The Vector Molecular Biology Unit focuses on the molecular aspects of salivary and midgut transcripts and proteins in vector/host and vector/parasite interactions. We are interested in the use of salivary genes as vaccines to block parasite or pathogen transmission and in the use of midgut proteins as transmission blocking vaccines. We have previously identified and isolated a salivary gene from the sand fly Phlebotomus papatasi that confers protection against Leishmania major infection in mice. The approach to use vector salivary proteins or genes to block parasite infection may be applicable to other species of Leishmania and also to other vector borne diseases. By using high-throughput approaches we have isolated and sequenced a large number of cDNAs from various species of sand flies and from the tick Ixodes scapularis, the vector of Lyme disease. We have selected a number of these salivary genes and prepared DNA vaccines using a high-throughput cloning approach. We tested salivary DNA constructs from the sand flies P. argentipes, P. ariasi and L. longipalpis in animals and identified salivary proteins that produced a strong delayed skin response, salivary proteins that produce a strong antibody response and salivary proteins that produced both types of immune responses. Future work is directed to test these molecules for protection against pathogen transmission and to understand the mechanism of this protection. Another interest of the unit is the identification of the Leishmania major attachment site on the Phlebotomus papatasi sand fly midgut. Classical biochemical attempts have failed to identify and isolate this attachment site in the vector midgut. We have isolated and sequenced a large set of full-length genes expressed on the midgut of P. papatasi and identified a transcript coding for a tandem repeat galectin (galactose binding protein) and named PpGalec. Confocal microscopy studies demonstrated that PpGalec is expressed in the midgut surface of P. papatasi. Invitro and invivo binding experiments show that PpGalec is used by Leishmania major as a receptor for mediating specific binding to the insect midgut, an event that is crucial for parasite survival and that accounts for species-specific vector competence. These studies demonstrate the feasibility of using midgut receptors for parasite ligands as target antigens for transmission-blocking vaccines.