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From a lowly yeast, researchers divine a clue to human disease

12-07-2006 · EurekAlert!

Working with a common form of brewer's yeast, University of Wisconsin-Madison researchers have uncovered novel functions of a key protein that allow it to act as a master regulatory switch -- a control that determines gene activity and that, when malfunctioning in humans, may contribute to serious neurological disorders.

Keywords: lowly, yeast, researchers, divine, clue, human, disease, researcher

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Assumption of function not always correct
05-01-2007 · EurekAlert!
A protein called RecQ takes on a totally opposite function in the bacteria Escherichia coli to the one it fulfills in yeast and in humans, indicating that people seeking to understand the role of different forms in human cells and disease need to consider both possibilities, said researchers from Baylor College of Medicine in a report in the current issue of Molecular Cell.
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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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Rhesus macaque genome may hold clues for human health and evolution
04-12-2007 · EurekAlert!
An international consortium of scientists has completed a draft sequence of the rhesus macaque genome, a species of non-human primate widely used for creating models of human diseases and infections. The study paves the way for researchers to watch disease progression at the genetic level in macaques, a close relative of humans. The findings, which appear April 13 in the journal Science, will let us learn how humans and other primates evolved into distinct species.
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New vaccine prevents CMV infection and disease in mice
06-22-2007 · EurekAlert!
Researchers at the University of California, San Diego (UCSD) Skaggs School of Pharmacy and Pharmaceutical Sciences have patented a strategy for developing a human vaccine to prevent against Human Cytomegalovirus (hCMV) infection and disease.
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Huntington's disease study shows animal models on target
07-31-2007 · EurekAlert!
An international team of researchers has published a benchmark study showing that gene expression in several animal models of Huntington's disease closely resembles that of human HD patients.
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Mutant sperm guide clinicians to new diseases
12-02-2007 · EurekAlert!
New research published in Nature Genetics shows that some rearrangements of the human genome occur more frequently than previously thought. The work is likely to lead to new identification of genes involved in disease and to improve diagnosis of genomic disease. Researchers from the Wellcome Trust Sanger Institute looked at four regions in the genome where rearrangements cause so-called "genomic disorders," and found that some rearrangements were found in sperm much more frequently than expected.
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Some key laboratory breast cancer cell lines are, indeed, good models for the 'real' disease
11-02-2006 · EurekAlert!
In this era of molecular medicine, controversy among cancer researchers is increasing as to whether the laboratory cells they study -- and upon which human treatment is based -- accurately reflect the biology of "real" tumors growing in a person's body.
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11-30-2006 · EurekAlert!
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Infectious disease researchers develop basis for experimental melanoma treatment
12-07-2006 · EurekAlert!
While investigating a fungus known to cause an infection in people with AIDS, two grantees of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, unexpectedly discovered a potential strategy for treating metastatic melanoma, one of the deadliest forms of skin cancer. The treatment approach, which involves combining an antibody with radiation, has since been further developed and is expected to enter early-stage human clinical studies in 2007.
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Gene found for rare disorder may reveal new pathway in mental retardation
02-05-2007 · EurekAlert!
Studying mutations that give rise to a rare genetic disease, genetics researchers have identified a novel biological pathway that may have a broader role during human development, potentially in cases of mental retardation and autism. An international team of researchers identified two genes that contribute to Cornelia deLange syndrome, a multisystem genetic disease that affects an estimated one in 10,000 children.
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