Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene expands malaria’s invasion options

29.08.2005


The malaria parasite Plasmodium falciparum uses different pathways to invade red blood cells, evading the body’s immune system and complicating efforts to create effective vaccines against the disease. A research team led by Australia’s Alan F. Cowman, an international research scholar with the Howard Hughes Medical Institute, has identified a gene that the parasite uses to switch back and forth between invasion pathways.



Researchers from the Scripps Research Institute in La Jolla, California, and the Genomics Institute of the Novartis Research Foundation in San Diego contributed to the work, which was published in the August 26, 2005, issue of Science, P. falciparum causes the most lethal form of malaria, which results in one million deaths a year worldwide.

Some P. falciparum strains invade red blood cells via protein receptors on the surface that contain a sugar known as sialic acid. If scientists treat blood cells with an enzyme to remove sialic acid, the parasite can no longer invade. Other strains – including one called W2mef – can invade using the sialic acid receptors, but also have the ability to switch to other pathways if necessary.


"It’s a bit like someone trying to get into a house with different doors," says. Cowman of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and the study’s senior author. "When you remove sialic acid, you block half the doors. W2mef normally goes in through the receptors with sialic acid, but it can switch – so it has two methods of entry."

To investigate how the parasite manages to switch to an alternative mode of blood cell invasion, Cowman and colleagues produced lines of the W2mef parasite that used sialic acid for invasion, and lines that could invade without it. Then they compared the differences in gene activity between the two types and identified two genes that warranted further study.

The team found only two genes whose activity differed between parasites that used sialic acid and those that did not. The first of these was a gene known as P. falciparum reticulocyte-binding like homolog 4 (PfRh4) that’s similar to other genes known to play a role in the invasion of red blood cells by P. falciparum and related parasites. The second gene, EBA165, did not appear to produce a functional protein, and the scientists suspect it had been activated only because it was physically adjacent to PfRh4. Using a second, more quantitative approach, the team found that the two genes were 60- to-80 times more active in the sialic acid-independent parasites than in those that needed the sugar for cell entry.

These results suggested that activation of the PfRh4 gene was required for the parasite to make the switch to sialic acid-independent invasion. Indeed, the team was able to find PfRh4 protein in sialic acid-independent parasites, but not in the sialic acid-dependent lines. And when the group constructed parasites in which the PfRh4 gene was disrupted, they found that those parasites would not grow in the absence of sialic acid, although they grew normally on cells with the sugar – further suggesting that activation of the PfRh4 gene is required for switching from sialic acid-dependent to –independent invasion.

"Activation of PfRh4 represents a previously unknown mechanism to switch invasion pathways and provides P. falciparum with exquisite adaptability in the face of receptor changes and immune system responses," the team concluded.

The results have important implications for the design of anti-malaria vaccines. The molecule on the parasite that binds to sialic acid receptors on host cells is considered a target in anti-malaria medications, but Cowman notes that if only that gene is blocked, some parasites can still use PfRh4 to switch to other means of entry. "If both genes are disrupted, it blocks both ways of getting in," he says.

Brad Allen | EurekAlert!
Further information:
http://www.researchaustralia.com.au/
http://www.wehi.edu.au

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

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...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>