Science: A warm Wellcome to Tayside

Golf, cake and jam aren't all Dundee

has to offer. A new biomedical research

centre is attracting top scientists from

around the world. Hilary Bower talks

to four of its key players about their work

INKE NaTHKE sits with her smiling moon-faced baby on her knee and holds what appear to be parallel conversations. In one stream she describes to me intricate investigations of molecules involved in cell migration that could provide the clue to genetic cancer; in the other she's picking the brains of anyone who passes on mortgages, homes, childcare and schools.

Inke's not downshifting. Defying the "brain drain" and Britain's reputation for meagre science resources, she and her husband Jason Swedlow, have been seduced from their ivy-clad laboratories in Harvard to join the 250 scientific movers and shakers from Britain, Europe and the US who are to populate a new pounds 13m biomedical institute in Scotland on the banks of the River Tay.

Named the Wellcome Trust Building after its chief benefactor, when the airy five-storey science centre was officially opened recently with a biochemistry department staff of 450, it gave Dundee the largest concentration of life scientists in the UK after Cambridge and Oxford. More than 1,500 people are now involved in biomedical research in this city of golf, cake and jam. And if the building's director Professor Philip Cohen has anything to do with it, this is just the beginning. "People should know that some of the best science in Britain is going on in the `Tartan Triangle' - Dundee, Edinburgh and Glasgow - and not just the `Golden Triangle' of Oxford, Cambridge, and London," says Cohen. "People are falling over themselves to come to us."

A Sassenach and Royal Society professor, Cohen moved to Dundee 25 years ago and never left. Not only has he resisted the blandishments of any number of prestigious posts overseas, he even refuses to publish in American journals, arguing it simply makes it easier for those over the pond to pretend European science is a poor relation. "We must try to reverse the `brain drain' to the US. We need to get the best people back here because they are absolutely essential for training future generations," he says.

In Dundee, Cohen and his "search" team have certainly turned brain drain into brain gain. In the past seven years they have persuaded scientists from Germany, Holland, Ireland, Italy, Switzerland and the US to join them and have stolen key players from the "Golden Triangle".

What did they have to offer them, I ask. Huge salaries?

"Absolutely not," explodes Cohen. "We offer them absolutely nothing except a congenial atmosphere and a chance to develop their science. Our philosophy is to appoint people whose work we find most exciting and who we think will be congenial as colleagues - those are the two overriding criteria.

"Some people who we have invited here were turned down by other places which couldn't see what was interesting about their work. Now our people are being offered attractive positions elsewhere all the time. One of our investigators just turned down a chair in Cambridge," he adds. Quite a coup for a not terribly rich university, with little in the way of misty- spires influence.

Scotland has long had an international reputation for medical excellence, but it's a combination of good basic science and the perfect antidote to long hours in the lab - an easier living environment - that's attracting today's high-flyers, says Professor Birgit Lane, whose own groundbreaking work on epithelial cancers and skin disorders began in Dundee. "There are seagulls outside, water and hills and open spaces and the air is fresh and clean. In the evening I can get out of the lab and drive along a stretch of water to somewhere quiet. But there is also good science being done here. In the scientific world Dundee has really moved up in recent years."

Professor Jeff Williams, who's about to move his work on the primitive organism dichtyostelium, a valuable model for tissue development, from the Imperial Cancer Research Fund laboratories in Hertfordshire, sees both his science and his salary going further.

"It's the best of both worlds, you can buy more house for your money, live well on an academic salary, in a beautiful environment, and be involved in first class science. What more could you want?"

The Wellcome Trust Building is funded by a pounds 10m donation from the eponymous charity, and the gift, thought to be the largest single charitable donation ever given to a Scottish institution, has been swelled by Scottish Enterprise Tayside and Tayside regional council who have high hopes of a biotechnology influx to boost the local economy. And Cohen's legendary persistence has extracted money from a variety of charities and sources such as the Scotch whisky Gannochy Trust, romantic novelist Dame Catherine Cookson, and Sean Connery, who has marked his love of Tayside golf by dividing the pounds 160,000 he received for a one minute walk- on in Robin Hood, Prince of Thieves between four local charities, including the Wellcome Building.

The common scientific complaint of lack of research funds appears to be non-existent in Dundee. Most of the principal investigators have even brought their own salaries (in the form of fellowships), and collectively they have won grants totalling over pounds 18m.

This will fund research across the four new divisions - molecular parasitology and biological chemistry, molecular cell biology, gene regulation and expression and developmental biology - reflecting the hottest areas of biomedical science.

"Our aim is to use fundamental science to understand the causes of diseases such as diabetes, inflammation, hereditary skin conditions, immune system defects and parasitical diseases," says Cohen. And if all his recruits fulfil their potential, he predicts, we'll be hearing much much more about science north of the border.

MIKE FERGUSON: BOLT FROM THE BLUE

Though Professor Mike Ferguson's office looks out on to the cool Grampians, his mind is in the tropics on African sleeping sickness, Chagas disease and leishmaniasis. His team are as close as any in the world to producing treatments for these devastating diseases, all spread by a particularly nasty parasite family called trypanasomatids.

Between them, these parasites cause a huge burden of illness and death. Ten to 20 million people in South and Central America are thought to be infected with Chagas disease, of whom 15 per cent will die; while epidemics of African sleeping sickness and leishmaniasis often follow conflict or disaster, killing tens of thousands. Current treatments are at best ineffective, at worst toxic, expensive and difficult to administer.

It's against this background that Ferguson and his Dundee team, using the fundamental principles of cell biology and synthesis, have revealed chinks in the parasites' armour. It started with his discovery that although the parasites are very different, their surface molecules - which carry the infection - are anchored by a common biochemical "bolt" made up of enzymes.

"If we could make a drug that prevented the parasite from assembling this `bolt', all the organisms would essentially be naked. They'd lose their surface molecules and without their surface molecules they are non- infectious," explains Ferguson. "You only need to hit one enzyme to prevent the assembly of the bolt."

Earlier this year, the team succeeded in purifying and subtly modifying two of the first candidate enzymes for stripping their parasite naked. One relates to African sleeping sickness; the other is found both in trypanosome and in the malaria parasite.

"Now, for the first time, we have isolated a molecule that will both inhibit the parasite enzyme without touching the same enzyme in humans," says Ferguson. "It's the age old principle of the magic bullet."

There's still a long way to go: hundreds of different analogues of the compounds need to be generated and tested before the right one will be found. And there is also the task of trying to attract the attention of big pharmaceutical companies more attuned to drugs saleable in the rich West than those needed in the developing world. But Ferguson is enthusiastic - and when he needs to recharge, he heads for those hills and does battle with the midges instead.

CHERYLL TICKLE: OUT ON A LIMB

Why do our arms pop out just below our shoulders? How do our legs know to grow from the base of our trunks? How come there's a thumb on one edge of our hand and a pinkie on the other? Why indeed asks Professor Cheryll Tickle, a developmental biologist on the move to Dundee.

On her office wall hangs a picture of a smiling girl wearing cowboy boots. The girl is embracing a magnificently-plumed turkey - an appropriate metaphor for Tickle, whose days are spent manipulating the delicate collections of cells that make up early chick embryos in search of answers to fundamental biological questions like "how can a ball of cells end up as something that looks like a human being?"

"It's one of the most major biological problems you can tackle," she says.

Tickle's speciality is investigating how simple cells with no particular function specialise to become the muscle, skin and bone cells needed for live and kicking limbs.

"We've got very precise arrangements of muscles, particular shapes of bones, numbers of joints, even just in a finger. All that somehow arrives out of patterns of genes and signals. We know quite a lot about these, but how we go from them to something that looks like an arm is still a big gap."

One piece in the jigsaw is the discovery that limb cells start to grow out on the orders of chemical signals sent by a ridge of cells that encircles the limb bud. These signals, Tickle and colleagues in the US discovered, are fibroblast growth factors (FGF). "We've tested it by cutting off the ridge in early embryos and stapling little beads soaked in FGF on to the limb bud. If we use enough of these beads, we can rescue limb growth. The limb grows, not absolutely perfectly, but fairly normally right to the digits."

FGF, it appears, can activate limb development anywhere on a line running down the body from the top of the arm to the bottom of the leg, says Tickle.

But before the imagination runs riot on the possibility of growing new legs for the disabled, it's important to remember that this all happens in tiny embryos. "To correct disability, you would have to identify early on that something had gone wrong with the limb and then you would have to go into the early embryo to change it. We can't do that."

What is exciting, she says, is the combination of knowledge about these signalling chemicals and the increasing ability to identify genes responsible for inherited conditions. "We're beginning to get a match-up between the experimental embryology and human conditions. For example, one of the genes we have been working with is also responsible for a human condition called Holt Oram syndrome affecting the limbs and the heart." There are also parallels with tumours - one of the FGFs important in limbs was first identified in human stomach cancer, she adds.

And in case you are wondering: thumbs develop because their early cells sit farther away from a particular set of signalling cells than proto- pinkie cells that sit close.

BARBARA SPRUCE: THE MIND-BODY LINK

Fourteen years ago Dr Barbara Spruce became addicted to a chemical called proenkephalin, one of the body's "feel good" chemicals - the natural equivalent of morphine and heroin. Her fascination took her away from her hospital job and into Imperial College. August funding bodies laughed at Spruce's hypothesis that proenkephalin was any more than brain candy, but now her laboratory in Dundee is a leader in the field of programmed cell death and on the verge of creating an entirely new form of cancer drug.

Spruce found proenkephalin, which everyone thought was only active in the brain, is present in almost all body tissues and is one of the key regulators of cell death - a mechanism crucial for life. Disruptions (causing cells to die when they shouldn't, or not to when they should) are thought to be responsible for many diseases included cancer. "We know proenkephalin promotes cell death or cell survival depending on where it is located in the cell. We also have evidence that the opioid pathways give tumour cells an advantage allowing them to over-ride the cell death programme and survive when they shouldn't. By switching off the right opioid pathways, we believe we can make a tumour cell self-destruct, without killing non- tumour cells."

Spruce's combination therapy could be ready for trial in cancer patients in six months. She also turned up another "unthinkable" proposition - that the mind-body link proposed by alternative therapists may have some basis in biochemistry.

"It's hard for a scientist to admit, but the link between these chemicals - which control moods and behaviour - and cell death sets the scene for the possibility of feedback between our emotions and health in a fundamental way. We know that under conditions of stress, abnormal levels and forms of enkephalins and endorphins float around the blood stream. If these provide an inappropriate drive to cells to survive, it's possible stress could predispose to disease. An opposite example is exercise, where enkephalins and endorphins are released perhaps in more beneficial amounts or forms. These could set up a desirable equilibrium between cell life and death which protects against disease."

JULIAN BLOW: STOPPING THE GROWTH SIGNALS

Ever photocopied a large document and found you've got a page out of order, or duplicated? Imagine the margin for error if you and several friends had to photocopy the entire Encyclopedia Britannica. That, says Dr Julian Blow, is something like our cells have to do - precisely, accurately - over and over again for perfect growth.

Given the task of making multiple copies of the 3,000 million bases that make up the human genome, it's amazing that more mistakes don't slip through, especially since, in order to get the job done quickly, numerous molecular copying "machines" - known as DNA polymerases - start duplicating the DNA from many different places at once. Not surprisingly, nature has not left this feat to chance and after years of research, Blow discovered the mechanism to keep the copying machines working efficiently.

He has found that the length of our DNA is marked with chemical tags guiding the copying procedure - a process he has called "licensing". "They can only start copying DNA where there's a tag; they have to remove a tag if they copy past it - this prevents another machine starting on a section that's been copied," explains Blow.

"One implication is we've identified a new system involved in preparing a cell to divide. So if we wanted to stop the cell division, this could be a target. DNA replication is one of the first things cells do before dividing. If you stop the licensing - and get rid of the chemical tags - a cell will probably think its DNA has been copied and not continue, which would almost certainly be a better way to try to stop cell division."

Normal cells, he adds, differ from cancer cells by going through a resting phase where the licensing tags are switched off. They are only switched on again in response to a growth signal. In future, says Blow, it's possible, that a drug that shut down the licensing proteins could shunt tumour cells into a resting phase where they may be unable to respond to the abnormal growth signals coming to it.

Suggested Topics
Arts and Entertainment

books
Arts and Entertainment
The party's over: Paul Higgins and Stella Gonet in 'Hope' at the Royal Court

theatre
Arts and Entertainment
Brendan O'Carroll as Agnes Brown in the 2014 Mrs Brown's Boys Christmas special

Broadcaster unveils Christmas schedule

TV
Arts and Entertainment
'Irritatingly Disneyfied': fashion vlogger Zoella

books
Arts and Entertainment
Matthew Bell in the new BBC series Posh People: Inside Tatler

Review: Posh journalists just can't get enough of each other

TV
PROMOTED VIDEO
Arts and Entertainment
Look out: Broad shoulders take Idris Elba’s DCI John Luther a long way
tvIdris Elba will appear in two special episodes for the BBC next year
Arts and Entertainment
Taylor Swift is dominating album and singles charts worldwide

music
Have you tried new the Independent Digital Edition apps?
Arts and Entertainment

ebooksNow available in paperback
Arts and Entertainment

ebooks
Arts and Entertainment
Kieron Richardson plays gay character Ste Hay in Channel 4 soap Hollyoaks

tv
Arts and Entertainment
Midge Ure and Sir Bob Geldof outside the Notting Hill recording studios for Band Aid 30

music
Arts and Entertainment
Look out: Broad shoulders take Idris Elba’s DCI John Luther a long way
tvIdris Elba will appear in two special episodes for the BBC next year
Arts and Entertainment
Jake Quickenden and Edwina Currie are joining the I'm A Celebrity...Get Me Out Of Here! camp
tvThe two new contestants will join the 'I'm A Celebrity' camp after Gemma Collins' surprise exit
News
The late Jimmy Ruffin, pictured in 1974
people
News
Northern Uproar, pictured in 1996
people

Jeff Fletcher found fame in 1990s

Arts and Entertainment
A scene from the new Paddington bear review

Review: Paddingtonfilm
Arts and Entertainment
Tony stares at the 'Daddy Big Ears' drawing his abducted son Oliver drew for him in The Missing
tvReview: But we're no closer to the truth in 'The Missing'
Arts and Entertainment
Henry Marsh said he was rather 'pleased' at the nomination
booksHenry Marsh's 'Do No Harm' takes doctors off their pedestal
Arts and Entertainment
All in a day's work: the players in the forthcoming 'Posh People: Inside Tatler'

tv
Arts and Entertainment
Eddie Redmayne plays Stephen Hawking in new biopic The Imitation Game

'At times I thought he was me'

film
Arts and Entertainment

books
Arts and Entertainment
One Direction go Fourth: The boys pose on the cover of their new album Four

Review: One Direction, Four

music
Arts and Entertainment
'Game of Thrones' writer George RR Martin

Review: The World of Ice and Fire

books
Arts and Entertainment
Sean Bean will play 'extraordinary hero' Inspector John Marlott in The Frankenstein Chronicles
tvHow long before he gets killed off?
Arts and Entertainment
Some like it hot: Blaise Bellville

music
Arts and Entertainment
A costume worn by model Kate Moss for the 2013 photograph

art
Arts and Entertainment

music
Arts and Entertainment
Len Goodman appeared to mutter the F-word after Simon Webbe's Strictly performance

Strictly
Arts and Entertainment
Jamie T makes his long-awaited return to the London stage
musicReview: Alexandra Palace, London
Latest stories from i100
Have you tried new the Independent Digital Edition apps?

ES Rentals

    Independent Dating
    and  

    By clicking 'Search' you
    are agreeing to our
    Terms of Use.

    Homeless Veterans Christmas Appeal: Drifting and forgotten - turning lives around for ex-soldiers

    Homeless Veterans Christmas Appeal: Turning lives around for ex-soldiers

    Our partner charities help veterans on the brink – and get them back on their feet
    Tove Jansson's Moominland: What was the inspiration for Finland's most famous family?

    Escape to Moominland

    What was the inspiration for Finland's most famous family?
    Nightclubbing with Richard Young: The story behind his latest book of celebrity photographs

    24-Hour party person

    Photographer Richard Young has been snapping celebrities at play for 40 years. As his latest book is released, he reveals that it wasn’t all fun and games
    Michelle Obama's school dinners: America’s children have a message for the First Lady

    A taste for rebellion

    US children have started an online protest against Michelle Obama’s drive for healthy school meals by posting photos of their lunches
    Colouring books for adults: How the French are going crazy for Crayolas

    Colouring books for adults

    How the French are going crazy for Crayolas
    Jack Thorne's play 'Hope': What would you do as a local politician faced with an impossible choice of cuts?

    What would you do as a local politician faced with an impossible choice of cuts?

    Playwright Jack Thorne's latest work 'Hope' poses the question to audiences
    Ed Harcourt on Romeo Beckham and life as a court composer at Burberry

    Call me Ed Mozart

    Paloma Faith, Lana del Ray... Romeo Beckham. Ed Harcourt has proved that he can write for them all. But it took a personal crisis to turn him from indie star to writer-for-hire
    10 best stocking fillers for foodies

    Festive treats: 10 best stocking fillers for foodies

    From boozy milk to wasabi, give the food-lover in your life some extra-special, unusual treats to wake up to on Christmas morning
    'I have an age of attraction that starts as low as four': How do you deal with a paedophile who has never committed a crime?

    'I am a paedophile'

    Is our approach to sex offenders helping to create more victims?
    How bad do you have to be to lose a Home Office contract?

    How bad do you have to be to lose a Home Office contract?

    Serco given Yarl’s Wood immigration contract despite ‘vast failings’
    Green Party on the march in Bristol: From a lost deposit to victory

    From a lost deposit to victory

    Green Party on the march in Bristol
    Putting the grot right into Santa's grotto

    Winter blunderlands

    Putting the grot into grotto
    'It just came to us, why not do it naked?' London's first nude free runner captured in breathtaking images across capital

    'It just came to us, why not do it naked?'

    London's first nude free runner captured in breathtaking images across capital
    In a world of Saudi bullying, right-wing Israeli ministers and the twilight of Obama, Iran is looking like a possible policeman of the Gulf

    Iran is shifting from pariah to possible future policeman of the Gulf

    Robert Fisk on our crisis with Iran
    The young are the new poor: A third of young people pushed into poverty

    The young are the new poor

    Sharp increase in the number of under-25s living in poverty