Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Worm hormone discovery may aid fight against parasitic disease

13.03.2006


New research at UT Southwestern Medical Center shows that on a biochemical level, hormone-like molecules in tiny worms called nematodes work similarly to the way in which certain hormones work in humans — findings that one day may help eradicate worm infections that afflict a third of the world’s population.



UT Southwestern researchers have discovered a molecule that activates genes involved in the development and reproduction of Caenorhabditis elegans, a common research worm about the size of a pinhead.

In a study available online and appearing in the March 24 issue of the journal Cell, UT Southwestern scientists describe how the molecule, called a ligand, acts like a hormone, the first such hormonal ligand identified in C. elegans.


Like a key fitting into a lock, the newfound ligand binds to a protein in the cell’s nucleus called a nuclear receptor, a receptor designated DAF-12. Once that binding occurs, DAF-12 activates other genes that allow the worm to develop through its normal stages, reach maturity and reproduce.

When the researchers blocked that hormonal signal by engineering mutant worms that couldn’t manufacture the ligand, however, the mutants’ development stopped before they reached maturity. Instead, the worms went into a "resting" stage called the dauer diapause, in which they don’t eat or reproduce. When the researchers provided the mutants with the missing ligand, it prevented the dauer stage, and the animals continued to develop normally.

"This pathway in worms is remarkably similar to hormonal pathways in humans," said Dr. David Mangelsdorf, chairman of pharmacology at UT Southwestern and senior author of the study.

The experiments by Dr. Mangelsdorf’s team are related to how hormone-replacement therapy works in humans. For example, in patients with Addison’s disease, the adrenal glands do not produce enough of the steroids cortisol and aldosterone; in some cases, these glands produce none at all. Replacing the missing hormones through replacement therapy can relieve the symptoms of the disease, much as providing the missing ligand to the worms restored their normality.

"The conservation of this pathway is remarkable," said Dr. Mangelsdorf, an investigator in UT Southwestern’s Howard Hughes Medical Institute (HHMI). "This line of investigation has been much sought-after in terms of how the DAF-12 protein works and whether it had a hormonal regulator. Mother Nature has used this system from the very simplest nematode worms up to humans, not only employing the same types of proteins to do the job, but also the same types of hormones."

The dauer diapause occurs naturally in C. elegans when the worm senses from its environment that conditions are not favorable for maturing, such as when food is scarce. Dr. Mangelsdorf said cholesterol and other signals derived from the worm’s food source are required to launch the series of biochemical events leading to the production of the hormonal ligand and continued development. Without these environmental signals and the ligand to activate DAF-12, the worm’s life remains suspended.

The UT Southwestern research also may aid in the fight against human disease because the dauer diapause stage of C. elegans is very similar to the infective state of parasitic nematodes. According to the World Health Organization, such parasites infect about 2 billion people worldwide and severely sicken some 300 million, at least 50 percent of whom are school-age children.

In the infective state, parasitic nematodes, such as hookworms, remain in a larval, "resting" stage until they enter the human body, where they eventually migrate to the intestine and begin to mature. Dr. Mangelsdorf is investigating whether the homologue of DAF-12 in parasitic nematodes may regulate their maturing activity as well. If so, he said, the same pathway could be exploited to eradicate the pests, either by keeping them perpetually in an immature state, or by coaxing them to mature before a food source is available.

Other UT Southwestern authors on the paper are lead author Daniel L. Motola, an M.D./Ph.D. student in the Medical Scientist Training Program; Dr. Carolyn Cummins, a research fellow in pharmacology and an HHMI research associate; Dr. Kamalesh Sharma, a postdoctoral fellow in internal medicine; Tingting Li, student research assistant in pharmacology; and Dr. Richard J. Auchus, associate professor of internal medicine. Other authors were from Baylor College of Medicine and the Van Andel Research Institute in Michigan.

The research was funded by HHMI, the Welch Foundation, the National Institutes of Health, the Jay and Betty Van Andel Foundation, the Department of Defense and the Glenn/AFAR Breakthroughs in Gerontology.

Amanda Siegfried | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>