Gene Knock Out Technology Knocks Out Malaria Parasite Channel

While performing animal tests, scientists have been able to prevent the malaria parasites from forming in mosquitoes by disrupting the potassium channel of the malaria parasite, thereby being successful in breaking the cycle of infection.

A research team consisting of scientists at the University of Copenha-gen and John Hopkins University, Baltimore, has genetically altered the malaria parasite through gene knock-out technol-ogy, thus preventing the parasite from going through the normal stages of its life cycle and developing a cyst (egg-like structure or occyst), which spawns new infectious parasites.

"As it is exclusively the parasites from these oocysts that can infect new individu-als, we were able to prevent the disease from being transmitted to the animals in our tests", explained Assistant Professor, Peter Ellekvist from the University of Copenhagen.

The malarial parasites have a complex life cycle, starting with the fertilisation of the parasites male and female gametes and the formation of an oocyst, in the mosquito's stomach wall. The oocyst further develops into sporozoittes, which travel up the mosquito's salivary gland and then get transmitted to people, when the mosquito secures its next blood meal. They first reside for a short period in the liver cells, and then infect the red blood cells, thereby wreaking havoc in the human body.

As the malarial parasites can reproduce both through sexual reproduction when they inhabit a mosquito (and are transmitted to the host) and via asexual reproduction when they reside in the human body (replication in the host), the scientists have to deal with both types of transmission to successfully counteract malaria.

All animal and plant cells contain so-called ion channels. These are small pores, which allow ions to move in and out through an otherwise impermeable cell membrane. The potassium channels are a sub-type of ion channel, found in all cells, and play a crucial role in many biological processes, e.g. influencing the ability of the nerves to send electrical signals and the heart muscle to contract rhythmically.

Ellekvist explained that his interest in malaria led him to collaborate with Professor Dan Klærke, who studies potassium channels at the University of Copenhagen and other researchers. Then they were able to manipulate the parasite's genes for ensuring that the potassium channel no longer functioned. Surprisingly, this intervention did not, in the first instance, appear to have any effect on the parasites.

"The gene knock-out parasites essentially killed the mice in the animal tests just as quickly as the "natural" parasites, that had not undergone genetic manipulation. However, we found that the only parasites that were unable to reproduce sexually, were those with non-functioning potassium channels," he explained.

The experiments had effectively disrupted the insect's ability to pass on the disease.

The researchers are now planning to examine whether parasites with non-functioning potassium channels react differently to anti-malaria drugs. If successful, this would allow the researchers to break the second phase of the infection cycle and prevent the asexual reproduction of the malaria parasites that have already gained access to the human body.

The findings have been published in the scientific journal Proceedings of the National Academy of Sciences, USA.

Source-ANI
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