Malaria causes a tremendous amount of global suffering. More than 500 million people become ill with malaria every year and more than 1 million die. Most of these deaths are in young children under the age of five. Most severe malaria is caused by a parasite called Plasmodium falciparum. New drugs are urgently needed for malaria, because the parasite has become resistant to drugs that have been commonly used, such as chloroquine. This project examines the route by which the malaria parasite generates isoprenoids (called the “DXP pathway”). Isoprenoids are a group of compounds that have many important jobs within the cell, and disruption of this pathway will probably kill the parasite. This DXP pathway is a particularly attractive drug target, because humans make isoprenoids by a completely separate route. Drugs that target the parasite pathway should not be harmful to people. The goals of this project are to understand better the genetic and biochemical roles of isoprenoids in the malaria parasite. Specifically, two of the genes of this pathway will be disrupted, in order to determine their effects on parasite development. Secondly, we will purify two of the enzymes of the pathway, and optimize them for future high-throughput screening of small molecule compound libraries to identify inhibitors. Enzyme inhibitors discovered in this way are expected to be good leads for future antimalarial treatments. This project will further our basic understanding of one of the most serious pediatric infections and also represents the first steps toward much-needed new antimalarial drugs.