David A. Spiegel of Yale University in the U.S. will pursue an antibiotic strategy called “biosynthetic immunotargeting.” Streptococcus pneumoniae will be fed small molecules which they will incorporate into their cell walls. These small molecules contain an epitope recognized by antibodies in the human bloodstream, leading to immune clearance independent of bacterial antigens, representing a unique, resistance-free approach to pneumococcal disease.

Manoj Duraisingh of the Harvard School of Public Health in the U.S. will use RNAi screening to identify critical determinants in human red blood cells (erythrocytes) that are required for invasion and growth of the malaria parasite, Plasmodium falciparum. In this project's Phase I research, Duraisingh's group developed a RNAi- based approach for genetic analysis of the erythrocyte in vitro, and demonstrated that the major surface protein Glycophorin A is required for efficient invasion by some strains of P. falciparum. The group made progress in the development of a high-throughput RNAi screen, which in Phase II of the project Duraisingh hopes will identify those essential erythrocyte determinants that are most amenable to the development of host-targeted drug therapies.

T. brucei, the parasite that causes sleeping sickness, must continuously swim forward in human blood to evade immune responses. Arthur Günzl of the University of Connecticut Health Center in the U.S. will attempt to develop serum-stable RNA molecules to immobilize the parasite by interrupting the mechanism driving parasite motility.

Anders Hakansson of the University of Buffalo in the U.S. has identified a protein from human breast milk (Human Alpha Lactalbumin Made Lethal to Tumor cell, or HAMLET), that kills respiratory tract bacteria. Hakansson will attempt to understand the mechanism by which HAMLET binds to and kills pheumococci without the bacteria developing resistance.