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Transmission Zero team members create new method to screen malaria parasite genes within mosquitoes

(L-R) Dr. Chiamaka Valerie Ukegbu, Prof. George K. Christophides, and Dr. Dina Vlachou observe malaria-infected mosquitoes in the lab

Transmission Zero researchers have devised a novel way to concurrently track the function of thousands of malaria parasite genes within mosquitoes to identify new preventatives. The breakthrough has been published today in Cell Host and Microbe:

Malaria is still responsible for hundreds of thousands of deaths annually, and increasing parasite resistance to treatment alongside rising mosquito resistance to insecticides is compounding this severe global issue. The new technique developed by the team could facilitate identification of novel targets that are critical for parasite development in the mosquito.

Identifying such critical components of the parasite lifecycle within the mosquito has proved extremely challenging in the past. Often, approaches rely on mutating single genes at a time and observing the outcomes in a long, inefficient process. Complicating the issue further, malaria parasites undergo sexual reproduction within the mosquito vector, and therefore attempts to introduce such genetic mutations can prove challenging when this process offers a chance for a working copy of the gene to be re-introduced during reproduction, which could ‘rescue’ the phenotype.

To overcome this challenge, the research team led by Dr. Dina Vlachou and Professor George K. Christophides capitalised on their earlier finding that male genes remain largely inactive following reproduction. As Dr. Vlachou explains: “We generated batches of exclusively female mutated gametes, which we then crossed with normal male gametes, ensuring the persistence of introduced mutations in resulting mature parasites. In this proof-of-concept, we studied a small number of genes, but the approach can be scaled up to screen thousands of genes simultaneously.”

The technique has already been put into practise, identifying novel genes that are indeed essential for malaria transmission. The first author of the study, Dr. Chiamaka Valerie Ukegbu said: “Among these new genes, mutations in two impede parasite motility, preventing mosquito infection, while mutations in another two obstruct the formation of parasites capable of infecting humans. The latter pair of genes encode proteins situated in the crystalloid, an enigmatic organelle only present in mosquito-stage parasites.”

Professor Christophides added: “Our results confirm that the crystalloid is key to parasite development in the mosquito, pointing to it as an excellent target for impeding disease transmission from mosquitoes to humans.”

The team are delighted to share this technology, and envisage this development as a significant step forward to catalyse further discoveries relating to host-parasite interactions and malaria transmission.

To read more about this exciting development in malaria research, please check out the paper:

The study published in Cell Host and Microbe was funded by the Wellcome Trust and the Medical Research Council.

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