Therapeutics/Drugs

Jean-Laurent Casanova of The Rockefeller University in the U.S. seeks to identify single gene mutations that are critical to immunity against bacterial infections. By characterizing these mutations, Casanova could provide insight into a genetic basis for the susceptibility of some children to Tuberculosis, that could inform a recombinant IFN-y drug therapy.

Filippo Mancia of Columbia University in the U.S. will perform crystallization experiments on a key olfactory receptor used by mosquitoes to detect humans. The aim of these studies is to determine at an atomic level the conserved regions on the olfactory receptor in order to develop drug therapies to block these receptors. This project's Phase I research generated diffraction quality crystals of this targeted mosquito olfactory receptor, and in Phase II, the team will optimize the crystal to determine the structure of the receptor and how it binds to small molecule anti-malarial compounds.

Todd Sulchek of Georgia Tech and David White of the Centers for Disease Control in the U.S. will develop and test the ability of a bi-functional microbead to stimulate the innate immune response. On one hemisphere, the microbead will display targeting antibodies that will bind to pathogens, and on the other hemisphere the microbead will feature Fc fragments that activate the complement system and recruit immune cells to destroy the captured pathogen.

Jun Zhu and Mark Goulian of the University of Pennsylvania in the U.S. propose to use phage display technology to engineer a commensal "sentinel" bacteria that be introduced into the gut flora. Bacterial toxins would be detected by the sentinel commensal, which would bind to the toxin and express enzymes to destroy it.

Christine Hrycyna and Jean Chmielewski of Purdue University in the U.S. will develop novel dimeric drugs designed to block a key protein in the malaria parasite that limits the accumulation of anti-malarials in the parasite's digestive system. By inhibiting this protein, this new therapy could eliminate drug resistance in malaria parasites.

Julie Dunning Hotopp of University of Maryland in the U.S. seeks to identify genes that have been laterally transferred into filarial nematode worm genomes from Wolbachia. Identifying these genes, could provide drug targets to cure neglected tropical diseases such as lymphatic filariasis and river blindness.

Robert H. Broyles of The Sickle Cell Cure Foundation, Inc. in the U.S. will build on the recent discovery that elevated fetal hemoglobin (HbF), which alleviates sickle cell disease, can also confer malaria resistance. Broyles will test the ability of a stable human protein to reactivate a silent gene that encodes for HbF, makings red blood cells inhospitable to malaria parasites. If successful, the idea is to target the therapy in the host to reduce malaria infections.

John Jaenike of the University of Rochester in the U.S. will test the hypothesis that infecting blackflies with the bacteria Spiroplasma could impair the ability to transmit the parasite responsible for River Blindness,and also increase fertility of female flies that can pass along this beneficial bacteria to its offspring.

HIV destroys helper T cells, which are essential to activation of B-cells. Irvin Chen of UCLA in the U.S. will utilize inducible pluripotent stem cell technology to generate a constant, self-renewing source of antigen-specific B-cells, which target conserved HIV epitopes to eliminate HIV-infected cells.

Antibodies and the complement system work together to specifically detect and clear viruses, but they are circumvented by HIV, which hides itself and the cells it infects by hijacking host proteins such as CD59. Qigui Yu of Indiana University School of Medicine in U.S. will attempt to unmask HIV and HIV-infected cells and render them susceptible to antibody-complement attack. In this project's Phase I research, Yu and his team identified a potent, specific, and non-toxic inhibitor of human CD59, which is used by HIV to escape destruction by antibody-complement attack.