagnostic assay development – Ref CB114
Sponsor: Science Technology and Facilities Council (STFC) & OJ-Bio Ltd
Supervisor(s): Prof Jeremy Lakey, Dr L Clifton & Dr V Lawson
Contact for further details: Prof J Lakey
This studentship builds up on recent successes in the Lakey research group developing accurate models of the outer membrane of Gram negative bacteria. These will enable more efficient research in antimicrobials and diagnostics. The successful applicant will demonstrate enthusiasm for this cross disciplinary area of research and any science degree including biochemistry, chemistry, physics etc. is suitable. The project involves a collaboration between Newcastle University, the Rutherford Appleton laboratory and OJ Bio, a young diagnostics company. The student will spend time at the neutron source at the Rutherford Appleton laboratory at Harwell.
Further Information
Deadline: The position will remain available until suitable candidates are appointed. Early application is advised.

Title: Sporulation in the human pathogen Clostridium difficile: structural and functional studies – Ref CB115
Sponsor: Medical Research Council (MRC)
Supervisor(s): Dr Paula Salgado and Prof Waldemar Vollmer
Contact for further details: Dr P Salgado
Are you a keen, motivated student, with an interest in microbiology and/or structural biology and an inquisitive, curious approach to research? Interested in bacterial pathogens, antibiotic resistance and in bacteria causing hospital acquired infections? The student will benefit from exceptional training in diverse disciplines: molecular and cell biology, protein purification, structure determination and PG biology to provide new understanding into Cdiff sporulation that would open new therapeutic avenues.
Further Information
Deadline: The position will remain available until suitable candidates are appointed. Early application is advised.

Eukaryotic cell biology and ageing

Title: The impact of a senescent-like phenotype in post-mitotic cells and its impact on ageing – Ref CB116
Sponsor: Medical Research Council (MRC)
Supervisor(s): Dr J Passos, Prof D Young & Dr N LeBrasseur
Contact for further details: Dr J Passos
This project aims to understand mechanisms of ageing using mice models, particularly the role of telomeres and mitochondria and inflammation in the process. It involves a rotation in the Robert and Arlene Kogod Center on Aging, Mayo Clinic (US).
Further Information
Deadline: 28th February

Title: Role of mitochondrial Reactive Oxygen Species in Parkinson’s disease – Ref CB117
Sponsor: Medical Research Council (MRC)
Supervisor(s): Dr A Sanz, Dr A Reeve, Dr V Korolchuk & Prof D Turnbull
Contact for further details: Dr Alberto Sanz
The project aims to better understand the causes of Parkinson’s disease creating new Drosophila melanogaster models and using mammalian cell cultures.

Further Information
Deadline: The positions will remain available until suitable candidates are appointed. Early application is advised.

One new aspect of the PhD studentships on offers this year is a renewed partnership with the Universities of Durham and Liverpool, with which we have a joint BBSRC Doctoral Training Partnership. This is a strategic partnership in Biosciences doctoral training between three research-intensive universities in these three northern cities of great industrial heritage.

The Partnership is offering up to 16 four-year fully funded studentships starting in October 2015. A wide range of 28 projects across the Partnership are available for application under the broad themes of Agriculture & Food Security, Bioscience for Health and World Class Bioscience.

As the leading institute in Newcastle carrying out BBSRC-funded research, many of the projects on offer in Newcastle will be based in ICaMB. Please note that these research projects are in competition for funding with one another. There are two stages to the selection process and usually the projects which receive the best applicants will be awarded the funding.

Projects available at ICaMB, deadline 28th February

Title: Investigating the essential role of copper in biotechnologically important bacteria
Sponsor: BBSRC DTP
Supervisor(s): Prof C Dennison, Prof J C Murrell & Dr K Waldron
Contact for further details: Prof C Dennison
Further Information

Title: Communication across the membrane during bacterial cell division
Sponsor: BBSRC DTP
Supervisor(s): Prof R Lewis & Prof W Vollmer
Contact for further details: Prof R Lewis
Further Information

Title: Role of telomere-driven senescence in age-dependent muscle decline
Sponsor: BBSRC DTP
Supervisor(s): Dr J Passos, Dr Aphrodite Vasilaki & Dr Nathan LeBrasseur
Contact for further details: Dr J Passos
Further Information

Title: Interventions that affect fitness of cells and animals with dysfunctional telomeres
Sponsor: BBSRC DTP
Supervisor(s): Prof D Lydall, Dr N Kenneth, Prof A Morgan & Prof C Price
Contact for further details: Prof D Lydall
Further Information

Title: Fungal-specific RNA endonucleases: novel targets for anti-fungal agents
Sponsor: BBSRC DTP
Supervisor(s): Dr C Schneider, Prof M Caddick & Prof J Quinn
Contact for further details: Dr C Schneider
Further Information

Title: The impact of novel chromatin regulators on genome stability
Sponsor: BBSRC DTP
Supervisor(s): Dr L Maringele & Dr S Grellscheid
Contact for further details: Dr L Maringele
Further Information

Title: The identification of key virulence factors involved in the host-bacterial interaction of Salmonella typhimurium ST313
Sponsor: BBSRC DTP
Supervisor(s): Dr P Aldridge & Prof J Hinton
Contact for further details: Prof P Aldridge
Further Information

Title: Virulence factors of human and bird Trichomonad parasites targeting host proteoglycans: integrating evolutionary biology, comparative genomics, biochemistry and cell biology
Sponsor: BBSRC DTP
Supervisor(s): Prof R Hirt, Dr D Bolam & Prof N Hall
Contact for further details: Prof R Hirt
Further Information

Title: Re-engineering the metabolism of the bacterium Bacillus subtilis for the synthesis Mycosporine-like amino acids
Sponsor: BBSRC DTP
Supervisor(s): Professor C Harwood (Newcastle), Dr Malcolm Horsburgh (Liverpool), Dr Douglas Cossar (Croda Europe)
Contact for further details: Professor C Harwood
Further Information

Title: Ammonium sensing in the wheat pathogen Zymoseptoria tritici
Sponsor: BBSRC DTP
Supervisor(s): Dr J Rutherford, Prof B van den Berg and Dr A Sadanandom
Contact for further details: Dr J Rutherford
Further Information

Donating hope – a success for parents in danger of transmitting mitochondrial disease

Posted on 5 February, 2015 by Paula

by Prof Bob Lightowlers

It was 2pm on a Tuesday afternoon and there I was watching television in my office. An unusual experience (honestly) but it was to be a truly momentous occasion. For the next 90 minutes, members of parliament would be debating whether to sanction the procedure of mitochondrial donation. What on earth does that mean ? Well, mitochondria are essential compartments (or organelles) that provide numerous key functions for the cell. They also have their own genome, called mitochondrial DNA – mtDNA – that contains the information to make up just 13 proteins, all of which are important in their function of producing main energy source of the cell, ATP. This is why mitochondria are often referred to as the cell’s batteries or the powerhouse of the cell. It is important to note that mtDNA is very small when compared to the nuclear DNA component: 16 thousand mitochondrial nucleotides (that is, the “letters” in the genetic code) vs more than 3 billion nucleotides in the nuclear DNA.

OK, but why would you want to donate mitochondria?

Mitochondrial DNA is strictly passed down via our mothers, unlike nuclear DNA which is comes from our father and mother. Almost 2,500 women in the UK have mutations in some or all of their mtDNA that can cause disease. Defects of this mitochondrial genome, can be responsible for a wide spectrum of mainly muscle and neurodegenerative disorders for which there is no treatment. By identifying those women with defective mtDNA, we could potentially prevent transmission of their unhealthy DNA by substituting their mitochondria for organelles from a donor. Simple on paper!

What’s the problem?

There are two major barriers. First, how safe would any technique be for mitochondrial donation ?

The pronuclear transfer method: Embryos are shown with mitochondria carrying normal (green) or mutant (red) mtDNA.
As the embryos begin to develop, pronuclei become visible. Pronuclei from the normal donor embryo are removed (blue, top panel ‘enucleation’) and are replaced with the nuclear DNA from the patients (red, karyoplast). The resultant embryo carries nuclear DNA from the patients and mtDNA from the donor (mitochondrial donor zygote).

The technique being championed in Newcastle is that of pronuclear transfer. The idea is to take the nuclear DNA from a fertilised embryo and transfer the DNA to a donor with no nuclear DNA, ie, where the nucleus was removed. The newly made embryo then has nuclear DNA from the mother and father but has only mtDNA from the donor.
As you can tell, there is quite a lot of tricky manipulation here. Further, although the mtDNA that has been replaced carries only a very small number of genes, could these somehow be incompatible with the nuclear DNA?
After many years of very careful analysis, there is no evidence to suggest that this procedure is unsafe. The question of incompatibility would also seem to be highly unlikely. After all, nature has been performing the experiment of mixing and matching nuclear and mtDNA since the evolution of Homo sapiens. The idea that, for example, there would be something wrong with the child of an aboriginal woman and a inuit man due to the substantial differences in their mitochondrial DNA would seem laughable.

In addition, does the replacement of DNA, albeit the complete mitochondrial genome, constitute genetic manipulation? This is a contentious issue and a strict definition of what constitutes genetic manipulation, particularly when concerning mtDNA, is difficult to agree on. It must be remembered that mtDNA is completely separate from nuclear DNA and needs to be considered as such.

A separate issue is that many people are ethically uncomfortable with this process. Can embryo manipulation ever be acceptable? Certainly, many religious people have a deeply felt objection to this.
Even when we accept that these methods could offer such an immeasurable benefit for many couples, it is clear that there were many questions to be tackled before we could consider the prospect of mitochondrial donation. For this reason, experimentation and public consultations had to be initiated.

The Parliamentary Under-Secretary of State for Health, Jane Ellison, when presenting the vote on Tuesday highlighted the measures taken to date to assess the safety and ethical concerns surrounding mitochondrial donation.

To cut a very long story short, both have been carried out for many years, including supportive public consultations and independent review by the Human Fertilisation and Embryology Authority (HFEA) reporting that the procedure was not dangerous, as we’ve covered before (here and here). Following these procedures, Professors Turnbull, Herbert and numerous members of the Wellcome Trust Centre for Mitochondrial Research were instrumental in persuading the government to finally hold a debate in the House of Commons.

The vote scheduled for Tuesday afternoon would decide whether the HFEA would have the right to offer a licence to perform mitochondrial donation, a first for the UK and the world. The week leading up to the debate was a white-knuckle ride. Letters of support were published in leading newspapers from Nobel Laureates and other eminent scientists. Just when it appeared that the tide was turning, the Church of England announced it could not support mitochondrial donation. This was a great disappointment and rather a shock, as they had been involved throughout the lengthy consultation processes and had not indicated their level of concern.

Now a back-benh MP, former Minister for Science, David Willets, made a clear case in support of mitochondrial donation.

Now a back-bench MP, former Minister for Science, David Willetts, made a clear case in support of mitochondrial donation. You can read the whole debate here.

Back to me watching the television. At 3:45pm, the members had cast their votes and the count was in – 382 for the motion, 128 against! This is a fantastic result. It gives couples who may be at risk of having a baby with mitochondrial disease the chance to choose whether they want to try mitochondrial donation, just like couples have been able to choose in vitro fertilisation since the 1970’s.

Obviously, this result has gathered lots of media interest and even I was rolled out to perform a couple of interviews.

There is still more to be done, however. Further important research to support the safety of the procedure is currently in review but it must be recognised that every clinical procedure carries a risk. What this vote does is to empower the HFEA to licence this procedure in the UK, but this is still an important barrier and many issues are still to be addressed. And it also needs to be discussed by the House of Lords, of course.

Regardless, today’s vote was a wonderful day for anyone who has been touched by mitochondrial disease in any form. Twenty years ago, Doug Turnbull and I used to discuss this idea. He and his colleagues have done a remarkable job to make this pipedream a reality.

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

Posted on 18 December, 2014 by Neil

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 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……

……. 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

A CBCB Cell-ebration

Posted on 24 July, 2014 by Kevin

Earlier this month, the Centre for Bacterial Cell Biology held its inaugural Symposium. Here, the CBCB’s Heath Murray and Kevin Waldron tell us about what happened at the event.

One of the aspects of ICaMB that makes it a unique institute is the Centre for Bacterial Cell Biology (CBCB), a group of researchers who are focused on understanding fundamental biological questions using bacteria as model organisms. The CBCB was founded by Professor Jeff Errington FRS and is the world’s first major research centre with a focus on bacterial cell biology. Since its inception, CBCB has relocated to a purpose-built £30 million facility in the Baddiley-Clark Building, and has grown to include more than 20 different research groups. In a relatively short time, CBCB members have made outstanding contributions to our understanding of numerous aspects of fundamental cellular processes in a wide range of bacteria.

Prof Kenn Gerdes from the CBCB discusses how bacteria can form dormant variants that evade the immune defence response.

In order to recognise the success and the breadth of science being generated in the Centre, we recently held the inaugural CBCB Symposium on July 9-10. More than 120 members of the CBCB community participated in the two-day event, underscoring the critical mass of researchers at Newcastle University working within the field. This excellent turnout certainly contributed to the overall success of the event.

Research themes covered by talks from group leaders in the CBCB included sporulation, infection, persistence, biofilms, metabolism, motility, and morphogenesis. We also heard about the emerging subject of synthetic biology, where bacterial organisms will be programmed much like computers to perform discrete biological tasks.The CBCB Symposium was highlighted by inspirational talks from three distinguished external scientists, Jan Löwe (Laboratory of Molecular Biology, Cambridge), Mervyn Bibb (John Innes Centre, Norwich), and Simon Foster (Department of Molecular Biology and Biotechnology, Sheffield).

Prof Simon Foster explains how the superbug Staphylococcus aureus grows and divides.

Professor Löwe discussed his work using a range of biochemical and structural approaches to analyse the bacterial cell division and morphogenesis machinery. Professor Bibb explained how his lab utilises a combination of next generation DNA sequencing and bioinformatics with classical genetic analysis to discover novel antibiotics. Professor Foster showed how studies on the fundamental aspects of bacterial cell biology can be harnessed to better understand host-pathogen interactions that can eventually be translated into vaccine development, with his focus on the ‘super bug’ Staphylococcus aureus..

Participants hold discussions over dinner and drinks following the Symposium.

At the end of the Symposium participants gathered together for dinner and drinks in the informal setting of the Forum. This provided an interactive end to the event that allowed researchers throughout the CBCB to meet one another, discuss the amazing science, and develop connections.

ICaMB – Inside Cells and Molecules Blog

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