Featured Research

from universities, journals, and other organizations

Researchers Develop New Method To Help Find Deadly Malaria Parasite's Achilles Heel

Date:
November 2, 2005
Source:
University of California - San Diego
Summary:
UCSD scientists will report in the Nov. 3 issue of Nature a comparison of newly discovered protein-interactions in Plasmodium falciparum with protein interactions reported earlier in four other well studied model organisms.

Researchers at UCSD have discovered that the single-cell parasite responsible for an estimated 1 million deaths per year worldwide from malaria has protein "wiring" that differs markedly from the cellular circuitry of other higher organisms, a finding which could lead to the development of antimalarial drugs that exploit that difference.

The scientists will report in the Nov. 3 issue of Nature a comparison of newly discovered protein-interactions in Plasmodium falciparum with protein interactions reported earlier in four other well studied model organisms -- yeast, a nematode worm, the fruit fly, and a bacterium that causes digestive-tract ulcers in humans. The authors of the study, Trey Ideker, a professor of bioengineering at UCSD's Jacobs School of Engineering, and two graduate students, Silpa Suthram and Taylor Sittler, said the malaria parasite's protein interactions "set it apart from other species."

"We've known since the Plasmodium genome was sequenced three years ago that 40 percent of its 5,300 proteins are significantly similar, or homologous, to proteins in other eukaryotes, but until now we didn't know that the malaria parasite assembles those proteins so uniquely," said Ideker. "Since our earlier research showed that yeast, worm, and fly have hundreds of both conserved proteins and protein interactions, we didn't initially believe our own analysis, which showed that there are only three Plasmodium protein interactions in common with yeast and none in common with the other species studied." The World Health Organization warns that malaria is a growing threat to health worldwide, particularly in poor countries. No malaria vaccine has been developed, and once powerful antimalarial drugs are less and less effective because Plasmodium falciparum has developed resistance to those drugs. Even mosquitoes that transmit malaria are developing resistance to the most commonly used insecticides.

"The demonstration that the Plasmodium protein network differs significantly from those of several model organisms is an intriguing result that could lead to the identification of novel drug targets for fighting malaria," said John Whitmarsh, acting director of the Center for Bioinformatics and Computational Biology at the National Institute of General Medical Sciences, which partially funded the work. "Ideker and his team have demonstrated the effectiveness of a computational approach based on mathematics for understanding complex biological interactions."

Researchers studying protein expression under controlled laboratory conditions have been slowed because techniques designed for other organisms work poorly with Plasmodium because 80 percent of its genome is comprised of only two of the four building blocks of DNA.

Stanly Fields, a professor of genomic sciences at the University of Washington who invented an ingenious way to identify pairs of proteins that physically interact with one another, modified his technique and added special culture conditions to enable his group to study Plasmodium. Fields's team and collaborators at Prolexys Pharmaceuticals of Salt Lake City, UT, discovered 2,846 interactions involving 1,312 Plasmodium falciparum proteins. The team provided data on those interactions to Ideker's group earlier and also reported the results in the Nov. 3 issue of Nature.

Ideker's team applied a rigorous statistical analysis approach to the Fields group's Plasmodium data, focusing on interacting proteins that have homologs in other species. While the genomes of hundreds of species are filled with homologous proteins, Ideker and his colleagues are eager to understand how they interact with one another as part of a new approach to help in the design of drugs that disrupt proteins in pathogens while sparing patients from side-effects.

The malaria parasite has a four-stage life cycle, and the Fields group analyzed only the proteins expressed in the phase that infects human red blood cells, an infection that leads to fever, shaking chills, headache, muscle aches, and other symptoms. Ideker said critics may fault his study because only a subset of the Plasmodium's proteins is expressed in the erythrocytic stage. However, he noted that the parasite's asexual-phase is actually enriched in proteins for which homologs have been found in other species. Ideker also noted that the known protein interactions in yeast, worm, and fly represent only 20 percent of the total interactions and some of the reported interactions may be erroneous.

"All the protein networks described so far are incomplete and statistically noisy," said Ideker. "But whether they are incomplete and noisy in the same way or not, we can say with confidence that this particular stage of Plasmodium is different from the other organisms we've examined so far. It's this lack of overlap with other species that's surprising."

Ideker said the Plasmodium's membrane-protein complexes may be of particular interest. "Plasmodium presents many of these proteins to the red blood cell during infection and prior to replication," he said. "What really jumps out of our paper is the large number of membrane protein interactions in Plasmodium that are absent in other organisms. While this is potentially good news for fighting malaria, we need to know much more before we start talking about which membrane-protein interactions to target with a new drug."

###

The researchers acknowledge the following funding support: the National Science Foundation (S.S.); the National Institute of General Medical Sciences (T.I.); a David and Lucille Packard Fellowship award (T.I.); the Howard Hughes Medical Institute (T.S.); and Unilever (T.S.).


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University of California - San Diego. "Researchers Develop New Method To Help Find Deadly Malaria Parasite's Achilles Heel." ScienceDaily. ScienceDaily, 2 November 2005. <www.sciencedaily.com/releases/2005/11/051102175126.htm>.
University of California - San Diego. (2005, November 2). Researchers Develop New Method To Help Find Deadly Malaria Parasite's Achilles Heel. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2005/11/051102175126.htm
University of California - San Diego. "Researchers Develop New Method To Help Find Deadly Malaria Parasite's Achilles Heel." ScienceDaily. www.sciencedaily.com/releases/2005/11/051102175126.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
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:
from the past week

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