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 New eDNA technology used to quickly assess coral reefs
18.04.2019 | University of Hawaii at Manoa

nachricht New automated biological-sample analysis systems to accelerate disease detection
18.04.2019 | Polytechnique Montréal

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>