ICaMB goes away for a day

by Phil Aldridge

As scientists, it is critically important to prevent ourselves from becoming isolated in our own specialised world , as maybe, just maybe, the best person to help solve the scientific riddle you have been fighting with works just down the corridor. Finding that person is enormously helped by working in a vibrant and open community. This is why, once in a while, coming together with your colleagues to discuss the science we are pursuing is vital. This is something we have always tried to nurture in ICaMB . On a personal note it was one of the key factors that made me decide to accept the offer of the lectureship I interviewed for 10 years ago!

So, to our ICaMB Away Day held on Monday 14th October 2013 at the Vermont Hotel in downtown Newcastle. A new focus for the event this year was to hear primarily from the post-docs and PhD students about the work they are doing. In addition, we also featured talks from three of our new PIs, Owen Davies, Yulia Yuzenkova, who was recently awarded a Royal Society University Research Fellowship and Bert Van-Den-Berg.

A unique aspect of ICaMB is the diversity of the science we do and this is always a major take home message when we get together during our away days. This year, talks ranged from some fascinating work using bioinformatic analysis to interrogate the deep realms of evolution all the way up to the significance of where one little helix fits into a protein structure. Ah the joys of science…

Another way to view our away day is to focus on the range of techniques we all employ. The day was opened by Henrik Strahl* from CBCB, who is doing some elegant work with the super resolution microscope we have housed in the Baddiley-Clark building. Incidentally these microscopes are available for anyone in ICaMB to use and get excited about, not just Henrik.

Sometimes, to get to the bottom of our inquisitiveness, we require some BIG science. During our away day we heard from Simon Cockell, Arnuad Basle and Peter Banks about three opportunities we have in Newcastle to take our science and its analysis to that level using high throughput screening and bioinformatics analysis.

Arnuad gave a brief overview of how the Structural Biology lab has been coordinating a wide range of projects, with an impressive collaborators slide that was a who’s who of ICaMB.

Simon highlighted three large ICaMB data analysis projects he has been involved in from the Bioinformatic Support Unit. He also used the chance to get rather excited about the recent developments that has allowed the BSU to begin proactive recruitment, to bring in, as he said, “A half a dozen people to do a dozen peoples work, rather than two doing it all”

Peter then introduced the new faculty high-throughput facility that has been developed out of the work he has done with David Lydall. Hearing these talks can stimulate ICaMB members to look for ways to exploit these facilities to benefit their own research – exciting times, if you have the money of course.

Finally we come to the PhD students. Instead of the typical format of more talks, the organising committee this year invited our students to attempt a format growing in popularity termed “The 3 Minute Thesis.” This was ICaMBs first experience of this, although our colleagues in ICM had introduced it at their away day earlier in the year.  Hmm, maybe an opportunity for some friendly cross faculty competition? This format requires a student (or PI) to get across the message of their work in exactly 3 minutes, with the timing being strict and the talker being stopped at exactly 3 minutes. Eight students stood up to the challenge and we experienced a range of approaches to get their points across. Congratulations go out to all eight, especially Daira from Jeremy Lakey’s lab who won the judges approval with her demonstration of colicin action with two balloons, some sticky tape and a scary looking needle.

So all in all a great and successful day out for ICaMB, we heard some fantastic science, were able to be social and meet each other while discovering that what you really need to know to win the ICaMB quiz is the maiden name of Cheryl Cole. We have to acknowledge the excellent job done by our quizmaster, Harry Gilbert, although we suspect that Anne Robinson’s job is safe for now. A final big thank you must go to the organising committee who coordinated the whole event (the blog team are just reporting what happened). Well done Alison Howard, Dave Bolam, Liz Veal, Adam O’Neil and to our Director Bob Lightowlers.

*Congratulations also to Henrik Strahl, who a couple of days after his talk was awarded a Newcastle Biomedicine Barbour Fellowship

ECRs at ICaMB: For he’s a jolly good (RS) Fellow

As you saw from our post a couple of weeks ago, ICaMB has recruited several new PIs. To make sure we all know more about them and their research, we decided to have a series specially dedicated to them: Early Career Researchers (ERCs) at ICaMB. First in the series is Dr Kevin Waldron.

by Dr Kevin Waldron

As some of you will already know, I was awarded a Sir Henry Dale fellowship in 2012. This is a new funding scheme for early career researchers, which is co-funded by the Wellcome Trust and the Royal Society. The scheme provides exceptional research support for fellows, including funding a postdoctoral research assistant for the duration of the project (5 years initially, with potential extension for a further 3) as well as all direct research costs, with the aim of supporting the researcher while they forge an independent research career and carve out their research niche. As a result they are highly coveted and extremely competitive – the interview at the Wellcome Trust in July 2012 was probably the most intimidating experience of my career. My award was one of the very first round, in which 10 awards were given from a pool of about 100 applications.

Enjoying the sights of Ha Long Bay (Vietnam)… and doing some deep thinking about my science, of course…

Though the grant was awarded in Summer 2012, I only activated the grant in May 2013 (primarily so that I could swan off on an extended holiday travelling round South East Asia – but that’s another story). Since May there have been two new additions to my lab team; Emma Tarrant, a postdoctoral research associate funded by the fellowship grant, and Anna Barwinska-Sendra, a new PhD student. This combination of good funding and great new people will allow us to really get our teeth into our research question over the coming years, free of the hassle of grant writing and worrying about where the next funds are coming from.

 

I have been studying bacterial metal homeostasis since I started my PhD with Prof. Nigel Robinson (now in Durham), way back in 2003. During that period I studied cyanobacteria, but my current research is focused on the Gram positive mammalian pathogen Staphylococcus aureus. S. aureus has become a major medical problem in recent decades due to the rise of strains that are resistant to multiple conventional antibiotics, with the term “superbug” and the acronym “MRSA” entering the popular consciousness – see for example here, here and here. The organism is particularly problematic in hospitals, where it causes significant morbidity and mortality (see for example these UK and US studies). Though infection control measures introduced in hospitals are proving successful in reducing the number of S. aureus-related deaths, both the prevention and treatment of hospital-acquired infections remain major burdens on patients and on the NHS budget. S. aureus is also problematic in farm animals, being a major cause of bovine mastitis and of lameness among broiler chickens.

My favourite metal

One intriguing new approach to prevention of infection in such settings is the use of solid copper or copper-containing alloys. Copper surfaces show wide-spectrum antimicrobial activity and are certified by the US EPA as antibacterial and ‘self-sanitising’. Multiple trials have shown that these materials can reduce bacterial copper load on touch surfaces in hospitals (see here for example), and the effects on disease transmission are currently being tested. In fact, this is not a new approach at all: as this YouTube clip explains, copper has been used since ancient times to sterilise drinking water and to treat minor ailments, even being mentioned by Hippocrates in ~400 BC. Copper is the active ingredient in numerous agricultural fungicides including Bordeaux mixture, in use since 1885.

The mechanisms by which copper, either as metal salts or as solid metal surfaces, kills bacteria are unknown. Dissolved copper ions are thought to play an important role in the killing mechanism even from solid copper surfaces. In fact, the toxicity of excess concentrations of essential metal ions (as opposed to non-essential metals such as lead and mercury) has been historically under-studied and has merely been seen as a confounding factor of studies of normal metal homeostasis. Copper is redox-active, a potent Fenton catalyst, and therefore may catalyse the production of reactive oxygen species in vivo. It is also at the top of the Irving-Williams series, meaning it will bind extremely tightly to proteins, potentially having deleterious effects on their function when present in excess.

Our goal is to identify and understand these toxicity mechanisms, both to shed light on new aspects of metal homeostasis and to find better ways of exploiting this toxicity for medical and commercial applications. To do this we’re going to use a combination of multiple experimental approaches in collaboration with a number of world experts in diverse fields. We will use proteomic methods to identify S. aureus proteins that become aberrantly associated with copper under high-copper growth conditions, and then characterise the functional effects of those aberrant associations using traditional biochemistry and molecular genetics. We will combine this with metabolomics studies of the effects of copper toxicity on bacterial metabolism. Finally, we will use genetic screens to identify mutant strains that display increased copper resistance. Together, this should give us a comprehensive view of the effects of copper toxicity on the cell, with the aim of elucidating the multiple mechanisms by which excess copper interferes with normal function.

The Waldron lab group: Jack Stevenson, Emma Tarrant, Anna Barwinska-Sendra, Stuart York and Kevin Waldron (left to right)

 

So we’re just starting off on a long-term quest, with lots of experiments to keep us busy for the next few years. It’s an exciting time in the Waldron lab.

 

 

 

 


Links

Sir Henry Dale Fellowships   http://www.wellcome.ac.uk/Funding/Biomedical-science/Funding-schemes/Fellowships/Basic-biomedical-fellowships/WTDV031823.htm
Wellcome Trust www.wellcome.ac.uk/index.htm
Royal Society www.royalsociety.org
US EPA www.epa.gov/pesticides/factsheets/copper-alloy-products.htm