Researchers from Seattle Biomedical Research Institute (Seattle BioMed), the University of Copenhagen and the University of Edinburgh have uncovered new knowledge related to host-parasite interaction in severe malaria, concerning how malaria parasites are able to bind to cells in the brain and cause cerebral malaria – the most lethal form of the disease.
Three related papers will be published in the May 21 online edition of PNAS (Proceedings of the National Academy of Sciences), a premier scientific journal, highlighting this research.
"Identifying the molecules that allow malaria parasites to 'stick' to the brain takes us one step closer to new treatments," said Joseph Smith, Ph.D., leader of the Seattle team.
Red blood cells infected with the malaria parasite Plasmodium falciparum, the type most lethal to humans, bind to receptors on cells lining blood vessel walls, which helps the parasite avoid being detected and killed by the spleen. The binding is mediated by one of several members of a family of parasite proteins called P. falciparum erythrocyte membrane protein 1, or PfEMP1. A single PfEMP1 mediates placental malaria – the cause of malaria during pregnancy, which kills thousands of women and causes premature births and low-birth weight babies each year – but other PfEMP1 types causing life-threatening disease in young children are unknown.
To hone in on specific PfEMP1 types associated with severe malaria, Thomas Lavstsen, Ph.D., and his team from the University of Denmark used molecular techniques to compare the levels of different PfEMP1 transcripts in blood samples from children hospitalized in the pediatric ward of the Korogwe District Hospital in Tanzania. "Our research revealed that genes encoding two distinct types of PfEMP1 - named domain cassettes 8 and 13 - were tied to cases of severe malaria, suggesting that those proteins might be suitable targets in efforts aimed at curbing the disease," explained Lavstsen. Co-author Louise Turner, Ph.D. adds "Another important aspect of our study is that we show these PfEMP1 domain cassettes are recognized by natural acquired immunity in young African children, which gives us hope that we can base a vaccine on the discovered PfEMP1 types."
In a related paper in this issue, Antoine Claessens, Ph.D., who works in the lab of Alexandra Rowe, D. Phil., of the University of Edinburgh, reports that these particular PfEMP1 types – domain cassettes 8 and 13 – mediate the binding of infected red blood cells to cells that line blood vessels in the brain. "This provides us with new molecules that could be targeted to develop drugs to treat the most deadly forms of malaria," said Rowe. "In addition, because animal models for cerebral malaria are currently unavailable, we believe our findings might lead to a laboratory tool for testing drugs and vaccines that block the binding of the parasite to blood vessels in the brain."
Marion Avril, Ph.D., who works in the Smith lab at Seattle BioMed, reports in this issue that domain cassette 8 encodes binding activity for brain blood vessel cells. Additionally, the authors uncovered a potential explanation for the evolutionary persistence of parasite protein variants that mediate cerebral malaria, an often-fatal disease that tends to wipe out the parasite's host.
"Because those brain-binding variants can also bind to blood vessels in the skin, heart, and lung, the parasite might sequester in those organs," Smith explained. "Together, the findings could help researchers better address the lingering problem of childhood malaria."
"It's been a 15-year journey since this gene family was discovered, but the coming together of these three studies, which all identify the same key players in severe malaria, is an important milestone," said Rowe. "We're excited to have this knowledge and begin to apply it to developing new solutions for malaria."ABOUT SEATTLE BIOMEDICAL RESEARCH INSTITUTE:
For more information, contact:Lee Schoentrup, Communications Director
3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg
Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology