Featured Research

from universities, journals, and other organizations

Human Neurodegenerative Disorder Observed In Fruit Flies

Date:
June 25, 2009
Source:
Scripps Research Institute
Summary:
Scientists have 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.

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.

Related Articles


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.

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.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Paul Schimmel, Erik Storkebaum, Ricardo Leitγo-Gonηalves, Inge Bosmans, Patrick Van Dijck, Koen Norga, and Patrick Callaertsa, Tinne Ooms, An Jacobs, Vincent Timmerman, and Albena Jordanova, Tanja Godenschwege, Monica Mejia, Leslie Nangle, Tyr Pharma, and Xiang-Lei Yang. Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot%u2013Marie%u2013Tooth neuropathy. Proceedings of the National Academy of Sciences, June 22, 2009

Cite This Page:

Scripps Research Institute. "Human Neurodegenerative Disorder Observed In Fruit Flies." ScienceDaily. ScienceDaily, 25 June 2009. <www.sciencedaily.com/releases/2009/06/090622171501.htm>.
Scripps Research Institute. (2009, June 25). Human Neurodegenerative Disorder Observed In Fruit Flies. ScienceDaily. Retrieved December 17, 2014 from www.sciencedaily.com/releases/2009/06/090622171501.htm
Scripps Research Institute. "Human Neurodegenerative Disorder Observed In Fruit Flies." ScienceDaily. www.sciencedaily.com/releases/2009/06/090622171501.htm (accessed December 17, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Wednesday, December 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) — Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
The Hottest Food Trends for 2015

The Hottest Food Trends for 2015

Buzz60 (Dec. 17, 2014) — Urbanspoon predicts whicg food trends will dominate the culinary scene in 2015. Mara Montalbano (@maramontalbano) has the story. Video provided by Buzz60
Powered by NewsLook.com
Rover Finds More Clues About Possible Life On Mars

Rover Finds More Clues About Possible Life On Mars

Newsy (Dec. 17, 2014) — NASA's Curiosity rover detected methane on Mars and organic compounds on the surface, but it doesn't quite prove there was life ... yet. Video provided by Newsy
Powered by NewsLook.com
Ivory Trade Boom Swamps Law Efforts

Ivory Trade Boom Swamps Law Efforts

Reuters - Business Video Online (Dec. 17, 2014) — Demand for ivory has claimed the lives of tens of thousands of African elephants and now a conservation report says the illegal trade is overwhelming efforts to enforce the law. Amy Pollock reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins