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 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Flying: Efficiency thanks to Lightweight Air Nozzles

23.10.2017 | Materials Sciences

Salmonella as a tumour medication

23.10.2017 | Life Sciences

50th Anniversary at JULABO GmbH

23.10.2017 | Press release

VideoLinks
B2B-VideoLinks
More VideoLinks >>>