Skinny Seaweed

Matt

Obesity has reached epidemic proportions globally, with at least 2.8 million people dying each year as a result of being overweight or obese (WHO). Dr Matthew Wilcox from Professor Jeff Pearson’s lab tells us about his research into the slimming powers of brown seaweed. A simple and sustainable food additive. 

“Seaweed bread” by Dr Matt Wilcox

Seaweed bread

Seaweed bread

Over 40% of the calories in your diet can come from fat (mainly triacylglycerol) and you digest and absorb between 95 and 100% of all the fat that you eat!  There is one enzyme (pancreatic lipase) that accounts for 80% of all fat digestion and if the activity of this enzyme can be reduced then we will absorb less fat from our diet.

The Pearson lab has shown that alginate (a dietary fibre extracted from brown seaweed) can reduce the activity of pancreatic lipase by up to 80%.  If you don’t digest fat you can’t absorb it.

Times pictureLipase is a recognised target as a treatment for obesity. In 2010 the pharmaceutical drug orlistat (Xenical) which acts on this enzyme accounted for 98% of all UK prescriptions for the treatment of obesity. The remaining 2% was for Sibutramine which has since been withdrawn. We are therefore heavily reliant upon one drug which can have some rather unpleasant side effects (brown trouser syndrome) greatly reducing patient compliance. So even though it’s the only pharmaceutical drug available, not everyone who is prescribed it will actually take it!

Tasteless alginate is already found in a number of foods (E400-405), salad dressings, ice-creams ..... even beer.

Tasteless alginate is already found in a number of foods (E400-405), salad dressings, ice-creams ….. even beer.

Thankfully there is still hope (and clean trousers) since some, if not all of the side effects of orlistat can be eliminated if it is taken with a high fibre product. Luckily, it just so happens that alginate is not only a lipase inhibitor but is also a dietary fibre itself, and to top it all off makes great bread!

Most commercial alginates come from seaweed, hence the seaweed bread.  The extraction process is relatively simple and you end up with a dry white (ish) powder, great to use in products with flour. There is no ‘seaweed’ taste (although seaweed bread is actually quite nice) and in blinded tests people actually prefer the alginate bread over standard white bread.  Likely to be due to the retention of moisture so it’s like eating fresh bread, even if it’s a day or so old

Seaweed culture and harvesting is big business around the world from the Shetlands to Shanghai and can even be seen from space. The extracted alginates are already used in the food industry, just not necessarily the right ones or in the right concentrations. The majority we test in the lab are from Norwegian or Scottish seaweeds.

The  latest technology in seaweed harvesting.

The latest technology in seaweed harvesting.

The alginate project in the lab started nearly eight years ago with simple colourimetric assays. These initial experiments showed that certain seaweed alginates can inhibit lipase. From this we developed a model of the upper gastrointestinal tract to test the alginates in a system as close to a human as possible without being human. Our model gut has now been used to show that alginate is released from the bread (amongst other things) and has also featured in a BBC3 program. We have just finished the first proof of concept trial in humans, so there will be more on this story to follow.

The Pearson Lab line-up

The Pearson Lab line-up

The big fat truth is that fat in food is often vital for the enjoyment, try eating cream crackers without butter (3 cracker challenge).  It’s hard!  So, if we can still get the enjoyment but not all the calories from our food then we can significantly reduce the amount of calories we take in.  It’s not just a reduction in the absorption of fat in the food that contains the alginate; it’s the entire meal that you eat.  Not that you should eat loads of burgers but if we could put alginate into burger buns then you would reduce the amount of fat absorbed from the burger, the cheese, the fries and the ridiculously oversized milkshake that you have with it.

Low fat lunch?

Low fat lunch?

Perhaps that’s the best way to end a blog with the thought of a ridiculously oversized milkshake and also by thanking the BBSRC for all their funding and support!

Matt’s PhD was a BBSRC CASE studentship sponsored by Technostics

This work has been patented

Full Links

The patent: http://worldwide.espacenet.com/publicationDetails/biblio?DB=worldwide.espacenet.com&II=1&ND=3&adjacent=true&locale=en_EP&FT=D&date=20121129&CC=US&NR=2012302521A1&KC=A1

Technostics: http://www.technostics.com/

Matthew Wilcox: http://www.ncl.ac.uk/camb/staff/profile/matthew.wilcox

Jeff Pearson: http://www.ncl.ac.uk/camb/staff/profile/jeffrey.pearson

One year of the ICaMBlog in numbers

By Neil Perkins

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

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

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

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

So how popular are we?

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

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

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

Someone from San Francisco just started reading the blog

What are people reading?

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

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

Are they really reading these articles?

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

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

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

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

The impact of social media

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

The reddit event

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

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

Any Conclusions?

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

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

IPA Update: The Mysterious World of Biotech

By the IPA committee

On Thursday 30th January for the 4th Science Lives Seminar the ICaMB Postdoc Association (IPA) decided to delve into what it is really like to work in the Biotech industry, by hosting Dr Keith Foster from Syntaxin Ltd (Oxford, UK). For many of us Postdocs, the Biotech Industry is an unexplored entity…so how and why did Keith Foster make the transition from Postdoc to a Biotech company co-founder? And, what advice would he give Postdocs thinking of making the same leap?

Dr Keith Foster giving his presentation

Dr Foster’s talk started by illustrating his personal experience; he obtained a PhD in biological sciences in London then set his sights on a getting a post-doc position. He explained that he had first thought he would head to the bright lights of the USA for this but as his wife’s dentistry qualifications were not recognised over there, the couple moved to Nottingham to pursue their respective careers.  At this point Keith really wanted to pursue a long and successful academic career and said he couldn’t imagine leaving academia.

However, he soon realised that you can never have a career plan set-in-stone as within the first couple of years of his post-doc, Keith and his wife found out they were expecting their first child. He recalled this period as a wake-up call, like an alarm telling him he should get what he considered a “real job”, meaning he wanted a stable, and hopefully permanent job to support his growing family. He said he quickly realised that in a field as dynamic as science you not only have to evolve and make career moves for personal circumstances, but also, because the world of science is ever changing, we never know what to expect around the next corner!

So, from Nottingham, Keith made his big move to industry as a Senior Scientist, the company being SmithKline (before it became GSK). Much to his surprise in his new job, he found that he could still put to use his “passion for science” at the bench and really got a thrill from the drug development and translational aspects of the projects that were new to him. Early on Keith started working on the protein, Botulinum neurotoxin, which he says he  “fell in love” with and this protein remains his passion to this day with Keith recently having opened his own company based on it 20 years or so later, Syntaxin Ltd.

Like many of our PIs, being the big boss at Syntaxin Ltd means that Keith does not himself spend time at the bench, but he does insist that any Postdoc going into a company as a Senior Scientist would have to do lots of bench work, making what an academic postdoc and an industrial senior scientist do on a daily basis “very similar”. We should however expect a pay rise! Nice!

Keith Foster’s company was recently bought by a French company (IPSEN). This is where one of his biggest pieces of advice came from… always leave on good terms, and try not to make any enemies! It turns out that IPSEN actually made Keith redundant earlier on in his industrial career. However, Keith moved on, working at a handful of other companies on his way, but couldn’t believe it when he managed to shake hands with IPSEN over a multi-million dollar deal for his company all those years later! A real lesson in the importance of networking and maintaining those contacts!

Another point that Keith highlighted was that Biotech or the pharmaceutical industry may not be the holy grail that many PhD students or post-docs think it is…. he posed the question is there really more job stability there these days? In academia we have fixed two or three year contracts, but industry is also highly competitive and money is hard to come by, with some firms choosing to move away from the UK and making redundancies.

To wrap this seminar up, like all our Science Lives Seminar speakers, we asked him to mention how he managed to handle a personal life and successful research career in parallel. Being a father of 4, and now a grandfather of 5, he obviously didn’t spend all of his time working. He did say however “my wife laughed when she read this question”. They obviously would not have both given the same answer!

After the seminar there was the usual informal session for post-docs to ask questions over a glass of wine or a beer, and after the IPA committee enjoyed a friendly and filling meal with Keith at the Broad Chare.

The IPA is in the process of organising our next social event, updates will follow by email and on the website. Look out!  If you would like to become involved with the IPA and help organise future events, please get in touch!

IPA Committee

IPA is run by Postdocs, for Postdocs. Get involved!


IPA page on the ICAMB website: http://www.ncl.ac.uk/camb/research/postdoc/association/

IPA Facebook page: https://www.facebook.com/groups/462376430446559

Institute for Cellular and Molecular Biosciences: http://www.ncl.ac.uk/camb/

Students take the stand: 2nd Year Post-Graduate Research Talks Day

 

by Dr Tim Cheek

The annual ICaMB 2nd year PGR Talks Day was held at the Research Beehive in November 2013

Every year, we give our 2nd year Phd students to present their research in a relaxed, informal setting to their peer group and to the incoming 1st year students. The purpose of the event is two-fold:

– provide 2nd year students with a new presentation skill of giving a research talk to an informed but non-expert audience

– give 1st year students  an illustration of the diversity of the science that is done in ICaMB and an idea of where their own research should be in one year’s time when it will be their turn to speak.

This year’s talks on eukaryotic biology ranged from whole organism mammalian physiology (“The effect of neuromodulatory medication on the oral mucosa”, Mustafa Al-Musawi, Jakubovics lab) to single cell yeast genetics (“The role of the CST complex in telomere integrity, Kate Clark, Lydall lab)].

Jack Stevenson presents his work on copper metabolism in S. aureus

A key aim of basic bioscience research carried out in ICaMB is that it underpins our understanding of the molecular basis of disease and disorder and informs future translational biomedical approaches. This aim was strongly evident with talks on mitochondrial translational defects in encephalomyopathy (Maria Wesolowska, Lightowlers lab), the molecular basis of disease caused by non-invasive enteric pathogens (Oli Amin, Kenny lab), the role of the oxidative stress response in mediating fungal infections (Melanie Ikeh, Quinn lab), the molecular basis of “ribosomopathies”- human disorders of ribosome dysfunction (Loren Macdonald, Watkins lab), the effects of Resveratrol (Suzanne Escome, Ford lab) and DNA methylation (Joy Hardyman, Ford lab) on age-related genes, and on the role of membrane transport proteins in renal stone disease (Sarah Rice, Thwaites lab). The theme was extended with talks on how dysfunction in metal ion homeostasis in cells plays a key role in disease and disorder, for example calcium signals in neuroblastoma (Claire Whitworth, Cheek lab) and copper in Alzheimer’s disease (Eliona Tsefou, Dennison lab). Copper metabolism in lower eukaryotes was discussed in a talk on copper trafficking in yeast (Kerrie Brusby, Dennison lab) and in prokaryotes by talks on copper binding sites in Bacillus subtilis (Gianpiero Landolfi, Dennison lab) and Staphylococcus aureus (Jack Stevenson, Waldron lab).

The evolution of eukaryotic cells, their genomes and organelles, is also of great interest to ICaMB researchers who collaborate with, among others, the Natural History Museum in London. One talk described the development of better methods, based upon likelihood and Bayesian approaches, for phylogenetic analysis of molecular data (Svetlana Cherlin, Embley lab). The aim is to improve the reconstruction of phylogenetic trees relevant to understanding the early evolution of eukaryotes and the origins of eukaryotic genes.

Another illustration of the diversity of ICaMB research is that laboratories are also engaged in the development of new technological strategies for biomedical research. This was demonstrated by talks on the development of a primary tissue culture model system that can be used to identify the renal toxicity of new therapeutic drugs (Sarah Billington, Colin Brown lab), a simplified detection process for aggregation in the manufacture of biotherapeutics (Alysia Davies, Lakey lab), and on the use of natural antisense transcripts that may lead to improved gene silencing strategies in clinical applications (Monica Piatek, Werner lab).

Sarah Shapiro discussing her work on gut microbiota

The Centre for Bacterial Cell Biology in ICaMB is at the forefront of research into fundamental aspects of the cell biology and biochemistry of bacteria. Research provides scientific insights crucial for the discovery and development of new antibiotics, as well as providing solutions to a huge range of industrial and environmental problems through the emerging discipline of synthetic biology. This focus was reflected by talks on bacterial cell wall peptidoglycans (Adam Lodge, Vollmer lab) and D-alanine (Karzan Sidiq, Daniel lab), on system noise in the transcription of negatively regulated bacterial genes (Thomas Ewen, Hamoen lab), on the bacteriocin colicin (Daria Stroukova, Lakey lab), on cell wall deficient bacteria (L-forms; James Brown, Errington lab) and on the role of dental plaque bacteria in biofilm formation (Jill Robinson, Jakubovics lab). The theme was advanced with two talks on complex glycan recognition, acquisition and degradation by human gut bacteria (Sarah Shapiro, Bolam lab; Max Temple, Gilbert lab). Results of this research have applications in a number of areas including the development of biofuels derived from plant cell wall material and in personalised nutrition approaches to optimise microbiota function for the benefit of human health.

Students chatting about the talks and their research

This opportunity to talk about science and to engage with peers in a semi-formal environment, with no academic staff, is invariably voted by 1st and 2nd year students as their most favoured ICaMB event of the year. This year was no different. With 26 speakers and around 50 attendees in each of the 4 sessions, ICaMB students are clearly voting with their feet!

 

 

Dr Tim Cheek is the ICaMB Postgraduate Tutor.

If you are interested in applying for a PhD studentship in ICaMB more details can be found at http://www.ncl.ac.uk/camb/study/postgraduate/index.htm


Links

PANIC: the postgraduate network of ICaMB http://www.societies.ncl.ac.uk/panicicamb/index.html

Postgraduate Opportunities at ICaMB http://www.ncl.ac.uk/camb/study/postgraduate/index.htm

 

ECRs at ICaMB: Solving 3D puzzles

 

by Dr Paula Salgado

After nearly one year editing the ICaMBlog, the time has come for me to tell you about my science and work since I joined ICaMB almost 18 months ago.

The fact that it has been 18 months since I moved up North to establish my own research group seems to have snuck up on me… Don’t get me wrong, so much has happened that, if anything, it’s surprising it all took place in 1 and a half years. At the same time, the feeling of a new adventure is still there.

Science is a constant adventure to seek new knowledge, to understand new mechanism, to see new things. In my case, to see into the very core of life’s machines: proteins. I use X-ray protein crystallography to probe the structure of proteins. It’s a bit like solving a puzzle: fitting the pieces of information together until we have a 3D view of the protein.

It is actually fitting that my blog post is the first ICaMB publishes in 2014 as this is the International Year of Crystallography. I could write a lot about it, but for now, I’ll leave you with an amazing video made by the Royal Institution that explains it all – in cartoons! If you want to know more about Crystallography, the Ri has a great collection of videos there, including Prof Stephen Curry’s Friday Evening Discourse, which I strongly recommend.

Freezing protein crystals for data collection at Diamond Light Source. H&S warning: liquid nitrogen is a hazard and we do handle it safely. At this point, I was just dipping the crystals into a small volume, all other procedures handling larger volumes involve wearing appropriate protection.

As a protein crystallographer, I’ve always been interested in proteins that have a relevance to human disease and used this technique to understand their structure and function. In the last few years, I’ve worked on proteins from human pathogens associated with hospital acquired infections, particularly Clostridium difficile and Candida albicans. However, protein structures don’t necessarily give us all the answers and they must be complemented with biochemical studies, as well as in vivo experiments. So my long term goal has become to establish a Structural Microbiology group, where we focus on structure determination of key proteins and complexes involved in pathogenicity as well as on their functional in vivo characterisation.

This is a challenge as it means stepping out of my structural biology comfort zone into the world of microbiology and cell biology. Not that I haven’t stepped out of my comfort zone before – if anything, those are areas that featured strongly during my undergraduate training as a Biochemistry student at the University of Porto in Portugal. In those days, choosing to do protein crystallography as my undergraduate project was the big step into the unknown. A trend that continued as a post-doc, when I joined Dr Cota and Prof Mathews group, a Nuclear Magnetic Resonance (NMR) lab at Imperial College, learning a completely different approach to protein structure determination. And just before coming to ICaMB, I worked in Prof Fairweather’s microbiology lab and always tried to learn a bit about the techniques others were using. So the current idea of bringing structural biology and microbiology expertise together in my lab is the natural evolution of these experiences.

C. difficile cells (green rods) lining the microvilli of the human gut. © Wellcome Trust (CC-BY)

Since joining ICaMB, I’ve focused on 2 main projects, both involving proteins from C. difficile. This spore forming strict anaerobe is resistant to most antibiotics and colonises the gut of individuals whose microbiome has been disturbed by these drugs. It is the most prevalent cause of gastrointestinal infections in hospitals and is a major cause of morbidity and mortality in the hospital environment. Despite recent decreases in the number of deaths and infections as hygiene procedures have improved in the UK, over 1600 people died in England and Wales in 2012 due to C. difficile infections (CDI). It also causes a huge burden to health systems, with an estimated €3,000 million per annum costs in the EU.

C. difficile disease symptoms are caused by the toxins it releases in a process that has been extensively studied over the years. However, the mechanisms of colonisation of the gut and spore formation are poorly understood. So we have been focusing on proteins involved in these two mechanisms.

Firstly, I’ve been trying to determine the structure of SlpA, the main protein constituent in C. difficile S-layer. S-layer is a paracrystalline coat that covers the cell and is presumed to act like a defense mechanism, as well as being involved in gut colonisation. This work, initiated a few years ago in Prof Fairweather’s lab is now a joint collaboration between our two labs and Dr Fagan, at Sheffield University.

SlpA crystals viewed under polarised light (protein crystals are birefringent, unlike salt crystals)

 

 

As this protein has tendency to form 2D paracrystalline layers, getting well ordered 3D crystals required for X-ray crystallography has been a challenge, but I have now succeeded in obtaining good crystals. However, other hurdles still need to be overcome to get a structure – but we are getting there!

 

 

Our lab: Adam Crawshaw and Paula Salgado

Last year, Adam Crawshaw joined my group as a BBSRC Doctoral Training Programme (DTP) student and we started a new project, looking at a complex between two membrane proteins that are essential for spore formation. As spores are the infectious agents, revealing the molecular details sporulation is important to understand the pathogenicity and infection cycle of C. difficile.

SpoIIQ and SpoIIIAH localise at the membranes of the forming forespore. Green: Membrane; Red: SNAP-tagged proteins.

When spores are first formed, a small cell (forespore) is engulfed by the larger mother cell, physically isolating it from the environment and nutrients in the medium. So, for the forespore to fully mature, it needs a nurturing channel to the mother cell. The two proteins we are studying  – SpoIIQ from the forespore membrane and SpoIIIAH from the mother cell membrane – create this channel. We have already successfully produced recombinant versions of the proteins and shown their interaction in vitro. In collaboration with Prof Henriques at ITQB, Lisbon, we also established their localisation during C. difficile spore formation. Next: crystals! But we are also investigating potential enzymatic activity both in vitro and in vivo, to bring the structure and biology together.

It has been an exciting year and a half – a steep learning curve with many new tasks, from supervising students to managing a lab and teaching undergraduates and postgraduates. The adventure continues, with new challenges and exciting discoveries ahead.

 


Links

International Year of Crystallography http://www.iycr2014.org/

Royal Institution Crystallography gallery http://richannel.org/celebrating-crystallography

Office for National Statistics (Clostridium difficile data) http://www.ons.gov.uk/ons/rel/subnational-health2/deaths-involving-clostridium-difficile/2012/index.html

European Centre for Disease Intervention and Control on Clostridium difficile  http://www.ecdc.europa.eu/en/healthtopics/healthcare-associated_infections/clostridium_difficile_infection/pages/index.aspx

BBSRC Doctoral Training Programme http://www.ncl.ac.uk/fms/dtp/