Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular models advance the fight against malaria

26.04.2005


Research from Dartmouth Medical School, demonstrating how malaria parasites form mutations that make them stubbornly resistant to drug therapy, may hold the key to a new treatments for a disease that afflicts more than half a billion people worldwide.



The scientists developed disease models using yeast and successfully introduced five mutations that make malaria resistant to the anti-malarial drug, atovaquone. The study, featured as the cover story of the April 29 Journal of Biological Chemistry, paves the way for using these models to test new drugs that could suppress malaria’s ability to mutate against current therapy. "This is the first quantitative explanation for malaria’s drug resistance," said Dr. Bernard Trumpower, professor of biochemistry at Dartmouth Medical School and head of the study. "In addition to confirming the belief that the resistance was due to these mutations, we have created a practical research tool to design new, improved versions of the drug using these resistant strains."

Malaria, transmitted by Plasmodium falciparum, a parasite carried by mosquitoes, has developed resistance to almost every anti-malarial drug introduced in the past 30 years. Although atovaquone is one of the most recent drugs on the market, there is significant evidence that malaria parasites are quickly developing resistance to that drug as well. According to WHO estimates, 40% of the world’s population are currently at risk of the disease and approximately 2 million people, mostly children, are killed by malaria annually worldwide. Today marks Africa Malaria Day, organized to promote awareness of the disease in a country where a child is killed every 30 seconds by malaria.


Investigating ways to counter the mutations and sustain the efficacy of anti-malarial drugs, Trumpower and his colleagues continued their work on previous studies using yeast enzymes to explore atovaquone resistance. It is not possible to grow enough malaria parasites to isolate and study the respiratory enzyme cytochrome bc1 complex, which the parasites need to live and multiply. A protein subunit of the bc1 complex is where the malaria parasite mutates to counter anti-malarial drug therapies. Yeast is an effective resource because it can be safely grown in large quantities and can be easily modified to take on the qualities of more dangerous pathogens, without risking human infection.

When the researchers genetically transferred mutations into the yeast surrogates, the yeast acquired resistance to atovaquone just as the malaria parasites had done. The team was then able to apply computerized modeling techniques to illustrate exactly how the drug interacted with the cytochrome bc1 complex – the respiratory enzyme the parasites need to live and multiply -- on a molecular level. With this new understanding of how the parasites were able to counter the effects of atovaquone, researchers can now design new anti-malarial drugs with features making the appearance of resistance more unlikely.

"Within the next 3-5 years, we hope to develop a new drug that will finally empower us to treat this terrible disease," said Trumpower.

Dartmouth Medical School co-authors of the paper are Dr. Jacques Kessl, research associate in biochemistry, Kevin Ha, Anne Merritt and Benjamin Lange. Other co-authors are Dr. Brigitte Meunier and Philip Hill from the Wolfson Institute for Biomedical Research in London and Dr. Steven Meshnick from the University of North Carolina, Chapel Hill.

Andrew Nordhoff | EurekAlert!
Further information:
http://www.dartmouth.edu

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>