The MRC PPU's collaboration with the pharmaceutical industry has won a prestigious Queen’s Anniversary Prize for Higher Education.
The award recognises the work of the Division of Signal Transduction Therapy (DSTT) - a unique consortium bringing together the research expertise of 12 research teams, 8 in the MRC PPU and 4 in the School of Life Sciences at Dundee. The collaboration with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck & Co, Merck KGaA and Pfizer helps to accelerate the development of new drugs to combat major diseases including cancer and diabetes.
The announcement was made on 17 November 2005 by Founder and Chairman of the Royal Anniversary Trust Mr Robin Gill CVO at a ceremony at St James’s Palace attended by DSTT Co-directors Philip Cohen (MRC PPU) and Peter Downes (SLS) and Sir Alan Langlands, Principal of the University of Dundee.
Alan Langlands said: “We are honoured that the work of our life scientists in this important area has been recognised with such a prestigious award. The DSTT is a unique, extraordinary and highly successful operation which is enabling the discovery of new drugs to treat major global diseases. It is a great tribute to the drive and vision of Philip Cohen, Peter Downes and other leading scientists, that the DSTT has gone from strength to strength in spite of the complexities, not only of the science, but of the international business environment in which it operates.”
Secretary of State for Education and Skills, Ruth Kelly said, “I would like to congratulate the winners of The Queen's Anniversary Prizes for Higher and Further Education. The breadth of their achievement is an outstanding testament to the remarkable work being done by universities and colleges in the UK. They clearly demonstrate that we can be proud of our educational institutions and of the expertise and commitment to excellence of those who teach in them.'
The award will be made by the Queen at Buckingham Palace on February 16th 2006.
David Komander, a former PhD student with Dario Alessi and Daan van Aalten, has been awarded the Karl-Lohmann Prize of the Gesellschaft fuer Biochemie und Molekularbiologie (GBM, German Association for Biochemistry and Molecular Biology). This bi-annual prize is awarded to a German scientist under 35, for their important contributions in biological chemistry during the PhD or postdoctoral period. David will receive his award and present a talk at the autumn-meeting of the GBM in Berlin.
There was much excitement in 2001 when elegant clinical investigations undertaken by Richard Lifton’s research group at the Yale University School of Medicine, New Haven reported that the WNK1 and WNK4 protein kinases, were mutated in patients that suffered from a severe inherited hypertension syndrome called “Gordon Syndrome”. As the function of WNK kinases was unknown, Alberto Vitari, a PhD student in the MRC Unit, decided to undertake the challenge of identifying physiological substrates for the WNK1 and WNK4 enzymes, as this might provide new clues as to how hypertension is regulated at the molecular level. Alberto made the interesting discovery that WNK1 and WNK4 interacted with high affinity with two other closely related protein kinases in cells that were termed SPAK and OSR1. Alberto then found that SPAK and OSR1 were efficiently phosphorylated by WNK1 and WNK4 and most interestingly, the activity of SPAK and OSR1 was hugely enhanced following phosphorylation with WNK1 and WNK4. Fascinatingly, SPAK and OSR1 were previously reported to be activated in cells in response to osmotic stress such as high salt and phosphorylate and regulate the activity of ion transporters such as NKCC1. It had also been previously shown that treatment of cells with high salt concentration activated WNK1. Putting this data together with Alberto’s results, suggest that osmotic stress control the activity of ion transporters through the WNK-SPAK/OSR1 pathway (see Fig). It is possible that mutations in WNK1 and WNK4 genes in humans disrupt this pathway, thereby affecting ion transporter activity in organs such as the kidney, which could account for the development of hypertension in subjects with these mutations.
Click here to access Alberto’s paper.
Many cancers possess an elevated activity of the protein kinases PKB/Akt and S6K, which is believed to drive the proliferation, growth and survival of these cells. Pharmaceutical companies are devoting a considerable effort to develop drugs that would inhibit PKB and S6K activity for the treatment of such tumours. We have speculated that drugs that inhibit PDK1 might have anti-cancer properties, but there was little evidence to support this notion. In order to test this hypothesis, Jose Bayascas in our Unit, generated mice that express approximately 10-fold lower levels of PDK1 similar to the situation of an animal treated with a specific PDK1 inhibitor.
Jose crossed these mice to PTEN+/- mice that develop numerous tumours as a result of having elevated PKB and S6K activity. Excitingly, Jose in collaboration with Stewart Fleming at Ninewells Hospital, discovered that the PTEN+/- mice with reduced expression of PDK1, were markedly protected from developing a wide range of tumours. These findings provide strong evidence that PDK1 is a central mediator of cancer resulting from loss of PTEN and also suggest that PDK1 is a promising anti-cancer target for the prevention of tumours that possess elevated PKB and S6K activity. We hope that this study will motivate pharmaceutical companies to develop PDK1 inhibitors for cancer therapy. For a copy of Jose's paper click here
The European Molecular Biology Organisation announced on October 6th that they have awarded Dario The EMBO Gold Medal for 2005 for his “pioneering research on enzymes called kinases and their role in inherited disease which has provided exciting new insights into conditions such as cancer, diabetes and hypertension”. Dario was presented with the Gold Medal and a bursary of 10,000 Euros at the EMBO Frontiers of Molecular Biology meeting in Warsaw Poland on October 16th. The EMBO Gold Medal is widely regarded as the most prestigious research prize in Europe for a Life Scientist under the age of 40 and follows a number of other young investigator awards that Dario has received over the past few years.
Recipients of the EMBO Gold Medal are also honoured as role models for other young scientists in Europe. EMBO stated that “Dario Alessi fulfils these criteria on every level.Just 14 years after completing his PhD, he is a leading light in the world of cell signalling. His discovery and characterisation of the PDK1 and LKB1 kinases has had a major impact on understanding of signal transduction. These breakthroughs and Alessi’s continued research in this area also hold great promise for the clinical treatment of inherited diseases.”
EMBO Executive Director, Frank Gannon commented “Dario is an exemplary role model for young researchers having achieved so much in his still young research career. His work has had a tremendous international impact and this is all the more remarkable when you consider his publication approach, which steers away from high impact journals. To do this and still achieve such an impact on biomedical research is the mark of a truly exceptional scientist.”
On hearing of his award Dario said “it is an enormous honour to be selected by EMBO for this award and to be the first researcher in Scotland to receive this accolade. The European aspect of the award is very special to me. With Scottish and Italian parents, a Spanish wife and a childhood spent in France and Belgium, I have a strong European sense of identity. To gain the recognition of such an esteemed group of European scientists is also a great privilege.”
Sir Philip Cohen, Director of the MRC Protein Phosphorylation Unit in which Dario works said “this award is a great honour for Dario and for our Unit. It is really deserved for the remarkable series of discoveries that Dario has made in only eight years after becoming a Programme Leader in the Unit.”
On September 12-14 the Unit hosted an international meeting on ‘cell signalling and disease’ between the United Kingdom and Research Institutes in Texas. The meeting was organised and funded by the Department of Trade and Industry in London who also awarded a prize for the best three posters presented by a graduate student or a post doc. The posters were judged by a team of four, two from Texas and two from the UK. All three prizes were awarded to Dundee based researchers. Two students in the Unit, Claire McCoy (from Simon Arthur's lab) and Alberto Vitari (from Dario Alessi’s lab) were awarded two of the prizes. The third was awarded to Sharon Matthews (a post doc in Doreen Cantrell’s lab) in the School of Life Sciences at the University of Dundee. The awardees each received a cheque for £150.00.
A gala day organised by Camperdown Lodge raised £1700 for Diabetes Research, and the cheque was presented to Dario Alessi and Kei Sakamoto by members of the Lodge on 29 August.
This is the second year that Camperdown Lodge has raised money to support research in Dario's laboratory, and the funds raised will go towards enabling a promising student from anywhere in the world to come to Dundee to gain expertise and knowledge in diabetes research.
Ten Programme Leaders based in the major life science centres of Dundee, Edinburgh and Glasgow, and including Nick Morrice, Head of Proteomics in the MRC Protein Phosphorylation Unit, have been awarded the UK’s Interdisciplinary Research Collaboration in Proteomic Technology (IRCPT). The grant of £10.8 M over the next 6 years will fund postdoctoral and technical positions in the participating laboratories to develop methods for analysing protein complexes, identifying post-translational modifications in proteins and determine protein-drug interactions. Nick Morrice, who spearheaded the Dundee bid, will use the three positions he has been awarded to focus on problems that are crucial to the current research programmes of the Unit. In addition to the £10.8 M the IRCPT has also been awarded a further £0.9 M to fund a centre for the training of PhD students in this area and £0.9M to enhance infrastructure. The total amount awarded to Nick Morrice to fund staff positions and equipment for his research was £1m.
As part of the five year review of its research, the Unit provide the UK Medical Research Council with information about the careers of the postdoctoral researchers and research students that it has trained. This analysis has been carried out recently and turned up the following impressive information:-
54 students and postdocs who were trained in our Unit are now running their own Research Groups in Universities or Research Institutes. Of these, 21 have their laboratories in the UK, 13 in the USA, five in Spain, five in Canada and one each in Australia, France, Germany, Hungary, Italy, Malaysia, Portugal, Singapore, Sweden, Poland and Switzerland. Fifteen of those based in Universities have reached the level of full Professor and eight have founded biotechnology companies, three of which are in the UK. 20 other former students and postdocs have made their careers in the pharmaceutical and biotechnology industry. Most of the remainder are still carrying out further postdoctoral training.
Many of our former students and postdocs have become international leaders in their field and two are listed in the world's 100 most cited scientists in the field of Biology and Biochemistry over the last 10 years, They are Dario Alessi at position 13 and Brian Hemmings at 62 (Thomson Scientific, Philadelphia).
Philip Cohen, the MRC Unit's Director, recently had two surprise celebrations for his 60th Birthday in July, one in Colorado, USA and the other in Dundee.
The Colorado celebrations occurred when Philip was attended the FASEB Meeting on Protein Kinases in Snowmass, and the organisers secretly organised a birthday party.
In Dundee, Philip was again taken by surprise when Unit staff and students arranged a party for him. Among the gifts Philip received was a portrait drawn by a member of the Unit, two bottles of Special Edition Edradour whiskey, and a birthday cake depicting a few of his hobbies.
One of the Unit’s papers has just been named by the Biochemical Journal as their most highly cited paper published in 2003 with 191 citations as of 14 July 2005. The paper entitled 'The specificities of protein kinase inhibitors: an update' (Bain et al) described the specificities of a number of protein kinase inhibitors and was a follow up to another of the Unit’s papers entitled 'Specificity and mechanism of action of some commonly used protein kinase inhibitors' (Davies et al) which was published in 2000. According to the Biochemical Journal, the paper by Davies et al has been cited 1107 times and is the most cited paper published in the Biochemical Journal for the year 2000. This paper was also the most frequently downloaded original paper from the Biochemical Journal website in 2004 (7617 times).
Luke Hesson, who recently joined Philip Cohen's Group as a postdoc, visited the House of Lords on 8 June 2005 as a member of the research team at the University of Birmingham, who received the "Team of the Year 2004" award from the Breast Cancer Campaign.
This award is granted to the research team who have been most successful in publishing and presenting the results of their research, and for their continued commitment into researching the cure for breast cancer. One of the main interests of the team, led by Professor Farida Latif , is the study of the RASSF family of tumour suppressor genes, which are proapoptotic K-ras effectors. As part of this team Luke Hesson helped to identify interacting partners of the tumour suppressor gene RASSF1A. He then went on to identify, clone and characterise other members of the RASSF gene family and found that several, like RASSF1A, were inactivated by promoter DNA hypermethylation in several forms of cancer, including breast cancer. In an effort to understand the roles of these other RASSF members in tumourigenesis he then went on to investigate their function using the yeast two-hybrid system. His research provides possible diagnostic markers for early detection of a range of cancers as well as identifying therapeutic targets for the inhibition of cancer cell growth.
In April 2005 at a special fundraising dinner held in New York for the new Research Building at the University of Dundee, Sherry Snyder, the CEO of Upstate presented Philip Cohen, Director of the MRC PPU at Dundee with an engraved vase in recognition of the major impact that the University has made in Cell Biology worldwide.
Edmond Fischer, the 1992 Nobel Laureate for Medicine or Physiology and co-discoverer with Edwin Krebs of Reversible Protein Phosphorylation as a control mechanism in 1955, visited Dundee from March 8th – 10th 2005 to celebrate the 50th Anniversary of his seminal finding. Eddy presented the 10th Dundee Cell Signalling Lecture on March 10th, which was preceded by the ‘Eddy Fischer Scientific Dynasty Symposium’ featuring lectures by some of his scientific ‘grandchildren’ and ‘great-grandchildren’.
The 50th anniversary of Protein Phosphorylation and Eddy’s 85th birthday were then celebrated in style with a dinner at Glamis Castle on the evening of March 10th, attended by all the Team Leaders in Dundee working on aspects of protein phosphorylation as well as by representatives of the six major pharmaceutical companies with whom the MRC Unit collaborates. Also present were the CEO and CFO of local Biotechnology Company, Upstate, who sponsored Eddy’s lecture. Mary, Dowager Countess of Strathmore, and mother of the present Earl of Glamis who owns the castle also attended the dinner.
The MRC Protein Phosphorylation Unit has had a mutually beneficial commercial collaboration with Upstate Inc over the past 11 years, which in 1999 led to Upstate setting up the European division of the company in Dundee. The Dundee based company has been extremely successful, has grown to 78 staff and was a major reason why Upstate was acquired by Serologicals of Atlanta in October 2004 for $205 million. Upstate now operates as an independent Division of Serologicals, which is capitalised on the NASDAQ index in the USA.
Further expansion of Upstate Dundee will now take place, following construction of a new building, which was officially opened by Scottish Executive Deputy First Minister, Jim Wallace on March 8th 2005. The opening of the building was also attended by Edmond Fischer, the 1992 Nobel Laureate for Medicine or Physiology, whose discovery of Reversible Protein Phosphorylation as a control mechanism opened up the area of research that is Upstates’core business. When Jim Wallace pulled the cord to unveil a plaque, Eddy Fischer was amazed to see that the new building had been named after him, a very nice surprise! Upstate will consolidate all their UK operations in the new building in Dundee, relocating their assay development group from Cambridge, UK and their marketing from Milton Keynes, UK.
Philip Cohen received the Distinguished Service Award at the Nature Miami Winter Biotechnology Symposium, February 6th-9th 2005. The meeting, entitled ‘Protein Kinases in Cancer Drug Discovery’, also celebrated the 50th Anniversary of the discovery of Reversible Protein Phosphorylation as a control mechanism by Edmond Fischer and Edwin Krebs, who jointly received the Lifetime Achievement Award at the meeting. The award was presented to Eddy Fischer at the meeting banquet on February 8th by Philip, who was Master of Ceremonies for the evening. As part of the award, Eddy Fischer and Ed Krebs each received a golden guinea from the reign of King George III, while Philip’s award included a new driver to help improve his golf game!
Commenting on the award, Philip said “You only have to look at recent recipients of the Distinguished Service Award to see what a great honour it is to have received it. In the previous three years it has been awarded to four legendary molecular biologists, Sidney Brenner in 2002, Francis Crick and James Watson in 2003 and Aaron Klug in 2004.”