The image on the 2003 MRC Christmas/New Year card is a painting inspired by the research of our Unit. The artist is Dr Lizzie Burns, who is based in the Department of Biochemistry at the University of Oxford. The picture is entitled "Insulin binding with a cell, triggering waves of phosphorylation".
The MRCPPU therefore takes this opportunity to wish all the readers of this website a Happy New Year.
According to the Institute for Scientific Information in Philadelphia (ISI), a study published in 1995 by three of the Unit’s PIs (Dario Alessi, Ana Cuenda and Philip Cohen) in collaboration with David Dudley and Alan Saltiel of the Parke-Davis Pharmaceutical Company (now part of Pfizer) was the UK’s most highly cited original research paper over the past ten years in the field of Biology and Biochemistry. The paper, published in the Journal of Biological Chemistry 270, 27489-27494, has been cited 1968 times by other scientists. It identified the mechanism action of PD 98059, a specific inhibitor of the classical MAP kinase cascade, PD 98059 has been used very widely to block signalling through this pathway. More potent drugs that act in a similar way are undergoing human clinical trials as anti-cancer agents.
With 1016 citations, another paper published in 1995 by three of the Unit’s PIs (Ana Cuenda, John Rouse and Philip Cohen) in collaboration with John Lee and Peter Young at SmithKlineBeecham (now GlaxoSmithKline) was the UK’s fourth most quoted original research paper in Biology and Biochemistry over the past ten years. Published in FEBS Letters 364, 229-233, it showed that the compound SB 203580 is a potent and specific inhibitor of the protein kinase now termed p38 MAP kinase. At least four pharmaceutical companies have inhibitors of p38 MAP kinase in human clinical trials for the treatment of rheumatoid arthritis and other chronic inflammatory diseases. The discovery of p38 MAP kinase itself by John Rouse and Philip Cohen in 1994 in collaboration with Angel Nebreda and Tim Hunt at the ICRF, London (Cell 78, 1027-1037) was cited 971 times, making it the UK’s 8th most quoted paper in the field of Molecular Biology and Genetics.
A further paper in 1995 published by Darren Cross, Dario Alessi and Philip Cohen in collaboration with Brian Hemmings at the Friedrich-Miescher Institute, Basel, Switzerland (Nature 378, 785-789) was the UK’s sixth most cited paper in the field of Biology and Biochemistry with 962 citations. It identified PKB/Akt as the protein kinase that mediates the insulin-induced inhibition of GSK3 and consequent stimulation of glycogen synthesis. Small molecule inhibitors of GSK3 developed subsequently by several pharmaceutical companies have been shown to normalise the level of blood glucose in animal models of Type II diabetes. The 1997 paper by Dario Alessi and Philip Cohen identifying PDK1 as the protein kinase that activates PKB/Akt has so far been cited 588 times, making it Scotland’s fifth most cited paper of the past ten years. Overall, the Unit’s PIs co-authored three of the top ten UK papers in Biology and Biochemistry and five of the Scotland’s seven most cited papers in this field over the past decade.
Tricia Cohen and Carol MacKintosh, two other PIs in the MRC Unit were also ranked in the top 1% of most cited scientists in their fields, Tricia in “Molecular Biology and Genetics” and Carol in “Plant and Animal Siences”.
The Unit is affiliated to the School of Life Sciences at Dundee which, in terms of citations per paper, came out as the number one University in Europe in the fields of Biology and Biochemistry and the number two in Europe (after the University of Geneva) in the field of Molecular Biology and Genetics.
According to the latest information from ISI, Philip Cohen is now the world’s third most highly cited scientist over the past 10 years in the field of Biology and Biochemsitry, while Dario Alessi moved up from number 44 in the list to number 30 over the past two months.
In November 2003, Gopal Sapkota, a former PhD student with Dario Alessi, was awarded a Damon Runyon postdoctoral fellowship by the Damon Runyon Cancer Research Foundation. Gopak was one of 19 recipients of this prestigious award, selected from a pool of 159 candidates.
Gopal will commence his research with Dr Joan Massague at the Memorial Sloan-Kettering Cancer Center in New York on 1 January 2004.
Founded in 1946, the Damon Runyon Cancer Research Foundation has gained worldwide prominence in cancer research by identifying outstanding young postdoctoral scientists and providing them with financial support for their research.
On 28 November the University of Dundee received The President's Award for 2003 from the Scottish Council for Development and Industry (SCDI). This is the SCDI's premier award and was made to the School of Life Sciences and the Medical School in recognition of their achievement in building up life sciences research and biotechnology into a major industry in Dundee, which now accounts for 12-14% of the local economy.
The award was collected on behalf of the University by Philip Cohen and David Lane.
On 17 November at the London Marriott Hotel in Grosvenor Square, Mayfair, Sir Philip Cohen was made an Honorary Member of the British Biochemical Society together with Nobel Laureate Sidney Brenner and Sir Alec Jeffreys, all of whom received specially engraved silver salvers.
Commenting on the award Sir Philip said "The British Biochemical Society has over 7,000 members and has only awarded honorary membership to 26 people over the past 35 years. Having looked at the list, which includes 10 Nobel Prize winners, it is clearly a tremendous honour to have received this award."
Sir Philip is the only scientist in Scotland to have received Honorary Membership of the British Biochemical Society.
Dr Jean Harthill, a postdoctoral researcher in Carol Mackintosh's lab was one of two finalist in the "sunshine" category of the Women Who Mean Business Awards, which were presented at a dinner at the Invercarse Hotel, Dundee on 14 November. The Women Ahead awards recognise and celebrate the achievements of local women in business. Jean was nominated by colleagues in the Unit for her fundraising and charity work. For the past few years Jean has participated in a number of sponsored cycle runs.
The Sunshine award is presented to someone who has devoted a substantial amount of her own time to voluntary/charity work and has been an inspiration to others.
Tricia Cohen, Group Leader in the MRC-PPU, won the Rui Handicap Golf Tournament, a 36 hole event played on the Isla Canela and Benamore courses in southern Spain over 5 and 6 November 2003. Tricia was six shots clear of the lady competitor in second place.
Sonja Flott joined the Unit in October 2003, having been awarded a prestigious Medical Research Council (MRC) Predoctoral Fellowship. The Predoctoral Fellowship scheme is a £1 million initiative from the MRC launched in October 2000 introducing salaried stipends to outstanding students who wish to conduct PhD studies in MRC Units and Institutes. This is the third consecutive year that the MRC Protein Phosphorylation Unit has secured one of these fellowships, only 9 of which were awarded this year for the whole of the UK.
Sonja transferred to Dundee University from the University of Bochum in Germany in 2002 and worked in the laboratory of Neil Perkins in the Wellcome Trust Biocentre for her diploma thesis.
Sonja has now joined the laboratory of John Rouse in the MRC Unit to decipher the molecular mechanisms whereby the ATR protein kinase triggers the cellular response to DNA damage.
Dario Alessi and Grahame Hardie combined their scientific expertise to crack an important scientific problem.
Their research, published in The Journal of Biology on 24 September, may lead to the development of improved drugs to treat diabetes.
Dario and Grahame have discovered that a tumour suppressor called LKB1 is the long sought after enzyme that switches on AMPK, an enzyme important in regulating the level of glucose in the blood.
High blood glucose levels are a hallmark of diabetes. These levels are reduced by AMPK, which increases the rate at which glucose is transported from the blood and into muscle, and decreases the production of glucose in the liver. Drugs that can switch on AMPK, such as Metformin (also called Glucophage), are therefore commonly used to treat Type II diabetes. Until now, it was not clear how these drugs exerted their effects, but the researchers have now found that Metformin does not work if there is a deficiency of LKB1.
This fundamental new understanding of how AMPK is switched on in the body is likely to stimulate the development of improved drugs to treat Type II diabetes, which are better than Metformin at normalising blood glucose and which lack its unpleasant side effects that include stomach and intestinal problems.
Remarkably, a lack of LKB1 activity is known to be the cause of Peutz-Jeghers Syndrome, a rare inherited disease that predisposes people to many types of cancer. The discovery that LKB1 switches on AMPK therefore raises the possibility that AMPK is also important in preventing cancer and that drugs that activate AMPK may be useful for the treatment of some cancers, as well as diabetes.
Commenting on their discovery Grahame said: "The idea that LKB1 might switch on AMPK came from work I did on a related system in the simple single-cell organism, brewer's yeast with another colleague in Dundee, Mike Stark. The idea that LKB1 might be the key was a genuine 'Eureka' moment, especially when I realized that Dario already worked on it and had all of the expertise necessary to test the idea. I immediately went down the corridor to see him. That was late one afternoon, and by lunchtime the following day we had done the first successful experiment to prove the idea. If I had been working somewhere else I would probably still be struggling to do it. This shows the benefit of working in a major biomedical research centre like Dundee, where the whole is much more than the sum of its parts.
This was an extraordinary and totally unexpected result that has important implications for our general understanding of diabetes and cancer. It also demonstrates the strength of this area of research in Dundee and the importance of scientific collaboration blending the complementary expertise and knowledge from our laboratories to discover the function of the LKB1 enzyme and identify it as the long sought after enzyme that activates AMPK."
Eleanor Kennedy, Research Director at Diabetes UK said: "This is an exciting development. It holds out the prospect of new treatments which give better control of diabetes. This could mean real improvements in the lives of people with the condition. We know that good control of your diabetes reduces the risk of the long term effects such as heart disease, blindness, kidney disease and amputations. Diabetes UK looks forward to seeing whether this research can make that more possible."
The paper is live on the Journal of Biology website. http://jbiol.com/press
Dario Alessi from the Medical Research Council Protein Phosphorylation Unit has been awarded the Federation of Biochemical Societies' Anniversary Prize which he received at the FEBS meeting on Signal Transduction in Brussels on 6 July 2003.
The Anniversary prize is awarded to scientists under the age of 40 for outstanding achievement in Biochemistry and Molecular Biology. The prizes are provided by the pharmaceutical companies Boehringer Mannheim GmbH and Eppendorft Geratebau-Netheler & Hinz GmbH.
This is the seventh important award for Dario over the past four years. In 2002 he was awarded, the Royal Society of Edinburgh's Makdougall Brisbane prize for his discovery and characterisation of PDK1, the"missing link" in insulin signal transduction, The Pfizer Academic Award for his groundbreaking work on diabetes and the Young Investigator G.B. Morgagni Prize 2002 for outstanding achievements in the field of metabolism. He was also elected as a fellow of the Royal Society of Edinburgh. Dario won the Eppendorf Young European scientist of the year in 2000 and the Colworth Medal of the Biochemical Society in 1999 for young scientists under the age of 36.
Dr Axel Knebel came second in the Inaugural Gannochy Trust Innovation Award of the Royal Society of Edinburgh, which is awarded annually to a young entrepreneur under the age of 45 working in Scotland.
At the awards dinner held at Scone Palace near Perth, Scotland on 21 June 2003, Axel was presented with the silver medal by Lord Sutherland of Houndwood, the President of the Royal Society of Edinburgh. He shared the silver medal jointly with Dr Ian McEwan of the University of Aberdeen, while the winner was Dr Barbara Spruce, a former Princpal Investigator in the School of Life Sciences at Dundee, who now works in the Department of Surgery and Oncology in the Medical School at Ninewells Hospital, Dundee.
Axel was a postdoctoral fellow in the MRC Protein Phosphorylation Unit in the School of Life Sciences from 1998-2002. Working with Sir Philip Cohen over this period he developed a new method called KESTREL for identifying the substrates of protein kinases. In 2002 he became the founder and Managing Director of Kinasource Ltd, which is currently based in the Medical Sciences Institute of the School of Life Sciences. Kinasource commercialises the KESTREL technology, which has the potential to identify many novel drug targets.
The Gannochy Trust, based at Perth, is Scotland’s second largest Charitable Trust.
The Royal Society of Edinburgh, is Scotland’s National Academy for Science and the Arts. Founded in 1783 it is one of the oldest National Academies in the world.
Tricia Cohen is very pleased to announce that two of her students who started their research together have successfully defended their theses at virtually the same time. Mirela Delibegovic presented a seminar and thesis concerning "In vivo effects of insulin on the glycogen targeted forms of protein phosphatase 1" on April 25th 2003. Her viva examiners were Dr Dominic Withers (Imperial College, University of London) and Dr Hari Hundal (University of Dundee). Mirela is now a postdoctoral research assistant with Professor Ben Neel at Harvard Medical School in Boston, USA.
Shonagh Munro presented a seminar and thesis entitled " Glycogen targeting subunits of protein phosphatase1 and their role in the action of insulin" on April 28th 2003 and was then examined by Professor Miles Houslay (University of Glasgow) and Professor Grahame Hardie (University of Dundee). She has chosen to further her studies in the area of insulin action by taking up a position as a postdoctoral research assistant with Tricia funded by Diabetes UK.