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 New technique unveils 'matrix' inside tissues and tumors
29.06.2017 | University of Copenhagen The Faculty of Health and Medical Sciences

nachricht Designed proteins to treat muscular dystrophy
29.06.2017 | 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 Waves

Computer scientists use wave packet theory to develop realistic, detailed water wave simulations in real time. Their results will be presented at this year’s SIGGRAPH conference.

Think about the last time you were at a lake, river, or the ocean. Remember the ripples of the water, the waves crashing against the rocks, the wake following...

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Nanostructures taste the rainbow

29.06.2017 | Physics and Astronomy

New technique unveils 'matrix' inside tissues and tumors

29.06.2017 | Life Sciences

Cystic fibrosis alters the structure of mucus in airways

29.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>