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 Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

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...

Im Focus: Breaking: the first light from two neutron stars merging

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....

Im Focus: Smart sensors for efficient processes

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...

Im Focus: Cold molecules on collision course

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...

Im Focus: Shrinking the proton again!

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>