Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Reveal Malaria's Deadly Grip

06.06.2013
Researchers at the University of Copenhagen, in collaboration with Seattle Biomedical Research Institute, the University of Oxford, NIMR Tanzania and Retrogenix LTD, have identified how malaria parasites growing inside red blood cells stick to the sides of blood vessels in severe cases of malaria. The discovery may advance the development of vaccines or drugs to combat severe malaria by stopping the parasites attaching to blood vessels.

Though researchers have known for over a century that red blood cells infected with malaria parasites can kill their host by sticking to the sides of blood vessels, the binding mechanism associated with the most lethal forms of malaria was unknown.

Now, in a study published in Nature, the researchers show that the parasite binds a protein in blood vessel walls called endothelial protein C (EPCR), which is involved with regulating blood coagulation and the inflammatory response.

Malaria parasites grow in red blood cells and stick to the endothelial lining of blood vessels through a large family of parasite proteins called PfEMP1. This way, the parasite avoids being carried with the blood to the spleen, where it would otherwise be destroyed. One of the most aggressive forms of malaria parasite binds in brain blood vessels, causing a disease called cerebral malaria. In 2012, three groups of researchers, including the teams at the University of Copenhagen and Seattle Biomedical Research Institute, showed that a specific type of PfEMP1 protein was responsible for cerebral binding and other severe forms of malaria infection. However, until now, the receptor to which it binds remained unknown, and the next big question was to determine which receptors the infected red blood cells were binding to.

“The first big challenge was to generate a full-length PfEMP1 protein in the laboratory,” says Assistant Professor Louise Turner at the University of Copenhagen. “Next, we utilized a new technology developed by Retrogenix LTD in the United Kingdom to examine which of over 2,500 human proteins this PfEMP1 protein could bind to.” Of the 2,500 proteins screened, a receptor called endothelial protein C (EPCR) was the single solid hit.

“A lot of work then went into confirming this binding in the lab and not least to show that parasites from non-immune children with severe malaria symptoms in Tanzania often bound EPCR,” she continues.

“It was a true eureka moment,” says Assistant Professor Thomas Lavstsen. “Under normal conditions, ECPR plays a crucial role in regulating blood clotting, inflammation, cell death and the permeability of blood vessels. The discovery that parasites bind and interfere with this receptor´s normal function may help us explain why severe symptoms of malaria develop."

Malaria parasites disrupt the important functions of blood vessels
Severe malaria symptoms such as cerebral malaria often result in minor blood clots in the brain. One of our body´s responses to malaria infection is to produce inflammatory cytokines, but too much inflammation is dangerous, describes Professor Joseph Smith, from the Seattle Biomedical Research Institute. “ECPR and a factor in the blood called protein C act as a ‘brake’ on blood coagulation and endothelial cell inflammation and also enhance the viability and integrity of blood vessels, but when the malaria parasites use PfEMP1 to bind EPCR, they may interfere with the normal function of EPCR, and thus the binding can be the catalyst for the violent reaction,” he explains.

“Investigating this question is the next step to learn about how malaria parasites cause disease.”

Towards an intervention
The discovery that malaria parasites bind EPCR may advance vaccine and drug interventions to treat severe malaria. Dr. Matthew Higgins from the University of Oxford explains:

“Now that we know the pair of proteins involved, we can begin zooming further in to reveal the molecular details of how malaria parasites grab onto the sides of blood vessels. We want to know exactly which bits of the parasite protein are needed to bind to the receptor in the blood vessel wall. Then, we can aim to design vaccines or drugs to prevent this binding.”

Vaccine research will also benefit immediately from the discovery, since scientists can already now test the effectiveness of different vaccine candidates at preventing PfEMP1 from binding ECPR. “Over the last decade, we have come to appreciate that specific PfEMP1 proteins are associated with different severe forms of malaria,” explains Professor Thor Theander at the University of Copenhagen. “Together with The National Institute for Medical Research Tanzania, we are in the process of preparing phase I trials for a vaccine to prevent parasite binding in the placenta and malaria during pregnancy,” he explains. This new discovery holds the potential for also developing a vaccine to reduce the heavy burden malaria disease inflicts on children. “It will be a long haul, but with these results, we can get started right away,” he says.

ABOUT SEATTLE BIOMEDICAL RESEARCH INSTITUTE:
Seattle BioMed is the largest independent, non-profit organization in the U.S. focused solely on infectious disease research. Our research is the foundation for new drugs, vaccines and diagnostics that benefit those who need our help most: the 14 million who will otherwise die each year from infectious diseases, including malaria, HIV/AIDS and tuberculosis. Founded in 1976, Seattle BioMed has more than 330 staff members. By partnering with key collaborators around the globe, we strive to make discoveries that will save lives sooner. For more information, visit www.seattlebiomed.org.

Hannah Krakauer | Newswise
Further information:
http://www.seattlebiomed.org

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

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

Hubble captures massive dead disk galaxy that challenges theories of galaxy evolution

22.06.2017 | Physics and Astronomy

New femto-camera with quadrillion fractions of a second resolution

22.06.2017 | Physics and Astronomy

Rice U. chemists create 3-D printed graphene foam

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>