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
Researchers develop high-performance cancer vaccine using novel microcapsules
25.05.2020 | Chinese Academy of Sciences Headquarters
Blood flow recovers faster than brain in micro strokes
25.05.2020 | Rice University
Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.
When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...
Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.
Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...
Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.
A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...
By studying the chemical elements on Mars today -- including carbon and oxygen -- scientists can work backwards to piece together the history of a planet that once had the conditions necessary to support life.
Weaving this story, element by element, from roughly 140 million miles (225 million kilometers) away is a painstaking process. But scientists aren't the type...
Study co-led by Berkeley Lab reveals how wavelike plasmons could power up a new class of sensing and photochemical technologies at the nanoscale
Wavelike, collective oscillations of electrons known as "plasmons" are very important for determining the optical and electronic properties of metals.
19.05.2020 | Event News
07.04.2020 | Event News
06.04.2020 | Event News
25.05.2020 | Medical Engineering
25.05.2020 | Information Technology
25.05.2020 | Information Technology