Carbohydrates and carbohydrate-binding proteins not only inhibit parasite attachment to the midgut brush border but completely block parasite development as well. Since the identity of the full range of polypeptide backbones that can bear these glycans is unknown, specific protein targeting is unfeasible. However, it is known that addition of specific glycans to polypeptides, such as mucins and other gut glycoproteins are regulated by a defined family of resident transferases in the gut Golgi. We hypothesize that ookinete attachment can be reduced or completely inhibited by interrupting glycosylation of midgut lumenal glycoproteins. To test this hypothesis, we envision a two-step process: 1) molecular identification and biochemical characterization of mosquito midgut enzymes involved in the glycosylation of midgut brush border glycoproteins, and 2) the use of reverse genetics (RNAi gene silencing) to assess the functional role of selected midgut-specific glycosylation enzymes on Plasmodium infection. This line of experimentation will open up new avenues of research through the basic, glycobiological analysis of the mosquito midgut biology. ? ? ?
