Eradicating malaria is difficult partially because the transmission cycle is complex with multiple different stages that occur inside mosquitos after consuming a blood meal from humans. Compounds that could kill the parasite or block transmission in the mosquito during early stages of parasite maturation would be ideal. A recent study describes how our reporter enzyme NanoLuc® luciferase was combined with a Plasmodium parasite and used to create a model to identify drug compounds that block malarial transmission during the stage where male and female reproductive cells are fertilized.
Expression and activity of the luciferase gene in this mutant strain is controlled by an element that responds only to the sexual states of the parasite. When the parasite was just circulating in the blood, there was little bioluminescence. When the parasite converted into the cells that form a zygote like the stage in a mosquito, the amount of bioluminescence increased, suggesting that NanoLuc® luciferase was only expressed when these reproductive cells developed.
This NanoLuc® malaria strain called Ookluc was used to test compounds in the Pathogen Box from the Medicines for Malaria Venture. This research kit contains 400 compounds that are active against neglected tropical diseases—125 of the compounds are known to target malaria. Researchers found 31 compounds that blocked over 95% of the reporter parasite conversion into the reproductive cells, preventing the early reproductive stage. These results suggested the NanoLuc® luciferase-based Ookluc model is ideal for high-throughput screening of compounds that block malaria transmission. Thus, we are one step closer to identifying possible drugs that may eradicate malaria.
Fulfilling the Needs of Government and Academic Research Laboratories
Despite increasing pressure and demands, today’s academic and government researchers are still at the front line of discovery but require more sensitive research tools to test their hypotheses. They need the newest available tools with enhanced sensitivity and specificity to address more complex biological questions compared to the methods used just a few years ago. From routine applications to more focused ones, Promega continues to develop these improved technologies from next generation nucleic acid isolation and PCR, to advanced assays for cellular biology, metabolism, 3D cellular structures and organoids, to protein manipulation and CRISPR knock-ins for tagging cell lines. To help the modern researcher successfully publish their results, fulfill their research programs and nurture carefully planned careers, Promega is committed to developing the most advanced bioassays, target engagement and protein degradation tools. Promega values people, and we understand that every researcher is an individual with their own stresses and strains.