Many potential drug targets against malaria, shows parasite’s gene function study

Two-thirds of the malaria parasite’s genes are essential for its survival, which makes it possible for new antimalarial drug development against the parasite that is increasingly developing drug resistance.

Two-thirds of the malaria parasite’s genes are essential for its survival,which exposes it to many more potential drug targets, showed the first ever large-scale study of the parasite’s gene function.

Plasmodium parasites are ancient organisms and around half their genes have no similar genes (homologs ) in other organisms, making it difficult for scientists to find clues to their function. (Shutterstock)

The parasite has the largest proportion of essential genes found in any organism studied to date, said scientists from the Wellcome Trust Sanger Institute in the journal Cell, which makes it possible for new antimalarial drug development against the parasite that is increasingly developing drug resistance.

Half the world’s population lives in malaria-infested areas, with south Asia, south-east Asia and Africa the worst hit. In 2015, malaria sickened 212 million persons and caused 429,000 deaths, estimates the World Health Organisation.

Malaria infection occurs throughout the year in India, but peaks between July and October when the weather is warm and wet. In 2016, there were 1.09 million confirmed cases and 331 deaths from malaria, shows government data, but the actual numbers are likely to be higher as many cases don’t get reported.

The genetics of the parasite that causes malaria, Plasmodium, have been tricky to decipher. Plasmodium parasites are ancient organisms and around half their genes have no similar genes -- homologs -- in any other organism, making it difficult for scientists to find clues to their function.

Scientists studied the genes in one species of malaria, Plasmodium berghei, which were expressed in a single blood stage of its multi-stage life cycle.

Using a new method to decipher the function of the parasite’s genes, scientists switched off more than half of the genome (2,578 genes) and gave each knockout a unique DNA barcode.

Scientists then used a next generation genome sequencing technology to count those barcodes and measure the growth of each genetically-modified parasite.

If the switched-off gene was not essential, the parasite numbers shot up, but if it was essential, the parasite disappeared.

“This method can be used to build a deep understanding of many unknown aspects of malaria biology, and radically speed up our understanding of gene function and prioritisation of drug targets,” said Dr Oliver Billker, joint lead author from the UK’s Wellcome Trust Sanger Institute, which led the study.

The team showed that the malaria parasite can dispose of the genes that produce proteins that give away its presence to the host’s immune system. This poses problems for the development of malaria vaccines as the parasite can quickly alter its appearance to the human immune system, which results in the parasite building resistance to the vaccine.

“Our study found that below the surface the parasite is more of a Formula 1 race car than a clunky people carrier. The parasite is fine-tuned and retains the absolute essential genes needed for growth. This is both good and bad: the bad news is it can easily get rid of the genes behind the targets we are trying to design vaccines for, but the flip side is there are many more essential gene targets for new drugs than we previously thought,” said Dr Julian Rayner, joint lead author from the Wellcome Trust Sanger Institute.