Author Archives: administrator

Committee News

We look forward to meeting BSCB members at the Spring Meeting AGM.

  • Woods Scawen Lecture Theatre, University of Warwick; 18:00-19:30

We would like to warmly welcome our new postgraduate rep, Clare Mills who is based in the Institute of Opthamology at UCL in London and say thanks and farewell to the outgoing rep Kimberly Bryon-Dodd who gained her PhD recently and is off to pastures new. We also have elected four new committee members recently: Prof. Nancy Papalopulu from the University of Manchester; Prof. Ana Pombo from Imperial College, London; Dr. Silke Robatzek from the Sainsbury Laboratory, Norwich and Dr. James Wakefield from the University of Exeter. You can find out more details on the Committee page.

Career story: Gravesend to Glasgow (UK), via USA, ‘on a braintrain’

[Adapted from: ‘People and Ideas’, Journal of Cell Biology, and produced with the kind permission of Professor Karen Vousden, Director, Beatson Institute for Cancer Research, Glasgow]

If at age 14 you told a Careers Adviser visiting your school that you wanted to be a Research Scientist and they said “that’s much too difficult, how about working in a bank”. What would you do?

Professor Karen Vousden, now Director of the Beatson Institute for Cancer Research, Glasgow, UK, had other ideas.

When Karen Vousden was a little girl growing up in Gravesend, Kent, UK on the South bank of the River Thames she wanted to be a teacher. Her mother was a school dinner lady and her father was a skilled toolmaker in a local factory. Karen’s mum and dad supported Karen in her school work, but neither of them knew much about careers in science.

After primary school Karen went to Gravesend Grammar School for girls and it was here, Karen says, that she had outstanding chemistry and biology teachers. She became absolutely fascinated with these science subjects and her teachers encouraged Karen to follow her ambition of becoming a scientist (and not to follow the careers advice). After secondary school Karen went to Queen Mary College, University of London. Here she followed a course in general biology but graduated with a BSc in microbiology and genetics in 1978. She followed this, at Queen Mary College with a PhD in genetics in 1982.

Karen has always said that she did not have a career plan or strategy but made her career decisions, given her interests and qualifications, on what she thought would be interesting and enjoyable work. Towards the end of studying for a PhD Karen thought she had better think about getting a job!

A post (advertised in ‘Nature’, a weekly science journal) at the Institute of Cancer Research in London attracted Karen’s eye. She obtained this post-doctoral appointment and stayed there from 1981 to 1985. She enjoyed the exciting and intense research environment speaking of it as “fantastic” right from the start.

Karen’s next move was to go to the United States “because she thought it would be fun to work there”. At the National Cancer Institute in Bethesda she worked on Human Papillomavirus, a virus associated with cervical cancer and for which there is now a preventive vaccine.

After Bethesda Dr Vousden returned to London to set up and lead the Human Papillomvirus Group at the Ludwig Institute for Cancer Research from 1987 to 1995 after which she returned to work in the USA. In America Karen held several posts directing laboratories and programmes during which time became interested in the functioning of a gene called p53, other genes associated with it and the protein products of them. In 2002, Professor Karen Vousden was appointed Director of the Beatson Institute for Cancer Research in Glasgow, UK, where she has overseen a £15 million expansion plan. In addition to directing the Beatson Institute, Professor Vousden leads her Tumour Suppression research group where her team to work on the p53 tumour suppressor gene. Professor Vousden is a Fellow of the Royal Society and the Royal Society of Edinburgh and has received many honours for her work including a CBE.

Biological aspects of Professor Vousden’s work
If you are studying biology at school the chances are that you will not have heard about the p53 gene, but if you are a teenage girl in the UK you will probably have been offered a ‘jab’ to protect against human papillomavirus (HPV).

The p53 gene and the protein products associated with it, that Karen and her team now work on, have a pivotal role in cancer. This is because ‘p53’ is a so called ‘tumour suppressor gene’. It has been called the ‘guardian of the genome’ because during the G1 phase of the cell cycle, (which you will study in general outline), p53 acts as a quality control checker. It only allows cell division to continue if the quality of the genetic material in the nucleus is acceptable. If the quality is not good the p53 gene induces the cell to commit ‘cell suicide’ [called programmed cell death or apoptosis]. In most cancers it has been found that the p53 gene is either absent, damaged or malfunctioning. It now appears from Professor Vousden’s current work that p53 may have another role to play. [Ref: Yee, K. S. and Vousden, K H., (in the journal) Carcinogenesis vol.26 no8 pp1317-1322, 2005]. You could have a part to play in this research. Join us in the cell biology community!

Take Away message:
Professor Vousden has said that she based her career decisions on whether the work would be interesting and enjoyable, but she says, success only comes with hard work and, because there are disappointments along the way, you really need to choose an area of work that you can feel passionate about and enjoy.

Link Out:
See for more information about the Beatson Institute for Cancer Research. For more information about programmed cell death, p53 and the cell cycle at At the home page site select softCELL e-learning, then ‘Key Concepts and Messages, No.9 Cell Cycle Control’


BSCB Science Writing Prize 2013

Our own worst enemies? Why resistance is not futile, and what that means for cancer research

Sarah Byrne, Imperial College London

When the new millennium dawned, it felt like the future was finally here.

“Is this the breakthrough we’ve been waiting for?” the May 2001 cover of TIME magazine asked. Gleevec pills, golden and bullet-shaped, shone bright against a dark background. The imagery was clear: was this the magic bullet that would cure cancer once and for all?

“I think there is no question that the war on cancer is winnable,” said the director of the Memorial Sloan-Kettering Cancer Center, quoted in the same article.

Gleevec was a new drug to treat chronic myeloid leukaemia (CML), a fatal blood cancer affecting hundreds of people per year in the UK and several thousand in the US. It was also the first of a new generation of ‘targeted therapies’, smart drugs that would precisely target cancer cells. These were to be more effective than traditional chemotherapy, especially for hard-to-treat cancers such as CML, and with fewer side-effects as well.

But problems started to appear. Some patients who were initially responding well started to relapse: their cancer was developing resistance to the new drug. In the following years, several alternatives to Gleevec were developed to treat the drug-resistant cases. And again they initially seemed to work, but eventually the same problem arose. A decade later, that problem remains unsolved.

Resistance has in fact plagued most attempts to develop targeted therapies for cancer. It seems to be an inherent problem of the approach: its greatest strength — the precision targeting of a single gene or protein — is also its weakness. Only a small change or mutation in the cancer cell is necessary to stop it working.

But hasn’t all this happened before? The same rhetoric — ‘magic bullet’, ‘miracle drug’ — heralded the arrival of penicillin. And look at how that turned out.

Resistance is now a well-known problem in bacterial infections. These include the infamous MRSA ‘superbug’ which can now evade most commonly-used antibiotics; including, of course, penicillins. It’s a similar story with viral infections, including HIV: resistance is an increasing concern. Resistance to anti-fungal pesticides is a major issue for agriculture.

It’s not just the tiny things, either. When the disease mxyomatosis was introduced to control the rabbit population in Australia and Europe, it ended up producing a resistant population (‘superbunnies’, maybe?) and numbers began to increase again. It isn’t even strictly limited to living things. Resistance has been observed in prions — the abnormal protein molecules involved in neurological diseases BSE and CJD — which few would define as ‘alive’, though perhaps that definition is becoming less certain.

We do know that resistance is universal; inescapable. Whenever you apply a selective pressure to a population — anything that kills or impairs a large proportion of that population — you favour the survival of those who can resist it. Before long, they become the population.

Cancer cells are no different. They want to survive, to live as long as possible: forever, if they can. They want to be individuals, do their own thing, spread and migrate and colonise, build infrastructure to support themselves; heedless of the damage they cause to the body as a whole. Blind to the fact that they might be killing the host that supports them.

Wait, does that sound familiar?

We often refer to cancer cells as ‘abnormal’, because of the changes in their characteristics and behaviour compared to ‘normal’ healthy body cells. But think of the ancestry of a cell. Once, in a world long before we or any complex animals existed, unicellular organisms — tiny beings each consisting of a single cell — were the norm.

Their descendants are the ‘normal’ cells that make up our bodies. But they’re different now. Obedient and well-behaved; staying quietly in their assigned place in the body. Not taking more resources than are allotted to them. Following orders even to the point of sacrificing themselves willingly for the greater good: the needs of the many outweigh the needs of the few.

Not many of us would relish the chance to live in a society like that. It seems to go against every natural instinct. We want the freedom to travel where we will, to have as many or as few children as we choose, to consume what we want: survive and thrive and pass on our genes. Even if it harms the biosphere that supports us all. That’s our nature, the same as most living things.

So when you think about it, which cells are really the abnormal ones?

And right here is the problem we have come up against. If we didn’t have that drive to live and survive, we probably wouldn’t be trying to cure cancer in the first place. But we can’t have it both ways. If we are to have the imperative to survive, so must other forms of life — our common evolutionary history makes sure of that — and sometimes their needs come in conflict with our own. Usually, of course, we win. But when the conflict comes from within our own bodies, from our own oppressed cells turning freedom-fighter against us? The irony is particularly cruel, and particularly difficult to overcome.

None of this should detract from the advances that have been made. Gleevec was essentially a success story, as was penicillin in its time. For all the problems, Gleevec and its successors have dramatically improved the life expectancy of people living with CML, a report released in December 2012 showed .  Every extra year a patient gets to spend with their loved ones, to live their lives as they choose, must count as a win.

But the recurring resistance problem highlights a paradox at the heart of medicine: the strong instinctive compulsion to survive that keeps us fighting disease and death, may ultimately be the same force that keeps us from succeeding. At times, we are quite literally our own worst enemies.

The Abercrombie Conference Fund

Michael Abercrombie was a pioneer in the study of cell migration (“Michael Abercrombie: the pioneer ethologist of cells” Trends in Cell Biol. 8; 124-126) and following his death in 1979 a conference fund was established to support a quinquennial symposium.

In 2009 the fund was incorporated into the BSCB. Grants are now available to be used by organisers of conferences in the cell motility field if they can justify a need for additional support for an invited speaker or event beyond the normal sources of conference income generation.

Applications should be made by writing a letter to one of the trustees of the fund: Gareth Jones, Michelle Peckham, Peter Clark and Anne Ridley. Please allow at least 3 months before the funds are required.

The letter should provide details of the speaker or event to be supported, the research conference concerned, a justification of the sum requested and a statement on how the application fits in with the aims of the Abercrombie Fund.

BSCB Science Writing Prize 2012

The Logistics of Cellular Traffic

David Gershlick, University of Leeds

In every cell proteins are continuously crafted and assimilated into the cells of intricate organisms. After synthesis the proteins get directed by a complex concert of cellular machinery in order to assume their appropriate role. The eukaryotic cell can be roughly divided into several different sub-sections. Surrounded by a liquid membrane, analogous to the rubber of a balloon, cells contain a watery molecular soup, which is further accompanied by membranous sub-compartments (referred to as organelles). These organelles form specialised environments with distinct roles and characteristics. Proteins fulfil functions within the membranes, at the membrane periphery or in the liquid throughout the cell. Organising these processes is a multifaceted task with numerous components needing to deliver particular proteins to specific destinations.

Scientists choosing the task of unravelling these phenomena had a complex assignment. Early techniques allowed cells to be sliced into thin sections and imaged or split open and separated. It was the 1974 Nobel laureate George Palade who coupled the observed structures with particular functions. Palade, faced with an unnerving array of cross sections of cells, wanted to understand how proteins leave the cell. The approach involved adding a radioactive element, which was incorporated into freshly made proteins, then checking where the radioactive proteins were at different time points. Essentially, the route a protein took through the cell was tracked. These observations set the stage for the introduction of the secretory pathway as a functional system of organelles.

In the following years many conceptual breakthroughs were made. One such event was the isolation and characterisation of the ‘coated vesicle’. Vesicles are small spherical compartments shuttling from one organelle to another. Filled with proteins and other components they provide a mechanism for the transport of proteins, without having to cross a membrane. Vesicle budding/fusion events were characterised by in vitro reconstitution from isolated organelles. The rate at which these vesicles bud, migrate and fuse is unexpectedly high. It was once calculated that in mammalian cells there are approximately 155 of one particular type of vesicle budding per second. Cells are alive with hundreds of independent vesicles, sometimes travelling the length of the cell to specifically deliver their valuable contents.

In the late seventies researchers realised that there was a plethora of functional proteins waiting to be discovered. Yeast was the perfect organism for this work. They are single cells, with genomes simpler than mammalian or plant, but a seemingly as complex cellular architecture. Yeast geneticists led the way over the following 20 years with several key studies all with a shared principle. The genomes of whole populations of yeast were randomly mutated and screened to look for protein sorting defects, and the responsible mutation isolated. Although there was a degree of overlap in the studies, often new essential proteins were discovered. These methods identified a large array of effectors, allowing the mechanisms of specific processes to be elucidated.

It was understood that if a protein needs to reach a particular cellular destination to fulfil its role then it cannot do so passively. They need to be directed somehow to fill the place reserved for them in the relevant vesicle or compartment. Thus, to differentiate proteins from one another, they have specific signals. This led to the distinction of ‘cargo’ that is transported, from ‘receptors’ that mediate transport steps. In a further layer of complexity, these receptors must continuously recycle to pick up another round of cargo, much like a postman returning to pick up more letters to deliver. Often receptors pass through multiple compartments to deliver cargo. These mechanisms and protein interactions occupy scientists (including myself) to this day.

With the discovery of fluorescent proteins the study of protein trafficking had a technical revolution. Fluorescent proteins light up in a distinctive manner, in a background of effectively invisible peers. Making fused chimeras consisting of a protein of interest attached to a fluorescent protein has become commonplace. Fluorescent microscopy allows observation of the location of a protein within the context of a three-dimensional cellular environment avoiding having to slice the cell into sections. Impressive recent advances allow single molecules to be observed, as well as the imaging of vesicles in living cells.

By complementing technical developments with scientific progress the conserved mechanisms that marshal a very complex system are being exposed. Associated with defects of the pathways there are various human disorders, where understanding membrane trafficking holds hope for effective therapies. A range of microorganisms are known to hijack these pathways obtaining access to the protected inner cell, a better understanding of these perturbations not only sheds light on the processes mediating homeostasis in healthy cells but would also drive medical innovations. In my field of plant biology we study these processes to not only to gain an understanding of cell biology but also to work towards global issues. Comprehending the secretory pathway allows us to progress to the goals of creating storage compartments in plant cells for industrial and pharmaceutical proteins, to generate extra-nutritious food and even to produce biofuel in a more sustainable and yet profitable manner.

The revolutionary breakthroughs described in this article seem to have occurred every 5-10 years, and perhaps it would be prudent to anticipate another such progression. However, I believe, such predictions are misplaced. Science funding seems to have changed impetus from the so called ‘blue-sky’ research to an applied focus. Each of the advances discussed above are a direct result of curiosity driven blue-sky work, as any major novel innovations would also likely be.  That is not to say that applied research is not valuable, but with the majority of researchers having to focus on foreseeable impact in order to justify funding, it would seem obvious that the likelihood of major unexpected breakthroughs decreases. However, if the historical advances have taught us anything, it is that progress can happen in unexpected places at unexpected times and it is an exciting time to observe the subtle mysteries of the cell being gradually disentangled.

BSCB Science Writing Prize 2011

What makes us tick?

John Ankers, University of Liverpool

From the changing seasons to our daily sleeping patterns or the beating of our hearts, biological cycles are all around us. What we now know is that some of these very different natural cycles work together like cogs or gears in a giant clock. Understanding how these clocks work (and how they can go wrong) might bring new hope for treating diseases such as cancer.

In the northern hemisphere, the passage of the Earth around the sun gives us cold winters and warm summers. These, together with daily tidal patterns controlled by the moon’s orbit and a day-to-night cycle driven by a constantly spinning planet, put considerable strain on life on earth. How have plants and animals adapted to deal with such dramatic changes?

Imagine a huge, but invisible, clock. Environmental changes brought about by the sun and the moon turn cogs in this clock. The seasonal cog moves around once per year, the day-to-night cog is smaller and turns every 24 hours. These cogs are linked: as the earth moves around the sun, not only do the seasons change but the days get longer or shorter. Plants and animals have their own invisible clockwork. Each turn of the Earth’s light/dark cycle creates “circadian” (Latin meaning “about a day”) patterns of daily growth in plants and sleep in humans. The mechanics of the circadian cycle are complex, having evolved over millions of years, and sensitive to unexpected changes in the environment. This allows, for example, humans to react to abnormal periods of light or darkness (which may be experienced as jet lag) or plants to change their metabolism to compensate for a particularly harsh winter.

Many of the cells in the human body are repaired or replaced continuously (skin cells replace roughly every day, whereas nerve cells are never replicated). Fortunately for our clocks, this “cell cycle” is governed by a number of failsafes, ensuring that the correct cells are replicated in the correct way, and that this doesn’t happen too slowly – leading to problems in early development, or too quickly – leading to the possibility of tumour formation. There has been much work done (and a Nobel prize awarded) on the discovery of proteins that regulate the pace of cell division. The cell cycle is mechanically connected to our daily circadian cycle (their cogs are linked), suggesting that the human body might be able to renew itself more efficiently at different times of the day or night. Recently, the cell cycle has been shown to interact with an intriguing group of different cogs. These much smaller, faster cogs (cycling from 100 minutes up to 6 hours) can be “hooked up” to the clockwork when they receive emergency signals – such as the need to respond to an infection, or if DNA inside the cell is damaged – freezing the cell cycle of a faulty cell before it can be replicated so that threats may be averted or any damage repaired.

All of this makes our clock incredibly complex. Nevertheless, many of these cogs are turning now, in every cell in your body. Some are accelerating, stopping and restarting whilst some are checking, repairing, destroying and rebuilding, and it is the links between these cogs that have dramatic effects on the overall clockwork, and hence the health of our cells and tissues. So what happens to the clock in diseases like Alzheimer’s or cancer? And how do we, as observers, even contemplate fixing a faulty clock?

One of the reasons cancer is so difficult to treat is that a faulty cog in our clock (such as a cell cycle that is cycling too quickly) may be joined to many other “healthy” cogs such as those driving DNA replication and repair or the response to infection. Chemotherapeutic agents are used to destroy cells in the body with faulty cell cycles, but by doing so may also interfere with some other healthy cogs leading to severe side effects. Think of the challenge in repairing one faulty cog in the workings of a grandfather clock without disturbing the rest. Now imagine doing that whilst all the cogs are moving!

But it isn’t all bad news. Such a complex problem is being tackled in new and fairly unorthodox ways. My field, that of “Systems Biology”, is devoted to reconstructing the mechanisms that beat, pulse and oscillate inside the human body as computer models, just as an engineer might build a computer model of a plane or a skyscraper to identify and correct problems in its design. These models allow us to “virtually” unpick the clockwork of the human cell to see what makes it tick, and then probe and prod various parts in a way that might be too costly in the laboratory or unfeasible during surgery.

As we begin to understand more about how the clockwork of the cell is connected – how large, slow cogs wheels such as changing seasons, the circadian clock or cell cycle turn with smaller cogs like those driving emergency responses (or even smaller cogs cycling every few seconds like those driving electrical pulses in the heart or nervous system) – we may be able to design combination treatments that exploit the links between them. Slowing the cell cycle temporarily, for example, might allow a second drug to prompt a response to infection, which would otherwise have been blocked. Although there is still much to learn about our internal clockwork – exactly how connected are all of these different cogs? Are there any we have yet to discover? – the ability to help a diseased cell to repair (or re-set) itself no doubt offers an exciting prospect, and is surely only a matter of time.

BSCB Science Writing Prize 2010

Inducing Apoptosis- Countdown to Self-Destruction

By Susan Turrell, University of Leeds

From very early on in its life, a human cell is destined towards a particular fate. This job could be conducting electrical signals along a neural circuit, travelling through the body’s system of blood vessels on the lookout for harmful pathogens, or sensing light that has been focussed onto the retina of the eye, allowing us to visualise the world around us. But what happens if this pre-established plan goes wrong? What if this cell becomes infected with a malicious micro-organism, or if a vital signalling pathway becomes erratic and unstable?

Like an ageing car, if the cell is too damaged or dangerous to mend, it’s seen as a write-off and needs to be scrapped. Fortunately, every cell in our bodies has instructions for a self-destruct program maintained within its DNA.  If it can’t be mended, events are set in motion that culminate in the termination of that cell. This process is called apoptosis.

Apoptosis is a neat and precise method of eradicating cells in a multicellular organism. It involves the systematic shutdown of the cell, and occurs in an ordered sequence. First, the material in the nucleus, called chromatin, condenses and the cell shrinks and contracts. Second, the nucleus disintegrates and the structures inside the cell fragment. Finally, small enveloped pieces of the cell break off in a process called blebbing. The cell has essentially been packaged up into parcels called ‘apoptotic bodies’ for immune cells to engulf and dispose of.

However, apoptosis is not just a method of ‘clearing up’ damaged cells. The cells in our bodies are multiplying and dividing all the time, and yet we don’t just keep on getting bigger and bigger. Programmed cell death balances out this growth so that the number of cells in our bodies stays relatively constant. Apoptosis is also a fundamental part of development in the foetus. It is essential for sculpting individual digits by removing the webbed tissue between our fingers and toes. It’s also important in the developing nervous system. When they’re growing, several nerve cells all strive to form a connection to a corresponding nerve or muscle cell. Those that make contact can transmit electrical impulses to stimulate movement or sensation, while those that fail to reach are eliminated.

So what’s the mechanism behind this process? This countdown to controlled self-destruction is triggered in two ways. The cell can receive an external signal from other cells, or the process can be kick-started from within.  For example, receptors on the cell surface await a signal from immune cells which are like sentries, patrolling for potentially dangerous fugitives lurking inside cells. When they recognise that a cell is harbouring pathogens such as viruses or bacteria, the immune cells release factors which cause the infected cell to commence its ‘suicide program’. As well as this system, sensors inside the cell such as the protein p53 act as wardens for irreparable cell damage. p53 effectively performs an M.O.T on the cell by inspecting the DNA contained in nucleus. Depending on the level of any damage found, it either directs the repair of the affected DNA strand, or activates the self-destruct program. It does this so that any damaged DNA is not copied and passed on when the cell divides. Once these cell sensors are activated they start a cascade that amplifies the ‘death signal’ so that it cannot be switched off. The signal gets passed along to different proteins like a baton in a relay race, but each protein has several batons and so each handover involves more and more runners. In this way the cell becomes committed to the death program and can’t recover.

The final runners in this relay are a group of proteins called caspases. Caspases are expressed as inactive enzymes and have evolved to chop up other proteins when they get switched on. The termination signal is passed from ‘initiator’ caspases down to ‘executioner’ caspases, which are the bulldozers of apoptosis. These enzymes set about dismantling the structural components of the cell and this deconstruction leads to the breakdown of the cell contents.

When apoptosis stops working it can have disastrous results. One consequence is the uncontrolled growth of cells, leading to cancer. Cancer is caused by multiple mutations in different types of genes, and one of the most common proteins affected is the guardian of the genome, p53. If defective, this protein can’t activate apoptosis, and therefore cells that already have damaged and mutated DNA are allowed to multiply. Lots of cancer cells also have mutations in proteins involved in the apoptotic signalling cascade, so they can grow even when the cell is instructed to commit suicide.

I’m currently developing a gene therapy vector to treat cancer. This involves transporting a gene for a protein called TRAIL into cancer cells. TRAIL recognises cells that are carcinogenic and binds to cell surface death receptors. This activates the apoptotic signalling cascade from the outside.  If successful, this therapy would be specific to cancer cells, so would have fewer side effects than conventional cancer therapies. However, as some cancers have damaged apoptotic pathways, this treatment won’t be useful for all cancer types. I like the idea behind this potential therapy because we are using the body’s own defence system to kill the cancerous cells, we just give it a little extra ammunition.

Apoptosis is one of the mechanisms that maintains the balance between growth and stasis, health and disease. This balancing act is vital, as a problem in a tiny element of this pathway can have a massive detrimental effect. The body has evolved a way to sacrifice defective parts for the benefit of the whole organism. For this reason, each individual cell holds the seed to its own destruction.