Grant: Project Grant

Malaria is one of the greatest threats to human health today. Globally, there are approximately 200 million cases per year, resulting in approximately 600,000 deaths, the majority of which are small children. Malaria is caused by a microscopic parasite transmitted from mosquitoes to human hosts. Once inside the host, the parasite invades red blood cells to consume nutrients from the host in order to develop and multiply. The treatment, control, and eradication of malaria have long been impeded by the ability of the parasite to rapidly develop resistance to antimalarial drugs. Therefore, it is imperative to develop new drugs that act through molecular mechanisms distinct from existing drugs to control the disease and combat the spread of drug resistance. Due to the complex biochemical interactions between the drug, parasite, and human host, identification of the molecular target of potential antimalarial drugs is an enormous challenge requiring years of intense research. An emerging approach for identifying the molecular target of antimalarials is to sequence the genome of parasites that have developed drug resistance in order to identify the responsible genetic mutations. This project aims to develop a new technology to isolate these drug-resistant parasites in order to sequence their genome to rapidly identify the molecular target of antimalarial drugs. This work leverages a recent discovery made by our research team that found all antimalarial drugs dramatically reduce the deformability of infected red blood cells, which aids the clearance of the infected cells from the host. Using this characteristic, our technology will separate infected red blood cells based on mechanical deformability in order to isolate cells drug-resistant parasites from those containing drug-sensitive parasites. Once separated, we will then sequence the genome of mutated parasites in order to identify the molecular target of potential antimalarial drugs.