- Email: [email protected]
Wellcome Trust plans for 2000–2005
110
News & Comment
TRENDS in Cell Biology Vol.11 No.3 March 2001
In Brief
Promising clinical trials on kinase inhibitor
Fig. 1. Ribbon representation of the crystal structure of the Abl kinase domain (pink) bound to an STI-571 variant (green); the inhibitor specifically recognizes the inactive conformation of the activation loop (blue). (Image courtesy of Thomas Schindler, Bhushan Nagar and John Kuriyan.)
The Philadelphia chromosome, an acquired translocation between chromosome 9 and 22, is found in 95% of patients with chronic myelogenous leukemia (CML). In these patients, overactivation of the Abelson tyrosine kinase (Abl) occurs when Abl is fused to the Bcr gene, resulting in overproliferation of white blood cells. In recent years, researchers at the pharmaceutical company Novartis used structural data on the ATP-binding pocket of Abl as a guideline to construct an Abl-specific kinase inhibitor, designated STI571 (Fig. 1). As an important step on the long road from bench to patient, encouraging results on phase II clinical studies with STI571 were presented recently at the meeting of the American Society of Haematology. White blood cell counts were back to normal in a high percentage of CML patients treated with low doses of STI571, while at higher doses the drug was even able to reduce the number of cells positive for the Philadelphia chromosome. In some patients, a complete remission of the disease was observed. Using the same structure-based strategy, researchers are currently chasing after specific inhibitors for other kinases that are involved in carcinogenesis. J.d.B.
Salary boost creates UK Science ‘Premier League’ Lord Sainsbury, the UK science minister announced the start of a scheme to attract top researchers to the UK and to halt the ongoing ‘brain drain’. The £20m fund, in
partnership with the Wolfson foundation, will allow universities to bid for ‘top-up’ funding in the region of £75 000 to be spent on salary and consumables for outstanding researchers. These funds could mean salaries in excess of £100 000 for award holders. The Association of University Teachers gave a qualified welcome to the scheme but said, ‘It does not meet the outstanding needs of research staff or attract new postgraduates into the profession. PhD students on average received £7000 a year and research staff £18 000, compared with £22 000 for London Underground station staff’. D.S.
Farmer’s research goes against the grain BSE has caused havoc in the British beef industry, and a similar disease is increasing in humans, perhaps due to eating contaminated meat. BSE is conventionally thought to have spread in cattle through feed containing infected brain tissue. A corrupted prion protein (PrP), which acts as the infectious agent, causes a conformational change in the host PrP, leading to neurodegeneration and death. However, another hypothesis is gaining credibility (see UK newspaper The Guardian, 23 Nov. 2000, http://www.guardianunlimited.co.uk/). In the1980s, the organophosphate pesticide Phosmet was used in the UK (at higher doses than elsewhere) to treat cattle for Warble-fly. Organophosphates have long been suspected of being neurotoxic, and UK dairy farmer Mark Purdey noticed a correlation between Phosmet use and BSE in his cattle. The prevalence of BSE also appeared to mirror treatment with Phosmet – which is now used less frequently in the UK but has been used in France, where the most recent BSE outbreak occurred. Purdey’s independent research shows that organophosphates chelate Cu2+ ions in the body, leading to their replacement by Mn2+ ions in PrP [Med. Hypotheses 54, 278–306, (2000)]. Additional studies from D.R. Brown in Cambridge, UK [EMBO J. 19, 1180–1186, (2000)] show that Mn2+ converts PrP to a misfolded, protease-resistant form characteristic of pathological PrP. More research is needed, but it’s worth bearing in mind that prion-based disease might be linked to environmental factors in addition to better known routes of infection. S.L.
Louis-Jeantet Prize 2001 The Louis-Jeantet Prize for Medicine, 2001, has been awarded to Iain Mattaj, the scientific director of the European Molecular Biology Laboratory in Heidelberg, Alfred Wittinghofer, a director of the Max Planck Institute for Molecular Physiology in Dortmund, and Alain Fischer, director of the clinical INSERM unit of Paediatric Immunology and Haematology at the Hôpital Necker des Enfants Malades in Paris. Mattaj will use the prize money to undertake further experiments to study the role of the small GTPase Ran in nuclear assembly following mitosis. Wittinghofer will investigate the structural biology of a newly identified class of GTP-binding proteins – the septins – and Fischer will continue his work on the application of gene therapy to immune deficiencies. The Louis-Jeantet Foundation for Medicine annually awards three outstanding biomedical scientists a cumulative sum of 1.8 million Swiss francs to carry out their new research projects beyond the scope of their existing funding. In addition, each prizewinner receives a personal award of 100 000 Swiss francs. D.S.
Wellcome Trust plans for 2000–2005
The Wellcome Trust recently published a new five-year plan. ‘Planning for the future: 2000–2005’ outlines many of the Trust’s objectives and funding strategies for the coming five years. The plan outlines the way in which the Trust’s considerable resources will be allocated in the coming years. £1.2 billion, of a total £3 billion budget, is planned for baseline funding activities, supporting innovative investigator-led proposals. As well as research funding, the document emphasizes the Trust’s commitment to training and career development of scientists as well as providing the physical conditions necessary for high-quality research. The full report is available at http://www.wellcome.ac.uk D.S.
http://tcb.trends.com 0962-8924/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
News & Comment
TRENDS in Cell Biology Vol.11 No.3 March 2001
In Brief
Promising clinical trials on kinase inhibitor
Fig. 1. Ribbon representation of the crystal structure of the Abl kinase domain (pink) bound to an STI-571 variant (green); the inhibitor specifically recognizes the inactive conformation of the activation loop (blue). (Image courtesy of Thomas Schindler, Bhushan Nagar and John Kuriyan.)
The Philadelphia chromosome, an acquired translocation between chromosome 9 and 22, is found in 95% of patients with chronic myelogenous leukemia (CML). In these patients, overactivation of the Abelson tyrosine kinase (Abl) occurs when Abl is fused to the Bcr gene, resulting in overproliferation of white blood cells. In recent years, researchers at the pharmaceutical company Novartis used structural data on the ATP-binding pocket of Abl as a guideline to construct an Abl-specific kinase inhibitor, designated STI571 (Fig. 1). As an important step on the long road from bench to patient, encouraging results on phase II clinical studies with STI571 were presented recently at the meeting of the American Society of Haematology. White blood cell counts were back to normal in a high percentage of CML patients treated with low doses of STI571, while at higher doses the drug was even able to reduce the number of cells positive for the Philadelphia chromosome. In some patients, a complete remission of the disease was observed. Using the same structure-based strategy, researchers are currently chasing after specific inhibitors for other kinases that are involved in carcinogenesis. J.d.B.
Salary boost creates UK Science ‘Premier League’ Lord Sainsbury, the UK science minister announced the start of a scheme to attract top researchers to the UK and to halt the ongoing ‘brain drain’. The £20m fund, in
partnership with the Wolfson foundation, will allow universities to bid for ‘top-up’ funding in the region of £75 000 to be spent on salary and consumables for outstanding researchers. These funds could mean salaries in excess of £100 000 for award holders. The Association of University Teachers gave a qualified welcome to the scheme but said, ‘It does not meet the outstanding needs of research staff or attract new postgraduates into the profession. PhD students on average received £7000 a year and research staff £18 000, compared with £22 000 for London Underground station staff’. D.S.
Farmer’s research goes against the grain BSE has caused havoc in the British beef industry, and a similar disease is increasing in humans, perhaps due to eating contaminated meat. BSE is conventionally thought to have spread in cattle through feed containing infected brain tissue. A corrupted prion protein (PrP), which acts as the infectious agent, causes a conformational change in the host PrP, leading to neurodegeneration and death. However, another hypothesis is gaining credibility (see UK newspaper The Guardian, 23 Nov. 2000, http://www.guardianunlimited.co.uk/). In the1980s, the organophosphate pesticide Phosmet was used in the UK (at higher doses than elsewhere) to treat cattle for Warble-fly. Organophosphates have long been suspected of being neurotoxic, and UK dairy farmer Mark Purdey noticed a correlation between Phosmet use and BSE in his cattle. The prevalence of BSE also appeared to mirror treatment with Phosmet – which is now used less frequently in the UK but has been used in France, where the most recent BSE outbreak occurred. Purdey’s independent research shows that organophosphates chelate Cu2+ ions in the body, leading to their replacement by Mn2+ ions in PrP [Med. Hypotheses 54, 278–306, (2000)]. Additional studies from D.R. Brown in Cambridge, UK [EMBO J. 19, 1180–1186, (2000)] show that Mn2+ converts PrP to a misfolded, protease-resistant form characteristic of pathological PrP. More research is needed, but it’s worth bearing in mind that prion-based disease might be linked to environmental factors in addition to better known routes of infection. S.L.
Louis-Jeantet Prize 2001 The Louis-Jeantet Prize for Medicine, 2001, has been awarded to Iain Mattaj, the scientific director of the European Molecular Biology Laboratory in Heidelberg, Alfred Wittinghofer, a director of the Max Planck Institute for Molecular Physiology in Dortmund, and Alain Fischer, director of the clinical INSERM unit of Paediatric Immunology and Haematology at the Hôpital Necker des Enfants Malades in Paris. Mattaj will use the prize money to undertake further experiments to study the role of the small GTPase Ran in nuclear assembly following mitosis. Wittinghofer will investigate the structural biology of a newly identified class of GTP-binding proteins – the septins – and Fischer will continue his work on the application of gene therapy to immune deficiencies. The Louis-Jeantet Foundation for Medicine annually awards three outstanding biomedical scientists a cumulative sum of 1.8 million Swiss francs to carry out their new research projects beyond the scope of their existing funding. In addition, each prizewinner receives a personal award of 100 000 Swiss francs. D.S.
Wellcome Trust plans for 2000–2005
The Wellcome Trust recently published a new five-year plan. ‘Planning for the future: 2000–2005’ outlines many of the Trust’s objectives and funding strategies for the coming five years. The plan outlines the way in which the Trust’s considerable resources will be allocated in the coming years. £1.2 billion, of a total £3 billion budget, is planned for baseline funding activities, supporting innovative investigator-led proposals. As well as research funding, the document emphasizes the Trust’s commitment to training and career development of scientists as well as providing the physical conditions necessary for high-quality research. The full report is available at http://www.wellcome.ac.uk D.S.
http://tcb.trends.com 0962-8924/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.