Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers develop new method to help find deadly malaria parasite’s Achilles heel

03.11.2005


The most deadly malaria parasite 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

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."

Rex Graham | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>