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
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Power and Electrical Engineering
05.12.2016 | Materials Sciences
05.12.2016 | Power and Electrical Engineering