08/04/05

Gene study unmasks the many faces of malaria

Malaria parasite invading a red blood cell Copyright: Wellcome Trust / A.J. Knell

By: Mike Shanahan

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<div class="article-wrap">
<div id="article-introduction">
<h1>Gene study unmasks the many faces of malaria</h1>
<h4>By: Mike Shanahan</h4>
</div>
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<div id="article-body">
<p><P>Scientists have discovered the genetic basis of the game of ‘hide and seek’ the malaria parasite plays with the human immune system.</P><br />
<P>The research, published today in the journal <em>Cell</em>, could open the door to new drugs against <em>Plasmodium falciparum</em>, the most deadly form of the malaria parasite.</P><br />
<P>When the parasite enters human cells, one of its proteins appears on the outside of the cell. This would normally give the immune system a target to aim at in order to destroy infected cells. </P><br />
<P>But by the time the immune system has produced antibodies that recognise the malaria protein, the parasite is already one step ahead, presenting a different form of the protein that the antibodies cannot recognise.</P><br />
<P>The parasite is a master of disguise, constantly changing the version of the protein to avoid being detected.</P><br />
<P>Researchers have known for about a decade that a family of at least 50 malaria genes known as ‘var’ genes are responsible for this ability. They are activated one at a time to produce different forms of the protein. The mechanism the parasite uses has, however, been elusive.</P><br />
<P>Now, a team led by Alan Cowman and Brendan Crabb at The Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, has shown that the parasite varies the protein by ‘silencing’ some of its genes.</P><br />
<P>It does this by producing other proteins that wrap tightly around its own DNA, blocking and deactivating the var genes.</P><br />
<P>The researchers showed that one of the proteins involved is called SIR2. When they modified the parasite to stop making SIR2, more of its var genes remained active.</P><br />
<P>According to Cowman, forcing the parasite to turn all of the var genes on would allow the human immune system to ‘see’ all variations of the protein that the parasite produces on the surface of infected cells. This would enable the body to fight infection.</P><br />
<P>The research suggests that drugs targeting the method malaria uses to hide its var genes could make the parasite vulnerable to the immune system.</P><br />
<P>However, the researchers add that SIR2 is only part of the puzzle, and that more research will be needed to determine what other factors control how many var genes are active at one time.</P><br />
<P><a  href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSN-4FWM4P4-6&_coverDate=04%2F08%2F2005&_alid=264776289&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=7051&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=00f3c554039cca18dc8844b04f259e76" target="_blank" onclick="pageTracker._trackPageview('/tracking/external/'+this.href);" rel="noopener noreferrer">Link to abstract of paper in <EM>Cell</EM></A><BR><BR>Reference: <em>Cell</em> 121, 13 (2005)</P></p>

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Scientists have discovered the genetic basis of the game of ‘hide and seek’ the malaria parasite plays with the human immune system.

The research, published today in the journal Cell, could open the door to new drugs against Plasmodium falciparum, the most deadly form of the malaria parasite.

When the parasite enters human cells, one of its proteins appears on the outside of the cell. This would normally give the immune system a target to aim at in order to destroy infected cells.

But by the time the immune system has produced antibodies that recognise the malaria protein, the parasite is already one step ahead, presenting a different form of the protein that the antibodies cannot recognise.

The parasite is a master of disguise, constantly changing the version of the protein to avoid being detected.

Researchers have known for about a decade that a family of at least 50 malaria genes known as ‘var’ genes are responsible for this ability. They are activated one at a time to produce different forms of the protein. The mechanism the parasite uses has, however, been elusive.

Now, a team led by Alan Cowman and Brendan Crabb at The Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, has shown that the parasite varies the protein by ‘silencing’ some of its genes.

It does this by producing other proteins that wrap tightly around its own DNA, blocking and deactivating the var genes.

The researchers showed that one of the proteins involved is called SIR2. When they modified the parasite to stop making SIR2, more of its var genes remained active.

According to Cowman, forcing the parasite to turn all of the var genes on would allow the human immune system to ‘see’ all variations of the protein that the parasite produces on the surface of infected cells. This would enable the body to fight infection.

The research suggests that drugs targeting the method malaria uses to hide its var genes could make the parasite vulnerable to the immune system.

However, the researchers add that SIR2 is only part of the puzzle, and that more research will be needed to determine what other factors control how many var genes are active at one time.

Link to abstract of paper in Cell

Reference: Cell 121, 13 (2005)