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'Gene Silencing' Discoverers Win Nobel Prize

10-02-2006 · ScienceDaily

The Prize in Physiology or Medicine for 2006 has been awarded jointly to Andrew Z. Fire and Craig C. Mello for their discovery of "RNA interference -- gene silencing by double-stranded RNA" -- a fundamental mechanism for controlling the flow of genetic information.

Keywords: gene, silencing, discoverers, win, nobel, prize, discoverer

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Advance in understanding of blood pressure gene could lead to new treatments
02-04-2007 · EurekAlert!
Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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Vascular endothelial growth factor is secreted by most tumors and has been shown to play an important role in tumor angiogenesis. RNAi is the sequence-specific, posttranscriptional gene silencing method initiated by double-stranded RNAs. We planned to find a better VEGF specific RNAi for colon cancer.
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New research says winning a Nobel Prize adds nearly 2 years to your lifespan
01-16-2007 · EurekAlert!
New research by the University of Warwick reveals that a Nobel Prize brings more than just cash and kudos -- it can also add nearly two years to your life.
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Cost-effective method for gene silencing is featured in Cold Spring Harbor Protocols
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Nobel laureate James Watson receives personal genome in ceremony at Baylor College of Medicine
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'Cooper pairs' can be found in insulators as well superconductors
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Fifty years ago, three physicists unveiled their BCS theory of superconductivity, which explained how currents of electrons can flow perpetually if they join in pairs. Those physicists, including Leon Cooper at Brown University, won a Nobel Prize for their work. Now Brown physicists have shown something surprising: the formation of Cooper pairs can not only help electric current to flow but it can also block that current. Their research appears in Science.
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Amon, Golub win cancer prize
10-03-2007 · Massachusetts Institute of Technology (MIT)
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Newly identified mechanism for silencing genes points to possible anti-cancer strategies
05-16-2007 · EurekAlert!
Scientists are only beginning to appreciate the extraordinary degree of control exercised over every step of the gene-to-protein production process. Only about 10 percent of human genes, for example, are active in a given cell at a given time, with the remaining 90 percent silenced by a various mechanisms. In a just-published study in Nature, scientists report an important new gene-silencing mechanism that points to promising potential targets for anti-cancer interventions.
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