FEB 25, 2015 10:27 AM PST

Novel Method to Suppress Malaria Parasite's Virulence Genes

WRITTEN BY: Judy O'Rourke
5 48 2398
Up to one million people -- mainly pregnant woman and young children -- are killed each year by the Plasmodium falciparum parasite, which causes the most devastating form of human malaria.

Researchers at the Hebrew University of Jerusalem have revealed the genetic trickery this deadly parasite deploys to escape attack by the human immune system. The parasite is known to replicate within the circulating blood of infected individuals and modify the surface of infected red blood cells. Its virulence comes from its impressive ability to hide from the immune system by selectively changing which surface proteins it displays.
Micrograph depicts a Plasmodium falciparum parasite microgametocyte
"We believe this breakthrough has exposed the tip of the iceberg in understanding how the deadliest malaria parasite regulates the selective expression of its genes, enabling it to evade the immune system," says professorRon Dzikowski, PhD, School of Medicine-IMRIC-Microbiology and Molecular Genetics. "Understanding the mechanisms by which the parasite evades immunity takes us closer to finding ways to either block this ability, or force the parasite to expose its entire antigenic repertoire and thus allow the human immune system to overcome the disease. Such findings can help pave the way for development of new therapies and vaccines for malaria."

This sophisticated game of hide-and-seek, which involves continually alternating the foreign molecules (antigens) that can trigger an immune response, is called antigenic variation. Previous research has shown that the antigens the parasite selectively displays are encoded by members of a gene family named var. The parasite tightly regulates the expression of these var genes so that only one is expressed at any given time, while the rest of the family is maintained silent.

Understanding this complex mechanism is essential to understanding how the deadly Plasmodium falciparum parasite evades the immune system. It is also more broadly important to science because the process by which cells can express a single gene while keeping alternative genes silent is one of the unsolved mysteries in the field of eukaryotic gene expression.

In research at the university's Faculty of Medicine, Dzikowski and his PhD student Inbar Amit-Avraham found that at the precise moment in the cell cycle when a specific var gene is active, corresponding RNA molecules (of a type called long noncoding RNA) are present. These long noncoding RNA (lncRNAs) molecules incorporate themselves into DNA structures, and determine how the parasite selects a single gene for expression while the rest of the family is kept silent.

In a series of genetic experiments in transgenic parasite lines, the researchers were able to activate silent var genes by expressing their specific lncRNAs molecules, thus demonstrating their functional role in var gene activation.

In a further development, the researchers collaborated with Eylon Yavin, PhD, at the Institute for Drug Research in the university's School of Pharmacy, to develop a novel way to interfere with these lncRNAs. They further showed that through this interference they could suppress the active var gene, erase the memory that regulates var expression, and induce switching towards expression of other var genes.

The research provides evidence that these lncRNAs molecules play a key role in regulating the genetic mechanisms enabling the deadly parasite to evade human immunity.

The study, titled "Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum," appears in the Proceedings of the National Academy of Sciences (PNAS Early Edition).

[Source: The Hebrew University of Jerusalem]
About the Author
  • Judy O'Rourke worked as a newspaper reporter before becoming chief editor of Clinical Lab Products magazine. As a freelance writer today, she is interested in finding the story behind the latest developments in medicine and science, and in learning what lies ahead.
You May Also Like
MAY 21, 2018
Microbiology
MAY 21, 2018
Common Antibacterial Chemical may Help Fight Lung Infections
New research has found when triclosan is used with another FDA-approved drug, it can help fight deadly illness.
JUN 19, 2018
Microbiology
JUN 19, 2018
The Impact of Antibiotics on Gut Microbes
Antibiotics had a dramatic impact on the microbes of the GI tract in a research model.
JUN 20, 2018
Immunology
JUN 20, 2018
Immune System Accidentally Allows Meningitis Brain Infection
Several immune cells help fungi infect the brain and cause meningitis when they should be doing the exact opposite. From the University of Sydney, research
JUL 04, 2018
Drug Discovery
JUL 04, 2018
Discovery of New Properties of an Anti-Tuberculosis Drug
  Investigators at the University of Otago found novel properties of a new anti-tuberculosis drug which may inspire more new drugs to treat tuberculos
JUL 17, 2018
Microbiology
JUL 17, 2018
Understanding how Microbes Will Accelerate Climate Change
As permafrost starts to thaw out, it's exposing untold numbers of new bacteria, which can spew out methane.
AUG 02, 2018
Genetics & Genomics
AUG 02, 2018
The Genetic Hotspots That Can Lead to Cancer
In some of our body's tissues, cells have to replicate many times. That introduces a chance for new genetic errors every time.
Loading Comments...