Was it a horror film or a sci-fi spoof? Fans of the 1986 blockbuster "The Fly" have been debating the issue ever since but one point has always been accepted. The underlying idea is plainly too far-fetched to be plausible: man and flies have nothing at all in common and the idea that they could exchange genes is ridiculous.
Or is it? The cover story of the scientific journal Cell (April 2, 2010) is a paper in which scientists at the Institute of Molecular Biotechnology (IMBA) in Vienna, Austria, report that human hearts and fly hearts are essentially under the control of many of the same genes. Using a model of heart failure in the fly, they present a systematic map of the genes involved in heart disease and heart failure and confirm that one of the control mechanisms they have identified really is associated with heart failure in flies, mice and in man.
500 genes involved in regulation of heart function
Heart disease represents the most common cause of death in Europe and North America but our knowledge of its genetic causes remains scant. In close collaboration with Rolf Bodmer of the Sanford-Burnham Medical Research Institute in La Jolla, California, Greg Neely in Josef Penninger's group at the IMBA has screened for genes that regulate heart function in the fly. Taking advantage of the in-house fly library VDRC (Vienna Drosophila Research Center), he found nearly 500 genes that when inhibited caused increased mortality when the flies were stressed. Penninger's collaborators at Strand Life Sciences in Bangalore, India used advanced computer methods to investigate the interconnections between the genes and the result - which looks like a super-complicated version of a city transport system - is the first global map of the genetic interactions behind heart function and heart failure.
From fly to mouse to humansAs Penninger notes, "About 35% of the hits relate to genes that are already known to be involved in heart function, so the method works. But we wanted to see what the other genes do." One of the 'novel' pathways detected was the CCR4-Not complex. This is highly conserved through evolution but the idea that it has a role in the heart was new. Neely was able to confirm that it is involved in heart function in the fly, and Keiji Kuba at the Akita University School of Medicine Global COE in Japan, generated knockout mice for Not3 gene, one of the CCR4-Not components and found that the mice developed severe heart problems when subjected to cardiac stress. What does CCR4-Not do in man? Based on the results of the work in flies, it seemed possible that mutations (variants) around the site of the human NOT3 gene could be associated with heart disease.
Working with Andrew Hicks and Peter P. Pramstaller of the EURAC-Institute of Genetic Medicine in Bolzano, Italy, and Arne Pfeufer of the Institute of Human Genetics at Technical University in Munich, who are all part of the QTSCD consortium (QT Interval and Sudden Cardiac Death), to explore this possibility using human data from ECG recordings, this idea was shown to be correct: variants over the region are associated with changes in QT interval, which predispose to sudden cardiac death.
Penninger notes with satisfaction that "Our work on flies has identified a possible cause of human heart disease that the human genetic screens had missed."
Results may yield clues to future therapies
The result confirms that Neely's screen in flies can be used to identify genes involved in heart function and heart disease in mice and humans. The screen picked up very many genes, over a hundred of which have no known function. They may also represent candidates for factors that predispose individuals to heart disease. Investigating them will involve a vast amount of work that will be performed in collaboration with groups studying heart function in flies, zebra fish, mice and men. Combining data from all of these models will give an overall picture of heart function under normal and diseased conditions - and presumably important clues to new therapeutic possibilities.
The paper "A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function" by G. Gregory Neely et al. will be publish in the April 2, 2010 issue of the journal Cell, along with a cover illustration.About IMBA
Dr. Heidemarie Hurtl | idw
Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University
Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
17.10.2017 | Life Sciences
17.10.2017 | Life Sciences
17.10.2017 | Earth Sciences