Category Archives: General

ECRs at ICaMB – Green transcription: how studying Cyanobacteria could change the world

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In the latest of our series on the Early Career Researchers of ICaMB we asked Dr Yulia Yuzenkova to tell us about her research and the route that took her from a PhD in Moscow to being awarded a Royal Society University Research Fellowship in Newcastle.

Yulia
Dr Yulia Yuzenkova

My early training was in Moscow, firstly as an undergraduate at Moscow State University and then for a PhD from the Russian Academy of Sciences. However, during my PhD I moved to the USA to study at the Waksman Institute (Rutgers University) with Prof Konstantin Severinov, where I was also a postdoc. My work in the laboratory was dedicated to the molecular mechanisms of inhibition of bacterial transcription by antibacterial peptides and small proteins from viruses. Transcription is the first step and critical regulatory checkpoint of gene expression. In all living organisms transcription is performed by multi-subunit RNA polymerases (RNAP). The central role of transcription in cellular metabolism and the presence of domains specific for bacteria make RNAP an obvious target for antibiotics. Yet, for decades, only one inhibitor of RNAP, rifampicin, has been used in the clinic to treat tuberculosis, while only recently, in 2011, lipiarmycin (fidaxomicin) was approved to eradicate Clostridium difficile. Two is a very small number, but this indicates that there is a good probability of finding new drugs that also work by targetting RNAP. Apart from their clinical significance, antibiotics and inhibitors of transcription in general have been proven to be very efficient molecular tools (see “RNAP details” below for more info).

During my second PostDoc in the lab of Prof Nikolay Zenkin in Newcastle, I have focused on the mechanisms controlling the fidelity of transcription. The copying of genetic information by RNAP is far from being absolutely precise, and RNAP whimsically dislikes reading some DNA sequences, resulting in ‘pauses’. RNAP is able to correct its own mistakes using a proofreading mechanism and the help of small proteins called transcript cleavage factors (explained in detail below). It seems to be important to have at least one cleavage factors; otherwise, the RNAP molecules stop, resulting in “traffic jams” as trailing molecules keep moving and bump into it.

Batch culturing of cyanobacteria

Batch culturing of cyanobacteria

It was therefore a big surprise for me to learn that one large group of bacteria, cyanobacteria (details below), do not encode anything even remotely resembling cleavage factors. I started to look for an explanation for this extraordinary fact. Are there any factors that might compensate for the absence of cleavage factors? Is cyanobacterial RNAP so accurate and at the same time processive that it does not need them? In searching for the answer, I realised that almost nothing is known about the molecular details of transcription in cyanobacteria, and so I decided to apply for a Royal Society University Research Fellowship to try to answer these questions.

Microscopy image of membrane-stained cell of Synechocystis sp 6803

Microscopy image of membrane-stained cell
of Synechocystis sp 6803

In performing preliminary experiments for my application, I became fascinated with cyanobacteria, as they are truly amazing organisms to work with. They are the only prokaryotes that exhibit the classic circadian clock, and are the bacteria with the most complex intracellular organisation. Moreover, they are one of the most ecologically important groups on Earth. They live everywhere where sunlight is available and produce 30% of atmospheric oxygen; some can even convert inert atmospheric nitrogen into a digestible form.

 

The 2D projection of the membrane structure of cyanobacterium reminds me of a labyrinth

The 2D projection of the membrane structure of cyanobacterium reminds me of a labyrinth

With my Royal Society University Research Fellowship I am planning to investigate the molecular details of the transcription machinery and will look for novel transcription factors that regulate this process. I am also going to test the metal requirements of cyanobacterial transcription, because metal composition of cyanobacterial cells is very different from other bacteria to suit the need of photosynthesis. Another fascinating question is how fast in the cyanobacterial cell, which is tightly packed with photosynthetic organelles, can molecules find their way through the membrane labyrinth.

 

 

The nitty-gritty science:

RNAP in detail:

Inhibitors of RNAP as molecular tools for understanding its functions. A wide range of targets of known inhibitors is mapped on the structure of bacterial RNAP. We contributed to understanding the modes of action of inhibitors marked in bold.

Inhibitors of RNAP as molecular tools for understanding its functions. A wide range of targets of known inhibitors is mapped on the structure of bacterial RNAP. We contributed to understanding the modes of action of inhibitors marked in bold.

Studying the antibiotics and inhibitors modes of action have helped us and other groups to discover previously unknown functions and structural domains of RNA polymerase. For example, work on rifampicin shed light on geometry of the RNA exit path, long before the crystal structure of RNAP was solved. Moreover, streptolydigin led to the discovery of the novel catalytic domain, while microcinJ25 confirmed the proposed entry channel for substrates and tagetitoxin provided insight into the mechanisms of RNAP translocation along the template.

Newly synthesised RNA participates in the proofreading  in a ribozyme-like manner. This method of proofreading, probably a remnant from the distant past, is extremely slow. To accelerate proofreading (and to escape from pauses), all 3 domains of life encode non-homologous, but very similarly folded, small proteins called transcript cleavage factors. In E.coli, GreA is an example of a protein that fulfils this role. Some bacteria have several homologs of GreA (in E.coli there are at least 6). It seems to be important to have at least one, because if these cleavage factors are depleted in the cell, the RNAP molecules on the actively transcribed genes stop, obstructing transcription, but also the chromosomal replication machinery moving along the same DNA.

Cyanobacteria:

Cyanobacteria have been hailed as future photobioreactors.  Indeed, when supplied with little more than tap water and light, engineered cyanobacteria can produce all sorts of compounds from sunscreen to biofuels. Cyanobacteria can also be used for environmental applications such as greenhouse gas fixing and cleaning water from industrial pollutants. These initiatives, however, are compromised by slow growth of cyanobacteria and limited knowledge of their basic biology. By putting more effort into research, the potential abilities of cyanobacteria can eventually be harnessed on the industrial level. With this we could make a giant leap towards a future “greener” economy. With a little bit of imagination, it is not hard to envisage cyanobacteria helping humanity to colonise new worlds, and to permit them to inhabit the first lunar and martial greenhouses in not so distant future.

Dr Yulia Yuzenkova’s ICaMB website: http://www.ncl.ac.uk/camb/staff/profile/yulia.yuzenkova

Royal Society University Research Fellowship: https://royalsociety.org/grants/schemes/university-research/

Recruiting the next generation of ICaMB scientists

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In 2013, we created the IRES fellowship scheme to recruit potential new Principal Investigators to ICaMB. Now Faculty wide and renamed the Newcastle University Research Fellowships (NURFs) a new round of recruitment has just opened. Here, Neil Perkins reflects on the thinking behind the IRES scheme and why recruitment of early career researchers is so crucial.

ICaMBatNewcastle NURF advert final

It’s a moment for sober reflection when you realise that you can no longer be classified as a ‘young scientist’ and have now become part of a problematic group of rapidly ageing professors. Although when Bob Lightowlers, the ICaMB Director, told us a few years ago that we only had one Principal Investigator (PI) under the age of 40 I think we were all a bit shocked.  Only one? Speaking as one of that cohort of over 40’s, I would of course defend our ability to still perform cutting edge science and stay on top of the latest developments in technology and social media. Well some of us anyway. However, as with many things, balance is important. Early career (to use the formal term) PIs bring vibrancy and energy to a department, generate new ideas and very importantly also challenge ingrained departmental behaviour. At least that’s how I like to fondly remember my time as a new PI in Dundee. I was probably just a pain in the neck.

To get back to the point, we had a problem and needed to find a way to fix it. In an act of skilful diplomacy, Bob Lightowlers managed to persuade the faculty leadership that we could begin the process of new recruitment immediately and that this would be funded by proleptic appointments. Yes, I had to go and look that up when I first heard it (after nodding my head as if I knew what he was talking about). In practical terms this meant that because we could anticipate retirements in future years, this future funding stream would be used to create new positions now. I assume the numbers add up.

We wanted to do something different with these new positions. In recent years, fellowships have become an increasingly popular mechanism to kick start someone’s career as a PI. They offer a transition period, where the new PI is protected from too onerous a teaching load (although all our new appointments will do some teaching), enabling them to focus on establishing an independent research programme. From the perspective of management, they provide the opportunity to assess whether a new appointee is really suited to this career before being offered a permanent position.  So at the beginning of 2013 we created the Independent Researcher Establishment Scheme (or IRES). In the first instance this involved the creation of three 5-year fellowships.  Importantly, after a rigorous assessment period, these should all lead to full academic positions with open contracts. It should be emphasised that there is no element of competition between our new IRES fellows (apart from some hopefully friendly rivalry).  We want them all to succeed and get permanent positions.

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When it came to recruiting the IRES fellows we were very conscious of the fact that we were recruiting future colleagues so we wanted to do more than the fashion parade that often passes for the interview process for new lecturer appointments at some UK universities (see rant to the right). We had 80 applications for the 3 IRES positions, many of which were of a very high standard. From this, after some heated debate by the ICaMB Research Committee, we whittled this down to a list of ten, all of whom were invited to Newcastle for an informal visit, where they gave a seminar, met colleagues and participated in a ’round table’ discussion about their future research and funding plans. We took them out to dinner and put them up in a hotel. Not quite the full Philip Cohen Dundee bird watching experience but a step in the right direction I think. From this list of 10 we created a final short list of 6, who all returned for a formal interview and from these we appointed 3 IRES fellows. All our IRES fellows are now in place and you can read about who we appointed here, in a previous ICAMBlog post. Will it work? Only time will tell but the early signs are very promising. We are very proud that our first arrival, Owen Davies, was recently awarded a prestigious Royal Society/Wellcome Trust Henry Dale Fellowship (more on this in the future). Our IRES appointments also join our growing cohort of successful early career PIs that includes Paula Salgado (recently awarded an MRC New Investigator Research Grant), Kevin Waldron (also recipient of a Royal Society Henry Dale Fellowship), Yulia Yezenkova (Royal Society University Research Fellowship), Suzanne Madgwick (Wellcome Trust Career Re-entry Fellow), Heath Murray (Royal Society University Research Fellow), Joao Passos (BBSRC David Phillips Fellowship) and Claudia Schneider (Royal Society University Research Fellow). I was very happy to hear that they had recently arranged a trip to the pub to begin the process of plotting and scheming.

The author, in his youth, plotting and scheming with other new Dundee PIs in our traditional meeting place.
The author (3rd from left), in his youth, plotting and scheming with other new Dundee PIs in our traditional meeting place.

Imitation is the sincerest form of flattery, although not to be encouraged in undergraduate essays or academic publications, and now the ICaMB IRES scheme has been transformed into the Newcastle University Research Fellowships. Essentially, with some tweaking, our IRES fellowships have now been adopted by the entire Faculty of Medicine in Newcastle. Despite this, recruitment will still be handled by the Institutes themselves, so if you are reading this and are interested in becoming an ICaMB PI, then please get in touch. Here is our advert (ICaMBatNewcastle NURF advert final – pdf) and informal enquiries may be made to:

Bob Lightowlers, Institute Director (robert.lightowlers@ncl.ac.uk)

Janet Quinn, Search Committee (janet.quinn@ncl.ac.uk)

Kevin Waldron, Institute Fellowship Advisor (kevin.waldron@ncl.ac.uk)

Importantly, ICaMB is committed to the Athena SWAN Charter for women in science as detailed on our web site.

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The opinions in this article are those of the author and not necessarily those of ICaMB or the Faculty of Medical Sciences at Newcastle University. Although the author thinks they really should be. 

Antisense Science: A Science Blog by Students

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Blogs are now a widespread science communication tool, with many researchers taking to the blogosphere to discuss the latest scientific discoveries, explain the basic concepts in their research field to a wide audience or just talk about science and scientists. Our 3rd year bioscience students have done just that, and this week we have a guest post prepared by them.

 

by Antisense Science

Antisense Science is a science blog founded by a group of 3rd year bio-scientists from Newcastle University. As a team, we recognise that science is not as accessible to the general public as it should be.  We therefore make it our primary aim to translate complex scientific principles and research articles that interest us personally, into topical, thought provoking blogs accessible to everyone.

Our project is small but our ambition is big! Since our founding in October 2013 we have published 58 articles covering psychoactive baths salts, human evolution and the neurobiology of love, to name a few, and with a growing following (we’ve had over 6000 hits since inception) we were thrilled to be given the opportunity to guest post on ICaMBlog. As Newcastle University students, our interest in research was stirred by the professors at Newcastle University, including those who founded this blog. With planned guest posts focusing on research by Prof Rick Lewis among others, maybe YOU will feature on Antisense Science in the near future! We foresee (we hope!) that our blog can form a bridge between researchers here at Newcastle and the student body, raising awareness of what is actually being discovered right under our noses. By forming mutually beneficial collaborations, we hope to diversify and grow our following and expose our current readers to a continual stream of stimulating articles which never fail to pique the interest of the curious.

Meet the Antisense Science team

Meet the Antisense Science team

Currently, we have a total of 7 writers, all of whom enjoy sharing the intrigue of the latest developments in science, from biochemistry to microbiology (and even physics) and we have no plans of stopping. Although many of us will be moving on from our BScs to ever greater things, Antisense Science will remain and we are even in the process of recruiting further up and coming bio-scientists as writers (keep your eyes peeled for blogs from first year students Bethany Lumborg and Lucy Gee, as well as our fellow third year Emily Lawson and a multitude of guest posters from across the student body). The future looks bright and we’re very glad with the progress we have made thus far!

For an example of what we do, here is an article on depression written by our very own Joe Sheppard. We hope you enjoy it!  If you ever want to be involved in any of our projects feel free to drop us a message.  We also have Facebook (www.facebook.com/antisensescience) and Twitter (@AntisenseSci) so there are plenty of ways to keep in the loop.

 

The Confounding Contradictions of Depression

If you currently have or have had depression then you may already be able to tell your MAOIs from your SSRIs, but if you haven’t then what you read here might actually help. Knowledge is power and I believe learning a little something about depression could contribute a bit of control to an otherwise daunting and often underestimated medical condition.

Depression is perhaps the ultimate “common complex disorder”. Unlike pathogens or mutations that affect physical body tissue, depression is a condition that alters the very consciousness and emotional state of an individual making it a truly unique affliction. Throughout the course of our lives 1 in 5 of us will experience depression or anxiety of some kind, yet the majority of people conceive depression  simply as a disease of “sadness” when the truth is much more complex. “Anhedonia“, an inability to feel joy in anything and “congruent memory bias”, the inability to remember or altered recall of specific memories, are extremely common cognitive behaviours in depression that we often inflict upon ourselves on a day to day basis.

It may surprise you to know that modern science can say with little certainty what neuro-physiological changes initiate depression, and linking those that we do think are involved to the broad psychiatric manifestations seen in cases of depression is even harder as human experience and consciousness is beyond the understanding of molecular neuroscience (and by extension, definitely me). But from the murky depths of our own minds patterns do emerge, and as such there are a few good theories out there.

Rather confusingly the best fitting theory of depression is actually based on the drugs WE ALREADY USE to treat it, not a common theme in medicine, I might add. “The monoamine theory of depression” states that depressed brains have reduced signalling between neurons via a group of specific chemical neurotransmitters called monoamines. Two in particular called 5-hydroxytryptophan (hereafter referred to as serotonin) and dopamine are released into a synapse to induce electrical signals between neurons in the midbrain. These two neurotransmitters and the resulting electrical signals are most notably perceived as feelings of joy, euphoria, reward and attention. And there is some evidence to back this up: depletion of tryptophan, an amino acid essential for serotonin synthesis in the brain, caused mood congruent memory bias, and altered reward-related behaviours. Biochemical evidence exists too, abnormalities of the protein that binds serotonin in the brain called the 1A receptor have been noted in multiple brain areas of major depressive disorder (MDD) patients. Why does serotonin decline in patients with depression? Well, search my pockets, you will find no answers.

Rather reassuringly this hasn’t stopped treatment of depression at all, and several drugs for which the theory is named are all targeted at increasing serotonin, and so good feelings, within the brain. The so named selective serotonin re-uptake inhibitors (those “SSRIs” I snuck in earlier, such as fluoxetine and sertraline) are the most prescribed group of antidepressants and work in a way best aided pictographically:

Neuron

Schematic representation of neuron activity

Serotonin is synthesised in the presynaptic neuron from tryptophan, from here it is packaged into vesicles and upon nerve impulse firing (see previous article “ shedding light on neural networks”) is released in the synaptic cleft (the space between neurons).  Serotonin then binds to receptors on the postsynaptic neuron, stimulating a similar nerve impulse. However, serotonin is also able to control its own release: By binding to the 1A receptor on the presynaptic neuron it prevents continued release of serotonin, allowing the proposed channel protein SCL6A4 to re-absorb serotonin in the presynaptic neuron to be destroyed.

This is where SSRIs come in. Believed to bind to SCL6A4 and prevent the re-absorption of serotonin, it allows serotonin to remain in the synaptic cleft for longer and therefore stimulate nerve impulses in the post synaptic neuron for longer, and so increase the degree of monoamine signalling.

Let’s not forget our friend dopamine:

Dopamine too is a monoamine consistently found reduced in the blood of patients with depression, as a result of decreased synthesis and degradation in the brains of these patients. Neurons that signal using dopamine (as opposed to serotonin) are found in a region of the brain called the substantia nigra that degenerates during Parkinson’s disease. Interestingly the motor impairment (shaking) in this disease is often preceeded by major depressive disorder in 50% of Parkinson’s cases!

This brings me quite nicely to my final point. Since so little is known about the basis of psychiatric disorders their treatment has been almost purely symptomatic for the last 60 years. Thomas Insel, director of the US National Institute for Mental Health was quoted in 2013 as saying “In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain, or the quality of fever.” This was following the release of the 5th edition of the diagnostic and statistical manual of mental disorders (DSM-5), that diagnoses psychiatric conditions based on common symptoms presented by each condition. Despite the strong agreement with Insel by many psychiatrists that this method is outdated, the shift to a more objective and molecular diagnostic is years away given the outstanding complexity of these diseases. But keep the hope, recent booms in neuroscience research are a sure step towards a less archaic means of treating depression and other mental disorders.

A new approach spearheaded by the same Thomas Insel called “Research Domain Criteria” or RDoC is already doing just that by utilizing genomic sequencing technology, fMRI imaging techniques and cognitive science to develop an entirely new platform for diagnosis based on new data being attained all the time, rather than the laboured DSM-5 classification. While still in its infancy this new approach aims to start looking at broader groups for diagnosis rather than classification of different disorders by the symptoms they present. For instance, by looking at a group of patients with different disorders but all experiencing anhedonia will not only allow a greater insight into a unifying cause for these symptoms, but also speed up treatments in the future.

Of course, there are always two sides to each argument and depression does in some sense stand alone from other psychiatric disorders such as schizophrenia in that it imparts a greater emotional influence on the sufferer – if “precision medicine” were able to prescribe a pill for the treatment of emotional conditions, would you want it to? Of course this is a quandary we won’t face for some time, but worth a thought.

J.

Some interesting but by no means comprehensive reviews on depression, its far too huge for 3 articles!

Hasler G (2010). Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World psychiatry : official journal of the World Psychiatric Association (WPA), 9 (3), 155-61 PMID: 20975857

Martinowich K, Manji H, & Lu B (2007). New insights into BDNF function in depression and anxiety. Nature neuroscience, 10 (9), 1089-93 PMID: 17726474

Frances, A. (2013) One manual shouldn’t dictate US mental health research
(Accessed: 07/01/14).

One year of the ICaMBlog in numbers

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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

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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/

ICaMB PhD studentship opportunities

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PhD student recruitment season is upon us.  If you or maybe someone you know is interested in a doing PhD in Cell and Molecular Biosciences in a leading UK Research Institute (that happens to be based in one of the most exciting yet affordable cities in the UK), then read on.  This year we are giving you an early preview of the opportunities available in ICaMB and telling you a bit about who we are and what doing your PhD here with us has to offer.

ICaMB PhD students benefit from being in a dynamic and well funded research environment with access to state of the art technology.  Our research interests cover the cutting edge of bacterial cell biology all the way through to eukaryotic cell signalling and cancer research.  ICaMB investigators have been awarded £39.32M since 2008, which includes major funding from the Wellcome Trust, the ERC, BBSRC, The Royal Society, Cancer Research UK, Leukemia and Lymphoma Research and the Association of International Cancer Research.

 

PhD students do not exist on experiments alone and the ICaMB PhD student association PAN!C helps to facilitate social as well as scientific interactions.  You can read more about PAN!C in a previous ICaMB blogpost.

 

The recent 2nd year PhD student presentations

Below we have listed the MRes/PhD Studentships scheduled to begin in ICaMB in September 2014.  These are also listed on the ICaMB website, where they will shortly be formally advertised. Further details of the projects and guidelines on how to apply, will be posted in the next few weeks.  However, if you would like further details about the projects NOW you can contact the named supervisor directly or the ICaMB Postgraduate Tutor Dr Tim Cheek (email tim.cheek@ncl.ac.uk).  In exceptional circumstances, especially if the prospective applicant already has interviews arranged at other institutions, we can expedite and fast track the interview process (please contact Tim Cheek for more details if this applies to you). 

Eukaryotic Cell Biology

The last year has seen a lot of recruitment activity in ICaMB, one result of which was the appointment of three new PIs as part of our Independent Researcher Establishment Scheme (IRES). We introduced Dr Owen Davies, Dr Niall Kenneth and Dr Josana Rodriguez recently.  Doing PhD research with a new PI offers the chance to work at the bench directly with a young and enthusiastic scientist at the top of their game.  Many ‘first’ PhD students go on to achieve great things. There was great competition for our IRES positions and a PhD position with any of these new PIs promises to be a rewarding experience.

Title of Studentship: Uncovering the molecular basis of homologous chromosome synapsis by the synaptonemal complex during mammalian meiosis
Funding Source: BBSRC DTP
Supervisor: Dr Owen Davies (email owen.davies@ncl.ac.uk)

Title of Studentship: What are the protective roles of XIAP in the response to oxidative stress?
Funding Source: BBSRC DTP
Supervisor: Dr Niall Kenneth (email niallk@med.umich.edu)

Title of Studentship: Understanding microtubule dependent signalling in the generation of cellular asymmetries
Funding Source: BBSRC DTP
Supervisor: Dr Josana Rodriguez (email josanarsl@googlemail.com)

We also have PhD studentships available with Prof Brian Morgan and Dr Elizabeth Veal. Both PIs are investigating the important area of oxidative stress signalling (relevant to many diseases, including cancer) using the model organisms Saccharomyces cerevisiae and Caenorhabditis elegans and publish routinely in high impact journals, such as  Molecular Cell. A PhD in either lab provides an opportunity to work at the cutting edge of research into eukaryotic cell signalling.

Title of Studentship: How does the regulation of ubiquitin/ubiquitin-like pathways determine cellular responses to reactive oxygen species?
Funding Source:BBSRC DTP
Supervisor: Prof Brian Morgan (email brian.morgan@ncl.ac.uk)

Title of Studentship: Understanding how hydrogen peroxide signals control cell growth, survival and ageing
Funding Source: BBSRC DTP
Supervisor: Dr Elizabeth Veal (email elizabeth.veal@ncl.ac.uk)

Host-Microbe Interactions

The next two positions complement each other, with one exploring the host’s reaction to microbes while the second focusses on the microbe’s response to the host. Dr Judith Hall and Dr David Bolam are both key members of ICaMB and have a strong track record as PhD supervisors. So if you have an inclination towards exploring innate immunity or diving into the growing community of microbiologists interested in the microflora that interacts with us on a daily basis, maybe one of these two posts is for you.

Title of Studentship: Dissecting the role of the Dectin-1 Receptor in the Innate Defences of the Uro-genital Tract
Funding Source: Dr William Edmund Harker Foundation
Supervisor: Dr Judith Hall (email judith.hall@ncl.ac.uk)

Title of Studentship: Understanding how the mucosal layer is a microbial niche within the gut microbiota
Funding Source: BBSRC DTP
Supervisor: Dr David Bolam (email david.bolam@ncl.ac.uk)

Bacterial Cell Biology 

The final two positions are both located in the Centre for Bacterial Cell Biology, affiliated to ICaMB. You can read up on our work on bacterial cell biology in previous posts including our investigations with bulging bacterial cells to explain division, how we explode bacteria for science, or highlighting a recent paper from Nikolay published in the prestigious journal Science. In addition, Yulia Yuzenkova was recently awarded a prestigious Royal Society University Research Fellowship and her research was featured on the ICaMB blog.

Title of Studentship: Cyanobacterial transcription machinery
Funding Source: BBSRC DTP
Supervisor: Dr Yulia Yuzenkova (email yulia.yuzenkova@ncl.ac.uk)

Title of Studentship: Bacterial immunity and multi-drug resistance
Funding Source: BBSRC DTP
Supervisor: Prof Nikolay Zenkin (email nikolay.zenkin@ncl.ac.uk)

Please note that there are eligibility requirements for BBSRC DTP studentships (link to download pdf).

Typical ICaMB laboratory space

Links

ECRs at ICaMB: My Meiotic Journey

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In the latest of our series focussing on the new Early Career Researchers (ECR) in ICaMB, we feature Dr Suzanne Madgwick.  Suzanne recently returned to the lab after a career break by successfully applying for a Wellcome Trust Career Re-entry fellowship.  She tells us more about her science, her life and why coming back into science was always something she wanted to do.

 By Dr Suzanne Madgwick

After 6 years officially away from science I am thrilled to be back, almost 10 months in to my first fellowship position and about to supervise my first PhD student ….. though more than a little frightened by how fast the time is going! ICaMB has been a very positive and supportive place to come back to and the future looks bright for our growing meiosis team.

Not many PhD students get to ride horses as part of their project

I started out my meiotic journey not as a cell biologist, but as a Physiology and Nutrition student at the University of Leeds where I quickly found that the area of biology I am most fascinated by is the complexity, control, and number of systems a body has dedicated to reproducing itself. From my degree I went straight into a PhD here at Newcastle, in SAgE, with Dr Andrew Beard studying endocrine control of the developing reproductive system in cows. Whilst adolescent bulls are not the easiest experimental model to deal with, like most people I have very fond memories of my PhD. A definite highlight was a year of practical work carried out at a veterinary university in Canada, being able to round up my animals on horseback and drive oversized farm vehicles!

Brightfield image of an in-vitro matured metaphase II stage mouse oocyte showing polar body 1 (containing the waste chromosomes) from the first meiotic division. Approx diameter of the oocyte = 80um

Although I am proud of my PhD work, during this time my interests made a definite shift from whole animal reproductive systems to the molecular control of the reproductive cells themselves. Luckily, Professor Keith Jones (formerly of ICaMB) offered me a Post Doc position in his lab researching an arrest point in the life of a mammalian oocyte that maximises the window of opportunity for fertilisation. This was a successful time and we were able to publish a number of papers detailing the control of this arrest and how spermatozoa are then able to awaken an oocyte. I was left in no doubt that I had found not only the area, but also a method of research that I thoroughly enjoy being a part of.

Nearing the end of my post doc and armed with a pretty solid CV, I turned my interest to my own meiosis and made the decision to leave science on a high and spend a few years concentrating on bringing up a family. I always knew I would attempt a comeback, researching and bookmarking the Wellcome Trust Career Re-entry pages at the same time as I planned my exit.

Suzanne's research no longer requires access to a combine harvester

After 5 years of baby and toddler groups, and 2 confused little boys wondering why their mother suddenly started needing to go back to school (I was asked at one point if it was because I didn’t try very hard when I was at proper school the first time) I began regular visits to the lab and a period as full time mother / nocturnal grant writer. I can’t say any of this was very easy, but I also can’t imagine having the same enthusiasm for any other career. The support and advice I have had from both the Institute and the Wellcome Trust regarding career re-entry has been excellent. Taking a break from science was certainly the right decision for me. For anybody else considering this there are a number of ways for both men and women to re-enter a career in science, (in addition to the Wellcome Trust there is our own Faculty/Barbour Fellowship scheme, as well as the Dorothy Hodgkin and Daphne Jackson fellowships ).

The end stage of the application process was an interview at Wellcome Trust headquarters in London and whilst I tried to appreciate the privilege of being there in the first place, I have to agree with Kevin Waldron and say that it was also the most intimidating experience of my career. My second visit to the interview room for a Fellows conference in the summer was a far more relaxed and really a very inspirational meeting of both current and past Career Re-entry Fellows, including Newcastle’s Professor Helen Arthur who took a 10 year break.

Balancing a career and a young family is a certainly a tricky juggling act which I’m sure most parents have experienced. Attempting to work part-time in research is also pretty difficult (largely I admit a self-inflicted problem caused by the drive to try out the next experiment). I’m still working on this balance. Thankfully the Fellowship Scheme has the flexibility to be able to make changes to working hours and my children are already very interested in quizzing me about cells. I confess a great deal of pride when I recently overheard my 4 year old give a very basic yet accurate description of aneuploidy to his nursery teacher.

My current interest is in the events surrounding aneuploidy in female meiosis. Human oocytes have an extremely high failure rate, frequently resulting in an error in chromosome segregation, which is considered to be the leading genetic cause of birth defects and miscarriages.

Suzanne getting ready to inject oocytes using a mouth pipette*

In particular I plan to concentrate my research on unknown aspects of cell cycle control in mammalian oocytes through the first and most error prone of the meiotic divisions. Theories formed towards the end of my post doc along with more recent preliminary data have led to the hypothesis that an entirely novel mechanism of metaphase exit may exist in female meiosis; one which has not previously been noted through studies in mitosis. Our experimental approach is to use fluorescently-tagged gene constructs in real time live cell assays. mRNA encoding these constructs is microinjected into oocytes, resulting

in a fluorescent signal as a result of protein expression. Fluorescent expression and mRNA knock down experiments characterise the behaviour of resulting proteins. Of particular interest is, the targeting of the maturation promoting factor (MPF) component cyclin B1, which is crucially destroyed to allow chromosomes to segregate. A full understanding of how oocytes progress through cell division will help to explain why female meiotic cells do not have the same capacity to check and repair themselves as healthy mitotic cells do.

Intriguingly, like female meiosis, a failure to correctly regulate chromosome division is a major phenotype of virtually all cancers. Hopefully by investigating features of a cell cycle that appears to allow cells to proliferate despite division errors, my research will be of interest beyond meiosis and to the wider field of cell biology.

*mouth pipetting is considered to be a quick and accurate way of stripping cumulus cells and transferring delicate oocytes in minimal volumes of media. Glass Pasteur’s are drawn over a Bunsen burner and broken to give a pipette diameter of just a few microns above that of the oocyte.

ICaMB goes away for a day

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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

Thermolastics wins ACTION 2013

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Kate Clark is a PhD student in ICaMB who recently won first prize as part of the Thermolastics team at ACTION 2013.  Here she tells us what it was all about and how she found the experience

By Kate Clark

I’m a PhD student in David Lydall’s lab, and I was part of the ThermoLastics team that recently won ACTION 2013.

ACTION is an annual, EPSRC-funded, 6 month programme open to both postgraduate students and research staff (http://research.ncl.ac.uk/action2013/).  The aim of ACTION is to generate ideas from the Newcastle University research community to tackle societal challenges in the North East. This year, there were three societal challenge themes: sustainability, social renewal and changing age.  Participants were asked to create a social enterprise that addressed one or more of the challenge themes.  The programme started with a two-day residential, where teams were formed and business ideas were generated.  This was followed by a series of 1-day training labs, which introduced teams to key aspects of developing a business.

I formed a team with three engineering PhD students – Thomas Bohl, Eesha Raut and Amy Green.  Eesha and Amy are chemical engineers, partly working for companies during their PhDs, and Thomas works on developing sustainable fuels.  My research background is yeast genetics, which is quite different to that of my team members!  However, one of the best aspects about ACTION is that inter-disciplinary collaboration is encouraged and we soon found that we had a number of similar business ideas.

The initial two-day residential meeting for ACTION2013 was held during a cold snap in March, so we started looking at a socio-economic measure called fuel poverty, which is where households spend 10% or more of their income on heating their homes adequately. We did a little more research and found that nearly 25% of households in the North East are in fuel poverty – the second highest rate in England.  We decided to build a social enterprise around reducing fuel poverty, and believed that the best way to do this would be to offer cheap home insulation that was suitable for any home.  The North East has very old housing stock, most of which does not have cavity walls, so we wanted to develop internal insulation for solid walls.  Also, we wanted our product to be sustainable so we experimented with using finely shredded household plastic as the insulation material – currently only around 50% of household plastic waste is recycled.  At this point we decided on our name, ThermoLastics – Thermo for warmth, and Lastics for making plastics last for longer!

Our first prototype product was a plasterboard panel filled with finely shredded plastic from household plastic waste.  The panel is fitted to the internal wall of the home.  Our second prototype used a 3D-printed plastic matrix that can be filled with shredded plastic insulation.  Currently, we are investigating ways to maximize the insulation potential of plastic waste, such as using finely milled plastic to form fibres.  To find out more, visit http://www.thermolastics.co.uk/

Overall, we hoped that our business would address all three of the societal challenges: sustainability (through using recycled plastic), social renewal (by reducing expenditure on fuel bills, which might help families to lead more active, social lives) and changing age (because 50% of those in fuel poverty are over 60).

The Thermolastics team, Amy Green, Thomas Bohl, Eesha Raut and Kate Clark being presented with their award by Dr Bryn Jones, the Newcastle University Dean of Postgraduate Studies

ACTION 2013 culminated in a one-day showcase event at the Great North Museum, which was part of the British Science Festival 2013.  Teams first pitched their ideas to a panel of judges, who were business experts from the North East.  Then, teams opened their trade stands, displaying their business ideas, to judges and the public. We were delighted to be declared the ACTION 2013 winners, as decided by the expert judges, and were thrilled to be awarded the People’s Choice Award too – decided by votes from members of the public.  The prize awarded by the judges is £2,000 per team member to put towards developing the business further, or developing ourselves as entrepreneurs.

Prior to ACTION 2013, I had no business experience but by the end of the programme, I had helped design and develop a product, produce a business plan, pitch the business and run a trade stand – so I have learned a great deal.  The ThermoLastics team has decided to stay together and explore ways in which we can fund research and development for our product.  Perhaps we will even bring it to market in the future – watch this space!

 

Links

Action 2013: http://research.ncl.ac.uk/action2013/
Thermolastics: http://www.thermolastics.co.uk/
The Lydall Lab: http://research.ncl.ac.uk/lydallab/Welcome.html
Newcastle University Societal Challenges: http://www.ncl.ac.uk/about/values/societal/
British Science Festival 2013: http://www.britishscienceassociation.org/british-science-festival