Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps research scientists observe human neurodegenerative disorder in fruit flies

26.06.2009
The new breed of insects may help society better understand and treat Charcot-Marie-Tooth disease

A team of scientists from The Scripps Research Institute, Katholeike Universiteit Leuven, and the University of Antwerp, Belgium, among other institutions, has created a genetically modified fruit fly that mimics key features of Charcot-Marie-Tooth disease, a common neurodegenerative disorder that strikes about one out of every 2,500 people in the United States.

As described in an article published in an Early Edition of the journal Proceedings of the National Academy of Sciences the week of June 22, 2009, the work will enable scientists to study the development of the disease in powerful new ways. This work may reveal new information on how the disease develops in humans, and it will provide researchers with a tool for discovering potential new drugs to treat the disease.

Named for the three physicians who first identified the disease in 1886, Charcot-Marie-Tooth is one of the most common inherited neurological disorders in the United States today. When people have this disease, some lose the protective covering on their nerves called myelin. This causes a host of problems that usually emerge in early adulthood, including loss of muscle mass, pain and sensitivity, foot deformations, and walking difficulties.

After the human genome was solved a few years ago, studies revealed that some people with Charcot-Marie-Tooth have mutations in their genes that make a critical human protein called tyrosyl-tRNA synthetase.

This came as a surprise to many scientists, says Paul Schimmel, who is the Ernest and Jean Hahn Professor and Chair of Molecular Biology and Chemistry and is a member of The Skaggs Institute for Chemical Biology at Scripps Research. This protein belongs to a class of molecules involved in one of the most fundamental processes in life—the culminating steps in gene expression.

Basically, when a gene is expressed, its double-stranded DNA is first transcribed into a corresponding single-stranded piece of messenger RNA. Then an enzyme called the ribosome uses the mRNA as a template to make a protein by reading out its genetic sequence and then translating it into a string of amino acids. That's where the tRNA synthetases are needed.

When building new proteins, ribosomes rely on a set of molecules called transfer RNAs (tRNAs) to supply them with the amino acids they need to construct the proteins. The tRNA synthetases are needed to attach amino acids to the tRNAs.

Sound complicated? It is. But the action of tRNA synthetases is also so essential that every creature on the planet has these molecules, which probably evolved very early on as life first emerged on Earth.

"These proteins are among the first to appear in the planet," says Schimmel, who led the current research effort. "All cells need them to grow, divide, and survive."

When mutations in tyrosyl-tRNA synthetase were linked to Charcot-Marie-Tooth disease a few years ago, scientists debated whether problems arose because the mutations interfered with tRNA synthetase's normal function, helping to express genes into proteins, or whether they arose because the mutations interfered with some other unknown function.

Schimmel had been studying this type of molecule for many years and had already discovered novel functions that had evolved over time in some tRNA synthetases, including this one. He reckoned that, if one could first show that a CMT-causing mutant synthetase was active for protein synthesis, then recreating the same disease in another organism (by putting the same mutations in the other organism's analogous gene) would demonstrate that a novel function was at play.

This is exactly what he and his scientific collaborators did. After showing that the disease was not caused by a defect in the synthetase's activity for protein synthesis, the researchers created the same mutations to the equivalent protein in the fruit fly Drosophila melanogaster, which caused the insect to develop a condition with several of the hallmarks of the human disease. This suggests that Charcot-Marie-Tooth disease is related to some fundamental and unknown function the protein plays in the development and homeostasis of the nervous system. Because the unknown function is common to both humans and flies, it probably evolved hundreds of millions of years ago before the ancient ancestors of humans and flies diverged.

What exactly this function is for is still unknown. "That is a great mystery," says Schimmel. He adds that the genetically altered fruit flies are a convenient and powerful model system that may be able to help answer this question.

In addition to Schimmel, the article, "Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot–Marie–Tooth neuropathy," was authored by Erik Storkebaum, Ricardo Leitão-Gonçalves, Inge Bosmans, Patrick Van Dijck, Koen Norga, and Patrick Callaertsa of Katholeike Universiteit Leuven, Tinne Ooms, An Jacobs, Vincent Timmerman, and Albena Jordanova of the University of Antwerp, Tanja Godenschwege and Monica Mejia of Florida Atlantic University, Leslie Nangle of Scripps Research and Tyr Pharma, and Xiang-Lei Yang of Scripps Research.

This work was supported by the University of Antwerp, Katholieke Universiteit Leuven, Research Foundation Flanders, the Belgian Federal Science Policy Office, Medical Foundation Queen Elisabeth, the Association Belge contre les Maladies Neuromusculaires, the National Institute of Child Health and Human Development, the National Institutes of Health, the National Foundation for Cancer Research, and the Fund for Scientific Research.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California with a second campus located in Jupiter, Florida. Research at Scripps Florida focuses on basic biomedical science, drug discovery, and technology development.

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>