Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Easily paralyzed flies provide clues to neurodegeneration

05.12.2003


With a slight tweak of temperature, geneticist Barry Ganetzky’s flies drop like, well, flies.



For 25 years, Ganetzky has been identifying, breeding and studying a raft of fly mutants that, when exposed to minor temperature change, become completely paralyzed. The flies, which quickly recover when returned to room temperature, are now finding many uses in studies of human neurological disorders, drug discovery and insecticide development.

Ganetzky, a University of Wisconsin-Madison professor of genetics, and his colleagues have become the undisputed champions of finding such mutants, raising the tally to upward of 100 such strains over the years.


"At room temperature, they are almost indistinguishable from normal flies," says Ganetzky of the genetic variants of the fly species Drosophila melanogaster, a workhorse of modern genetics and molecular biology. But if you expose them to slightly elevated temperatures in the range of human body temperature, "in less than 10 seconds, some mutants are completely paralyzed. Others become totally incapacitated by convulsive seizures. It’s like flipping a switch. All we change is one variable - temperature."

The effect is a rapid loss of normal motor activity.

Such a handy model, Ganetzky explains, has tremendous potential for studies of disorders such as epilepsy, muscular dystrophies and a range of other neuromuscular disorders. What’s more, the flies promise a window to identifying genes - many of which have human counterparts - involved in neural function and disease.

"Because the molecular mechanisms of neural function are highly conserved, whatever we learn from studying flies is likely to have important implications for humans as well," says Ganetzky.

The flies’ sensitivity to temperature provides a unique ability to control the onset of their physiological defects, and is useful in helping researchers identify specific genes that may be involved in regulating how brain cells function.

For instance, molecular analysis of one of their mutants enabled Ganetzky’s group to identify and clone a gene that encodes sodium-channel proteins in brain cells. The influx of sodium ions into brain cells through sodium channels is the essential step in generating nerve impulses.

The isolation of the fly sodium-channel gene has spurred research on insecticide development because sodium channels are key targets of commonly used insecticides, and resistance to these insecticides is often associated with mutations of this gene. Using the Drosophila gene as a probe, other labs have now cloned the corresponding genes in many other insects, including such major pests as cockroaches and mosquitoes.

Moreover, the type of ion channel deficiencies found in some of Ganetzky’s fly mutants manifest themselves in humans suffering from such afflictions as epilepsy and cardiac arrhythmias.

"Each fly (mutant) is a door or a window into some biological activity I want to understand," Ganetzky notes. "When those activities are perturbed because of a mutation, the mutant flies become paralyzed at elevated temperatures. Disruption of the same or similar functions in humans could also produce some type of disease manifestation. As a result, these mutants potentially give us some insight into these disorders."

As one example, Ganetzky’s group discovered and cloned a human gene known as Herg. That gene was the counterpart to one of the fly genes identified among their many mutants. In humans, mutations of Herg cause a cardiac arrhythmia that can result in ventricular fibrillation and sudden death. Dozens of labs worldwide are now investigating Herg and the potassium channel protein it encodes.

Such discoveries have engendered significant interest on the part of the pharmaceutical industry. For instance, in the United States all drugs now headed to market must be screened to ensure that they do not perturb the function of Herg channels and possibly cause heart problems in patients. The tendency to affect such channels was the reason that Seldane, a popular asthma medication, was pulled from the market.

Adding to the mutant flies’ cachet, recent work by Ganetzky and post-doctoral fellow Michael Palladino showed that some of the mutants in their collection undergo progressive, age-dependent neurodegeneration resulting in the widespread death of brain cells.

"The neuropathology observed in these mutants is very reminiscent of that in human disorders such as Alzheimer’s disease and Parkinson’s disease," says Ganetzky. "Such disorders are a growing human health concern, but the underlying cellular mechanisms are still poorly understood. These mutants should provide us with valuable new insights into the molecular basis of neurodegeneration in both flies and humans."

Ganetzky believes his collection of fly models, which has been licensed by the Wisconsin Alumni Research Foundation, could become a rich resource to help pharmaceutical companies identify new biological targets and develop new high-volume screens for drug development.

"I think the mutants have real value to give us novel information about neural disorders and human disease," Ganetzky asserts. "We can’t even begin to guess what new insight might be lurking in these flies."


###
Terry Devitt 608-262-8282, trdevitt@wisc.edu

Terry Devitt | EurekAlert!
Further information:
http://www.wisc.edu/

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>