The problems start when they try to scale the academic ladder. There are too many scientists at this stage of their career competing for too few permanent academic posts, so competition is tough, which can be demoralising. Worse, postdocs can find themselves trapped in a cycle of temporary contracts, with senior academics reluctant to promote them over younger colleagues. And if they try to get a job of equivalent seniority outside science, their extensive lab experience may count for nothing.

The good news is that life for postdocs is improving as the British government pumps more money into developing the careers of research staff (see “Cash injection”). Whether you are planning a postdoc or are thinking about moving on to the next stage in your academic career, however, you will greatly improve your chances of winning a permanent post by honing a few basic skills and employing some simple tricks.

Before you go any further, be realistic about your chances of securing an academic position by comparing your abilities with those of your peers and by asking for honest feedback about your work and potential. Taking this attitude to your career from the start can make all the difference, says Sara Williams of . “One of the big things a researcher can do to help themselves is to plan, and to approach their career with the same rigour that they would use in their research,” she says.

Whatever position you are applying for, your research abilities will be key. “The most important thing is your credentials as a scientist and as an academic, so obviously your publications list is crucial,” says Liz Willcocks, a careers adviser for physical science postdocs at the University of Cambridge. Where possible, you should push for first authorships (scientists who do most of the research and management) and last authorships (usually the most senior people working on the project). Either will demonstrate your ability to manage projects and think independently, says Matthew Wakelin, senior research manager in personal awards and training at Cancer Research UK.

Taking on responsibility also proves you can work independently, even if it is just managing an undergraduate’s research project. As does moving between institutes, says Wakelin. “If somebody has stayed in the same location, one of the big difficulties is knowing whether they can actually break away from their supervisor and establish themselves as an independent person,” he says.

Demonstrating that you have the initiative to come up with proposals for new research programmes will also play a pivotal role in the assessment process for an academic post, so it is worth spending time on these, bouncing ideas off colleagues and even asking senior researchers for advice before submitting ideas. “Regardless of whether you have previously led 10 Nature papers, you’re not going to get funded if you have the worst proposal ever,” he says. When developing a proposal, it is important to be honest with yourself about the hurdles you are likely to face and how you could overcome them. Don’t be overambitious.

Research aside, there are several other areas postdocs can focus on to make themselves more attractive for academic posts. One is the ability to raise money for research projects. Obviously winning a fellowship early on is the best evidence of this, but for postdocs who don’t have this experience, any demonstration that you can secure money for your research will make you a more exciting prospect for cash-strapped departments.

“There’s no point in having all the ideas in the world if nobody will fund you,” says John Bothwell of the Marine Biological Association in Plymouth and founder of the . “But there are plenty of small grants for which people can apply for trips to other labs, or trips abroad, or to workshops. Just the experience of sitting down and practising writing applications for money was the single most important factor, I think, in getting my fellowship.”

Another good tactic is to market yourself, which means building up a network of people you know in the field. “Academics tend to be very modest and humble as a species, but pushing themselves forward is key, not being afraid to show what they’ve done and producing the evidence for that,” says Williams. “That’s how recruitment works.” You should aim to get yourself and your work known by presenting in public, particularly to people you would like to work with one day.

“Academics tend to be very modest and humble as a species”

It is also worth being choosy about the postdoc positions you take on. For example, finding a supervisor who is willing to invest in your future can help your career enormously, and larger departments may provide more opportunities for you to move up than smaller ones.

So if you apply all your skills, are proactive and grasp every opportunity that comes your way, you will give yourself the best possible chance of securing a permanent academic position – though not before enjoying the best years of your career first.

What’s more, researchers find great motivation in the distinct possibility of developing powerful treatments that save lives. “The fact is that around one in three people will still get cancer,” says Steve Jackson, a laboratory head for Cancer Research UK and professor of biology at the University of Cambridge. “There are very few people who aren’t touched by cancer in one way or another, and to know that you’re working in an area that has the potential to make the lives of so many people better is a big positive.”

In recent years, the field’s popularity has contributed to careers in UK cancer research becoming more competitive for scientists, who now need something more than a passing interest in cancer to make any waves. “Because of its high profile and because it’s such an exciting area of science, it’s a highly competitive and dynamic place – you have to keep your wits about you,” says Jackson. To succeed, it’s vital to keep track of how cancer research is evolving and ensure you nurture the right skills to adapt. żěè¶ĚĘÓƵ asked a selection of leading cancer researchers – from scientists near the front line of hospital treatment to Nobel prizewinners – what it takes to excel in the field today (also see “Leading lights show how to shine”).

One of the most significant trends cancer researchers should be aware of is the increasing emphasis on “translational” research. In essence, this is about fast-tracking discoveries from the lab bench to the patient’s bedside as quickly as possible. For example, the UK’s largest cancer charity, Cancer Research UK, recently joined forces with the various departments of health across the UK in a £35 million project to form a network of Experimental Cancer Medicine Centres over the next five years. At 19 new cancer centres, people from various backgrounds – including academia, charity, industry and hospitals – will collaborate to develop new drugs and treatments.

All this focus on translational research means big changes for the scientists involved. Patients now take centre stage, and research must be viewed in terms of how it could eventually be applied to help them. For basic researchers, this means having at least some awareness of the clinical and public health issues affecting their work.

Clinical mindset

Charlie Swanton, a clinician scientist at the Cancer Research UK London Research Institute, says his clinical experience has helped in directing his academic work. “Very often in science you come to a fork in the road and you’re not sure which route to take. Sometimes having a clinical perspective helps you prioritise laboratory problems,” he says. Swanton and his colleagues are hunting for genes that cause patients’ cancers to become resistant to a class of drugs called taxanes. So far they have found a series of genes that appear to be linked to this resistance. Even more intriguing is that these same genes induce polyploidy – having more than two copies of each chromosome per cell – in tumours. This fact could be useful for doctors, because spotting polyploidy in patients’ cells could help them pinpoint which individuals could be resistant to the drugs, as well as who might respond most effectively. Without his clinical experience, Swanton might not have spotted this potential to apply the research findings, he says. A traditional biochemist might have chosen to look closer at the functions of one or two of the genes instead, for example.

Translational research also requires scientists to work closely with each other, so it’s important to know how your work can influence other disciplines, says Simon Vincent, head of personal awards and training at Cancer Research UK. “We don’t expect everybody to suddenly start designing drugs. If you’re a Drosophila [fruit fly] geneticist, fantastic – be an excellent Drosophila geneticist. All we ask is that you think about where you fit into the bigger picture. Think about the data and information and results that you’re generating, and whether you can pass that information on to the next stage, and who you can collaborate with.”

A willingness to learn about other disciplines can be a real advantage in your career, says David Knowles, chief scientific officer at Berkshire-based Piramed Pharma, a biotechnology company that develops cancer drugs. “Cancer research is very complex, bringing a whole set of different experiences and thoughts together, and it’s the people who sit at the boundaries who can help make or break a company,” he says.

A wider perspective could prove particularly useful now that many pharmaceutical companies are conducting their own basic research as well as concentrating on molecule discovery. Encouragingly, companies and universities are increasingly working together, says Andrew Hughes, medical director in oncology and infection drug discovery at AstraZeneca. “Clearly each of those parties has a potentially separate agenda. But we all have a common goal, which is that we want the drugs to get to patients.”

“We all have a common goal: we want the drugs to get to patients”

Charities and hospitals are also seeing the benefits of pooling their resources. Take a look at the new Manchester Cancer Research Centre, where the Paterson Institute for Cancer Research has joined forces with the nearby Christie Hospital Foundation Trust, the University Of Manchester and Cancer Research UK. “It’s really working,” says the centre’s director Nic Jones. “The centre has only been going for a year and a half, but we’ve made a lot of advances in terms of building up our research infrastructure and developing new areas of research that wouldn’t have happened if we hadn’t got together.”

Manchester is not alone, says Vincent. Many other universities and medical schools are specialising in cancer. Such up-and-coming hubs of activity can provide new job opportunities for cancer researchers and could be good places to make your mark, so try to keep track of what’s new.

Of course, succeeding as a cancer researcher is about much more than spotting the fashions in your field. Swanton believes that your work should almost be your hobby. “If you’re going to be in this field, there’s not much time for reading normal books: when you’re at home, you tend to read papers, PubMed [the medical search engine] or analyse your data, because that’s the only way you can keep up with both lab and clinical commitments,” he says.

The real key to success in the cancer-research industry is having the resilience to keep going even when the work gets tough. “You need to put the hours in,” says Tim Crook, team leader for the cancer genetics and epigenetics laboratory at the Breakthrough Breast Cancer Research Centre in London. “It all comes down to passion, motivation and a desire to be the best. I know it sounds very old-fashioned, but that’s what makes the difference between the winners and the losers in science.”

So despite cancer’s complexities, and the wider changes in the field, if scientists can stay on top of the information and refine their skills to fit the ever-changing research environment, there are real opportunities for success in what is still a hugely exciting and rewarding area. “Once you get into the field and start defining what it is you want to work on, some of the complexity melts away,” says Jackson. “In the end, what really matters is that you’re a scientist: you’ve got to come up with a hypothesis and test it.”

This instability in the business, and therefore in jobs, can be a risk for scientists. “It matters a lot if you pick the wrong company and it goes bust. You find yourself back in the job market with only a PhD and a track record with a failed company,” says William Powlett-Smith, a biotech analyst at Ernst & Young.

“It matters if you pick the wrong company and it goes bust”

It is impossible to know for sure which companies will survive and thrive, but you can spot the clues without delving into financial facts and figures. Dig beneath the surface and you can uncover essential information about the company’s culture and perks.

When job-hunting in biotech, the first thing to look at is the science, says Stephen Jackson, who founded Kudos Pharmaceuticals, a UK biotech company developing cancer drugs. It may seem obvious, but only good science will succeed commercially. “You can go into a car showroom and know some cars are better quality than others just by looking at them. In the same way, if you’re a scientist in the appropriate field you will normally have a very quick response as to whether something is good or not – it’s instinctive,” he says.

Unfortunately, good-quality science can still fail if the people steering the company take a wrong turn, so also try to check up on your future bosses. Powlett-Smith says the key trait to look for in managers is experience, because those who have learned from both the successes and setbacks in such an unpredictable industry are likely to do the best job. Good management teams also tend to build links with other companies and academic institutions abroad. After all, drugs are needed all over the world, so these links provide access to new markets and bring in top-flight expertise.

If the business has been acquired by a much larger one, such as a big pharmaceutical company, chances are the new bosses will have that international outlook and experience. The bad news is that ownership by a bigger fish can sometimes mean that your job is less secure because the company may eventually be broken up or moved. There is a third way, however. Kudos is now owned by AstraZeneca, for example, but has been left to run itself and no scientists have lost their jobs. According to Jackson, companies like Kudos that are established in their own right tend to survive intact, whereas younger firms with fewer staff, which rely on only one or two drug compounds for their business, can be more vulnerable. “If a company has just one thing – a product – then you can imagine that’s very moveable,” he says, “but if a company has got expertise in discovering and developing drugs or medical devices then why would you want to break up a winning team?”

Location, location

A company’s location can also influence its prospects, says Powlett-Smith. Companies in science parks might have an advantage, particularly if they are young, as scientists can easily network with their peers and forge business relationships with other companies and investors. “Being part of a cluster, working in properly designed buildings rather than knocking around in academic buildings, and coming from a place people have heard of can all help you get through potential investors’ doors in the first place,” says Jackson. And of course, being in a cluster can be good for your career progression, by placing you in the midst of potential employers. Today you are no longer limited to the south-east of England if you want to work in these clusters: the north-west and Scotland both have growing networks of biotech companies.

Even if you find a well-placed biotech employer that looks set for success, your background checks shouldn’t end there. Given the diversity in the industry, it is important to choose a company with the right culture for you. For instance, smaller companies are likely to have a more pronounced “family feel” (see “Extras, extras!”).

To find out about the company culture, try to meet as many people working there as possible. “It doesn’t take much – you can pick it up subliminally,” says Keith McCullagh, president and CEO of Santaris Pharma, which develops cancer drugs. “If you go along to an interview and you talk to people you can tell whether they enjoy their work or not, and if it’s a fun place to work.”

Day-to-day duties vary wildly between biotech firms, and they are likely to change from one week to the next. As companies grow, for example, scientists involved in conducting experiments, analysing data and writing reports could quickly move onto managing teams, helping with sales pitches, or even assisting on the financial side. If that variety appeals to you, it’s worth asking your potential employer about those opportunities. Marcus Messenger, a senior scientist at Proximagen Neuroscience, says your best bet for landing these roles is to join a company in its youth, because as it grows and new positions become available you are likely to be first in line for promotion into a position of greater responsibility.

It’s worth bearing in mind, though, that in a small company, where fewer experienced people are available to coach you, taking on new responsibilities can be a challenge. It is worth checking out what training a company will offer, says Neela Mistry, a research officer at Cancer Research Technology, the arm of charity Cancer Research UK that helps academic researchers develop cancer drugs. When Mistry joined she was sent on a course to show how she fitted into the whole project and says this benefits her work even now.

Of course, training isn’t the only perk you should look for. Financial incentives such as company share option schemes can prove lucrative if you buy into a new company which goes on to great success. “Share options can potentially make you more money than your wages, and offering them to employees means it’s in everyone’s interest for the company to succeed,” says Messenger.

As the industry goes from strength to strength, your odds of finding a successful company with the right culture and perks are better than ever. Ernst & Young, which produces annual state-of-the-industry reports, says biotech in Europe now seems to be recovering from the bursting of the genomics bubble of 2000, when share values crashed and investors lost faith in the sector. The industry as a whole is still failing to turn a profit, but there is a greater diversity of companies and many businesses are stronger than ever as their drugs come closer to market. With increasingly attractive career prospects available, you can afford to be choosy.

The treatment, which is taking place in London, UK, hopes to restore vision in patients who have a genetic defect that causes degeneration of the retina.

Robin Ali at Moorfields Eye Hospital in London and colleagues are treating adults and children with Leber’s congenital amaurosis (LCA), caused by an abnormality in the RPE65 gene. This gene is important in recycling retinol, a molecule that helps the retina detect light. People with LCA usually lose vision from infancy.

Ali’s team are inserting healthy copies of RPE65 into cells in the retina, using a viral vector. Previously, dogs with LCA have had their vision restored in this way, allowing them to walk through a maze for the first time without difficulty.

Leonard Seymour, who leads the Gene Delivery Group at the University of Oxford in the UK, and is not involved in the current trial, says the retina is a good place for gene therapy because it can be accessed by injection to overcome the problem of delivery.

“The retina is also good because it is relatively immune-privileged, meaning that the vector (in this case a virus) should not be neutralised immediately upon administration,” he says.

Important for future

The team have been developing the therapy for almost 15 years, and Ali says testing it for the first time in patients represents a huge step towards establishing gene therapy for the treatment of many different eye conditions.

“The results from this first human trial are likely to provide an important basis for many more gene therapy protocols in the future, as well as potentially leading to an effective treatment for a rare but debilitating disease,” he says.

Although some patients in the trial have already had the procedure, the researchers say it will be many months before they know whether or not the treatment has been successful.

Gregory Larkin at Stanford University in California, US, and colleagues compared the way the over 65s respond to losing and winning, compared with people aged between 19 and 27.

Participants were shown cues telling them they could either win or lose money. They had to rate their own excitement at the prospects while their brain activity was monitored using functional magnetic resonance imaging (fMRI).

The researchers found in both the self-reported tests and the fMRI scans, that younger adults showed more activity their insula and caudate – areas of the brain involved in processing emotion – when anticipating losses than the elderly. However, when winning money activity in the “emotion” area was the same regardless of age.

Benedetto de Martino at the Wellcome Trust Centre for Neuroimaging, University College London, UK, who was not involved in the study, says that experiencing reduced negative emotions could enhance well-being.

However, it could affect decision-making in older people, he says. “If older people experience less negative emotion, this means they will process losses differently.

Journal reference: Nature Neuroscience (DOI: 10.1038/nn1894)

The findings could lead to new treatments for neurodegenerative diseases in humans associated with impaired learning and memory loss, such as dementia, the researchers say.

Li-Huei Tsai at MIT in Cambridge, Massachusetts, US, and colleagues used mice that were genetically modified to produce a protein (p25) when fed an antibiotic. Previous studies have suggested that p25 is linked to brain cell death.

Before triggering p25 production, the mice were placed in a tank of water and trained to find their way to a platform submerged just below the surface. After the mice had developed a long-term memory of the task, the team induced p25 in the rodents, which led to loss of neurons, learning ability and memory.

To see if these faculties could be restored, the mice were placed in an environment enriched with toys and wheels. When the stimulated mice were retested, the researchers found they did better at the memory task than before.

Not gone but forgotten

“If memories can be recovered then that suggests they were never erased and indicates that perceived memory loss is likely to be due to an inability to retrieve memories,” Tsai says.

The mice from the enriched environment turned out to have higher levels of “synaptic marker proteins”, an indication that the “wiring” between neurons in the brain had been re-established.

Long-term gain

The next step then was to see if drug-induced histone-tail acetylations could help recover long-term memory. Tsai’s team targeted enzymes called HDACs, which prevent acetylation of histones. The researchers took mice that had lost long-term memory and injected them with a drug that inhibited HDACs. When tested, the team found that these mice were better able to find the platform in the water.

Tsai thinks that HDAC inhibitors seem to initiate rewiring of neurons. “If we could use drugs to facilitate that process I believe it would be very beneficial to people suffering from advanced stages of neurodegeneration,” she says.

Karl Giese, who studies learning and memory at Kings College London in the UK agrees that the study could have therapeutic value. “Before this we didn’t really have a handle on what we needed to do to treat dementia, so to have identified HDAC inhibitors as a drug target is very important,” he says.

Journal reference: Nature (DOI: 10.1038/nature05772)

Meerkats, famous for their cooperative behaviour, live in groups where every member has a socially defined role. But researchers have discovered a degree of insubordination in subordinate male members.

These low-status male meerkats struggle to mate with females in the group where the dominant male reigns. Now, a new study reveals they have a clever tactic to pass on their genes – they are sneaking off in the night to mate with females in other groups.

Meerkats live in groups of about 30 individuals, and the behaviour of the subordinate males has long been questioned by evolutionary biologists.

“One of the reasons people are drawn to these societies is the apparent cooperation between individuals – subordinate males don’t breed in the groups but they help to rear the dominants’ young,” says Andrew Young at the University of Cambridge in the UK. “But natural selection favours those who maximise their own reproductive success, so it seems paradoxical that these males are helping others.”

Young and colleagues monitored 15 groups of the cooperative meerkat, Suricata suricatta, on ranch land in the southern Kalahari desert. Over a five-year period, the researchers carried out genetic tests to establish the paternity of the pups born during that time.

Brief affairs

Subordinate males made regular trips to other territories during periods of peak female fertility, Young’s team observed. Previously, such forays had been explained as attempts to disperse and find a new territory where they could dominate. However, paternity testing on the pups revealed the males were in fact using these trips to mate and were doing so successfully.

Young says such extra-group mating accounts for 70% of the subordinates’ offspring, and allows the males to breed without permanently leaving their family group. Furthermore, the tactic accounts for as much as a quarter of meerkat young in the whole population.

Previous estimates of subordinate males’ breeding success have not taken into account these extra-group offspring, the researchers say.

“If the subordinates are able to get more reproductive success in other groups, then it gives them another option and may explain why they act as they do,” says Young. “The next step will be to ask why females choose to mate with these subordinate males – males can’t simply force their way into another group and mate with a female, she has to leave the group, so we need to investigate it from a female perspective.”

The most likely explanation, he says, is that such females are unable to mate within their own group – for example, they may be closely related to all the males within it.

Journal reference: Proceedings of the Royal Society B: Biological Sciences (DOI: 10.1098/rspb.2007.0316)

Nonsense mutations put premature “stop” signals in the middle of genes, causing the cells’ protein-making machinery to stop too early. The non-functional proteins that result contribute to diseases such as cystic fibrosis and Duchenne muscular dystrophy. DMD, for example, is caused by a lack of the protein dystrophin, which helps maintain muscle fibre strength

Lee Sweeney at the University of Pennsylvania in the US and colleagues previously found that the antibiotic gentamicin could overcome the nonsense mutations responsible for around 15% of DMD cases. However, the drug proved too toxic, so Sweeney’s team screened 800,000 molecules to develop a drug called PTC124.

Restored muscles

In a mouse model of DMD, PTC124 increased levels of functional dystrophin and restored muscle function.

Like gentamicin, PTC124 prevents ribosomes from recognising the “stop” signals in messenger RNA (messenger RNA carries the blueprint for building a protein to the ribosomes, which are the cell’s protein-making factories).

Sweeney says the drug works by altering ribosomes to increase the frequency at which they can read through premature stop signals, allowing a therapeutic amount of functional protein to be made.

But unlike gentamicin, the drug does not affect normal stop signals, so it could be safer to use.

Safety check

Sweeney says that PTC124 appears to be safe in clinical trials in patients with DMD and cystic fibrosis.

Steve Hyde who works on gene therapies for cystic fibrosis at Oxford University says the drug will be useful, but limited by whether nonsense mutations are common in the particular patient’s DNA. For cystic fibrosis this varies with ethnicity.

“In the UK it is probably only about 5% of patients, but in Jewish populations it is much higher. If I was a cystic fibrosis patient in Israel I’d be quite excited,” he says.

Journal reference: Nature, DOI: 10.1038/nature o5756