Understanding how malaria parasites become resistant to drugs

Malaria parasites cause approximately 240 million infections each year, which results in approximately 608,000 deaths annually. There are drugs that help treat malaria infection and the current best treatments are artemisinin-based combination therapies.

Unfortunately, parasites are developing resistance to artemisinin. It is known that specific mutations in the Kelch-13 gene underpin artemisinin resistance phenotypes and one specific mutation in this gene, C580Y, has been linked with treatment failure throughout Southeast Asia.

Most of the global malaria disease burden is experienced by West Africa, where fortunately artemisinin resistance is not yet widespread and artemisinin-combination therapies remain effective treatment options.

Alarmingly however, novel African-specific mutations in Kelch-13 are being detected in East Africa and are expected to spread to West Africa in the next 5-7 years. As these mutations are different from those that have been well-defined in Southeast Asia, it is not yet known what effect they will have on artemisinin resistance.

This project will seek to understand how these novel mutations will affect malaria parasites from West Africa. It will involve inserting these point mutations into the Kelch-13 gene into parasites of Africa origin and assessing if they engender artemisinin resistance.

This project will involve state-of-the-art molecular biology techniques with a variety of plate- and microscopy-based phenotypic assays. It will have a real-world impact as it will help predict the effect of these mutations in currently circulating parasite populations.