The gender agenda: ICaMB welcomes the Athena Swan debate.

Posted on 21 May, 2015 by Kevin

If you work in academia, then undoubtedly you will have heard something about the Athena SWAN charter over the last year or so. Athena SWAN is a national scheme that aims to rebalance the gender ratio in higher education and research, with a particular focus on employment in the STEMM (science, technology, engineering, maths and medicine) subjects. Like other research institutes, ICaMB has been engaged in this initiative, and were delighted to receive a bronze award when the results were recently announced.

However, Athena SWAN is not without its controversies. Although most (if not all) academics agree that the gender imbalance is a problem, not everybody agrees on the causes or on the best way to fix it. New research is published on the gender gap every week, but even this can prove contradictory (see for example here, here, here and here).

Today, we get two different personal opinions on Athena SWAN from members of the ICaMB Athena SWAN Self-Assessment Team. First, we hear from Suzanne Madgwick, who says she doesn’t feel she has experienced the kind of discrimination that is often posited as a major cause of academic gender inequality.

Next we get the view of Nancy Rios, who tells us more about the gender imbalance, the Athena SWAN charter, how ICaMB has responded to it and what kind of changes can be put in place to make a positive impact.

On the ICaMBlog team, we are aware that this issue is not without controversy. However, we believe that the best way forward, as we proceed towards applying for silver and ultimately gold Athena SWAN status, is to have an open debate about these issues. We’d like to hear your opinions on this subject and are keen to hear from anyone who would also like to write an article on this subject. Please leave a comment below and join the conversation.

Not Athena SWAN again! The Good, the Bad and the Ugly

Posted on 21 May, 2015 by Suzanne

In one of today’s dual posts, we get the personal opinion of Suzanne Madgwick, a research fellow in ICaMB, about her experiences and the pros and cons of Athena SWAN.

The following opinions are all my own and not necessarily those of ICaMB, other good opinions are available; no men or women were harmed during the preparation of this article.

4^th of November 2013 was the first time I heard the term Athena SWAN. An email dropped into academic inboxes, a message which has no doubt been rolled out in one form or another across countless institutions throughout the country. Something along the lines of: ‘Inequalities between male and female academics which may exist need to be addressed ….. For many granting bodies this is becoming a major issue …….. NIHR have made it very clear that only institutions with at least an Athena Swan Silver Award will be eligible ……… others may follow …….. Self-Assessment Team …….. Application ……Volunteers’

Three thoughts ran through my head

Primarily confusion, in this position I can’t think of a time when I have felt discriminated against. Where has the notion that gender inequality exists in ICaMB come from? Whether I succeed or fail is based on many things; academic ability, resilience, character, free personal life choices and of course luck among others. I cannot currently identify a factor that could be singled out as a gender barrier. Sure, we work in a traditionally male-dominated environment but this is changing, gradually yes, but as far as I can see without conflict or resistance. Might it then be damaging to try and force this?

Secondly, why is there a possibility that government and charity money may in future only be awarded to institutions with a specific award? Is this necessarily the most responsible spend of money? When did the best research team stop being the one with the best idea? Given that there is increasing evidence to suggest that the most productive teams exist within flexible, progressive environments with good levels of female and male representation, again, are we not moving towards this anyway?

My final thought at the time was ‘Uh oh, I’m bound to be ‘asked’ to volunteer for our self-assessment team, this will be awkward’. But I reasoned that whilst I failed to see the existence of a problem I should help the department in an application. The Athena SWAN charter has us backed into a corner and whether I agree with it or not, in some way we will all benefit from an award.

17 months on, I am now trapped in the frustrations of a Jekyll and Hyde type situation. I cannot ignore the fact that I still have these same objections and many more to boot. But I am also pleased to have become increasingly aware of the immense good that can come from a team striving to make improvements in relation to points 2 and 3 covered by the Athena SWAN charter.

The Good; in particular, but not limited to; mentoring schemes for both personal development and career progression, events for early career researchers to help identify and inform funding opportunities, promotion of flexible working hours, technical support and relief from additional duties for staff returning from leave, the formation of a team to identify, sponsor and encourage people who are able and talented but perhaps lack the self-promotion needed to reach the next level ……. and so on and so on. Brilliant! Everybody who has the ability and would like to, has an equal opportunity to stay in science. Creating a more flexible, inspirational working environment for all seems like a great idea, but continually lumping this together with ‘women’s issues’ is putting off a significant proportion of our workforce.

The Bad; nothing listed here is simply a gender issue, they are team issues and I am frustrated that all of these great positive changes are eclipsed by a much more visible yet awkward approach to addressing point 1.

Yes, there is evidence to suggest that women are sometimes a little more risk averse, less likely to put themselves forward for promotion, but this is by no means exclusive. If we have a mechanism in place to champion and support the different needs of all people, each and every time they need it, is this not equality without the need to keep using the word “women”? I can’t help thinking that there is a good dose of hypocrisy in all the ‘positive actions’ and events which are seen to be just for women. In the short term it’s generating friction and in the long term it certainly doesn’t seem like the best strategy when preaching fair play.

Athena SWAN is suffering an image crisis. To the people who are not engaging in the initiative, I can’t blame you. I’m uncomfortable with the image of Athena SWAN and I would assume I’m supposed to be a benefactor. Despite all the good, we are alienating people; they assume it’s not for them, or like me, they don’t see the barrier. Can we consider for a moment that when we’re feeling energised and determined in our careers that it might be a little insulting to tell us we are being discriminated against and may need extra help? Prior to Athena SWAN I felt that my position was born of the factors that I have listed at the beginning of this article. Only now do I look around and wonder.

I’m beginning to get the feeling I have an ‘Athena SWAN’ label. I don’t want to highlight anybody in particular but I am not alone here. It doesn’t take much of an internet search to find high profile women making comments about feeling that recently they’ve been asked to speak more and more about women’s issues and less and less about science.

Of course women are different, 80% of us will have children and not even the power of Athena SWAN can switch over the uterus. But my children are my children, my choice, not a dent in my or my husband’s career. I have taken several years off; I am several years behind a peer who has not taken time out and this is as it should be. But, also as it should be, there were options available to me to return to science. I’m very pleased to report how well supported I have been in this, as I’m sure are the cohort of men who have also gained Career Re-Entry Fellowships.

The Ugly; the corridor murmuring. I’m not going to participate in anything to do with Athena SWAN but I’m going to moan about it anyway. But perhaps people feel they can’t speak up, the ugly side of political correctness. Please challenge us, we may agree with you. I am reminded of Hilary Lappin-Scott’s final phrase at last year’s equality in academia event “best use of all our talent”. Our self-assessment team is not balanced. We are getting lots of things right but we are also getting some things wrong, these are then the points that go noticed. We have certainly tried to concentrate on charter points two and three, but I for one feel very uncomfortable about the fact that we are hamstrung by the need to address all three.

The Leaky Pipeline; we can’t deny the ‘leaky pipeline,’ the drop off in the proportion of female scientists who progress from Postdoc to PI (though current ICaMB fellows are 47% female); the Athena SWAN initiative began with a need to address this. Nevertheless, we also can’t assume that we know all the reasons for the leak. Identifying these reasons is a big part of the challenge faced by the Athena SWAN self-assessment team. As crazy as it might sound, we do not all want to stay in science (though Bob if you are reading, I do). I have recently read that 88% of female PhD students do not want to stay in academia, but then neither do 79% of male PhD students. Surely through sponsorship, mentoring, flexible working etc., we can make sure that everybody who would like to stay in science has an equal opportunity based on merit, without making this an alienating gender issue.

This brings me back to our Athena Swan event last month where Professor Helen Arthur, Jill Golightly and Professor Melanie Welham all gave highly entertaining, outstanding talks about three very different very successful career paths. Sitting in my chair at the end of the afternoon I felt thoroughly inspired not because they are three inspirational women but because they are 3 inspirational people……. Only to then stand up and feel disheartened as turned and noticed the proportion of men in the audience. Have we done this? Has the Image of Athena SWAN has done this? With this in mind ……

Athena SWAN – deconstructed

Posted on 21 May, 2015 by Neil

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

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

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

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

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

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

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

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

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

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

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

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

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

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

So what can Athena SWAN do?

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

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

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

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

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

Links

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

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

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

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

Soapbox Science: http://soapboxscience.org/

When a Teardrop Can Kill: The Deadly Ebola Virus

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.

Happy Birthday PAN!C

Posted on 5 March, 2015 by Kevin

By Beth Lawry

ICaMB’s postgraduate student association (PAN!C) celebrated it’s 2^nd birthday in February. Thank you to all 40+ of the ICaMB postgraduate students who came and enjoyed our night of celebrations!

Yep, if you’re an ICaMB postgraduate student, I’m the one who clogs up your inbox with emails about yet another PAN!C activity. The past few years, since Claire Whitworth and Kerrie Brusby began the ICaMB postgraduate association, have been an amazing whirlwind. To celebrate PAN!C’s birthday I thought I’d share my highlights with you.

PAN!C CV Workshop, June 2014

In February 2013, PAN!C applied for and won a University Innovation Grant, and were invited to celebrate with the Vice Chancellor. These funds have enabled PAN!C to host numerous events, both academic and social, for ICaMB’s PhD student community. In November 2013 we hosted our careers symposium. Of course, we’ve all been given the usual, generic career options for people with PhDs, but that wasn’t enough for PAN!C. We wanted our students to have the opportunity to hear about careers they perhaps had not thought of, and provide the chance to meet professionals in these areas…. We even had an interesting insight into running a pole dancing business! In 2014, PAN!C hosted a CV workshop, with experts providing information on how to improve and tailor your CV to a variety of sectors. We had 12 speakers, and over 60 students attended the day.

PAN!C Climbing, February 2014

Both the Careers Symposium and CV workshop received extremely positive feedback, from students and speakers alike, with 100% of responders stating they’d recommend the workshops. It’s worth noting that, while organising these events, I made contacts with people from industry, teaching, law, business and recruitment, all of whom I’m still in touch with. PAN!C has provided me with a fantastic opportunity to network with my peers, and gain skills in team work, grant applications, leadership and communication.

PAN!C are crowned FMS quiz champions, May 2014

On the social side, PAN!C has always strived to bring together the many groups within ICaMB. Together we’ve conquered our fears and climbed to dizzying heights at the Newcastle Climbing Centre, skated on ice at the Centre for Life in a somewhat Bambi fashion, hit a pin or 2 whilst bowling at MFA Bowl and became Quiz Champions of FMS!

Another highlight was the PAN!C Bake Off, where I almost fell into a sugar induced coma!….. mmmmm cake. And along the way we raised a massive £361.56 for charity (which was split between Macmillan, Doctors without Borders and Age UK).

Fabulous cakes at the PAN!C Bake Off, September 2014

Since forming, the PAN!C committee has had 10 members, and I’d personally like to thank every one of them for contributing and making this association such a fantastic and fun thing to be a part of. I’d also like to thank the ICaMB postgraduate students too. We’re a student led committee for the students and without you we’re nothing!

I’m nearing the end of my stint at Newcastle University, so it’s time to pass the PAN!C reigns over. It’s something that has improved my time management and helped me to focus on my PhD work. I hope you too realise the opportunity that PAN!C offers. You can give as little or as much time as you like, involve yourself with conference organising or just attend the socials. So, get involved and let’s keep the party going!

If you want any further information or just to chat about PAN!C, please don’t hesitate to contact me: b.m.lawry@ncl.ac.uk.

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.

When Tom Williams went to Sci Foo Camp

Posted on 15 January, 2015 by Neil

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

By Tom Williams

Dr Tom WIlliams

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

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

Creation of a Sci Foo conference programme

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

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

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

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

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

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

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

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

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

Links

http://en.wikipedia.org/wiki/Unconference

http://www.digital-science.com/sciencefoo/

http://psp.sagepub.com/content/23/4/363.short

http://www.datadryad.com

http://figshare.com/authors/Tom_Williams/515556

http://www.digital-science.com/people/chris-george

http://acarol.woz.org/

http://www.computerhistory.org/babbage/

http://en.wikipedia.org/wiki/Antikythera_mechanism

http://www.nanoflight.info/

Beer, Bread and Bacteria

Posted on 8 January, 2015 by Kevin

Prof. Harry Gilbert

The diverse organisms that live in our gut, collectively termed the gut microbiota, can have a major impact on our health. A new paper from Prof. Harry Gilbert’s lab in ICaMB, published today in Nature, shows that one member of our gut microflora uses a ’selfish’ mechanism to degrade a component of the cell wall of the yeast in our diet.

By Drs. Elisabeth Lowe and Fiona Cuskin.

Have you over-indulged this Christmas? One too many ales, or too many turkey sandwiches?

Beer: full of yeast.

The good news is that, while your waist line may be expanding and you may be feeling a little the worse for wear, the organisms of your gut microbiota are thriving!

Some of the bacteria in the human gut, called Bacteroides, can break down the complex carbohydrates in our diet into simple sugars, which they use for energy.

: Bread: full of yeast

Our work, published in Nature today, shows that one of these bacteria can also break down some of the carbohydrate cell wall of yeasts, called mannan, a polymer of mannose. This includes mannan from Saccharomyces cerevisiae (Baker’s yeast), and the pathogenic gut fungus, Candida albicans. The current understanding of polysaccharide digestion by gut bacteria suggests a cooperative environment, in which break-down products are shared between different members of the microbiota. However our data shows that this species (Bacteroides thetaiotaomicron) is ‘selfish’ when it degrades mannan, and doesn’t share any of the digestion products with other bacteria.

Turkey: er… full of yeast?

To achieve this selfish degradation, the large and multiply-branched mannan structure undergoes only very limited degradation in the extracellular space (see figure). The resulting processed mannan fragments are then imported into the Bacteroides periplasmic space, where they are further degraded by a suite of glycoside hydrolase enzymes to yield the sugar mannose. Achieving complete breakdown within the periplasm prevents the mannose from being shared with competing bacteria.

This selfish approach to mannan utilisation could offer the opportunity to design bespoke prebiotics targeted to a specific bacterial population within the gut. Food products containing yeast mannan would be expected to promote growth of B. thetaiotamicron, whereas other complex polysaccharides may specifically promote other members of the microbiota.

Complex polysaccharide mannan is sequentially degraded by a ‘selfish’ mechanism to yield periplasmic mannose.

A number of inflammatory bowel diseases such as Crohn’s disease are associated with intolerance to yeast, and particularly cell wall polysaccharides, and have also been linked to low levels of Bacteroides species in the gut. Our work provides a potential mechanism for how Bacteroides might be able to influence the effect of yeast on patients with Crohn’s disease, and in fact a drug named Thetanix (which is a live formulation of Bacteroides thetaiotaomicron) has been licensed for treatment of paediatric Crohn’s disease in the USA.

Researchers Max Temple, Lis Lowe and Fiona Cuskin of the Gilbert lab.

Yeast is commonly in our diet in the form of some of our favourite things: bread, beer, wine and fermented food products. So it may be dry January but if your willpower fails and you succumb to an alcoholic beverage, then make sure it’s an unfiltered one with plenty of yeast!

This research in the Gilbert lab was funded by the Wellcome Trust and the European Research Council.

Links:

Nature article: http://www.nature.com/nature/journal/v517/n7533/full/nature13995.html

Press release: http://www.ncl.ac.uk/press.office/press.release/item/beer-and-bread-yeast-eating-bacteria-aid-human-health

Gilbert Lab: http://www.ncl.ac.uk/camb/staff/profile/harry.gilbert