Navigation Links
Molecular models advance the fight against malaria

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 isola te 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.


'"/>

Source:Dartmouth Medical School


Related biology news :

1. Molecular biology fills gaps in knowledge of bat evolution
2. Molecular machine may lead to new drugs to combat human diseases
3. Molecular Motors Cooperate In Moving Cellular Cargo, Study Shows
4. Molecular fossils uncover link between viruses and the immune system
5. Molecular thermometers on skin cells detect heat and camphor
6. Molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves
7. Molecular steps involved in the creation of gene-silencing microRNAs identified
8. Molecular miners find pain relief drugs from the sea
9. Molecular mechanism of feather formation found
10. Molecular trigger for Huntingtons disease found
11. Molecular Partners Required For Appropriate Neuronal Gene Repression
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:1/14/2019)... ... January 14, 2019 , ... Join the live session ... about key topics in data quality, including:, ,     State of ... ,     Smartphone and wearable based performance measures ,     Data quality analytics ...
(Date:1/10/2019)... ... 2019 , ... When Dr. James L. Sherley, M.D., Ph.D., founder and director ... chapter to the new book Perinatal Stem Cells: Research and Therapy, he knew immediately ... debilitating secret of stem cell medicine. For more than a half-century, stem cell ...
(Date:1/8/2019)... ... January 07, 2019 , ... Join industry experts Julie Peacock, Client Services at ... on Thursday, January 17, 2019 at 1pm EST. , This webinar will ... clinical trial process. Featured speakers will also present a case study of a leading ...
Breaking Biology News(10 mins):
(Date:12/5/2018)... ... December 05, 2018 , ... The incredible life story ... to in the European Parliament by Carlos Moedas, the European Commissioner for Research and ... and Innovation in Our Daily Lives, Commissioner Moedas spoke at length of Yousef’s life ...
(Date:11/29/2018)... ... November 29, 2018 , ... RAGS, today announced the ... Kickstart Seed Fund, with participation from existing investor and board member Jeremy Andrus, CEO ... of Cotopaxi. The additional funding will enable the company to accelerate its growth and ...
(Date:11/26/2018)... ... November 26, 2018 , ... USARAD Holdings ... and Omphalos Venture Partners (Virtual Radiologic founders) among other healthcare investors exhibits at ... at McCormick Place in Chicago. The company is proud to announce a 10 ...
(Date:11/20/2018)... ... ... Each year Forbes receives thousands of nominations for candidates wishing to be ... under 30 years of age. The Forbes 30 Under 30 list showcases the top ... Capital and Science. , In 2017, Visikol CEO Dr. Michael Johnson was named ...
Breaking Biology Technology: