The broad objectives of our program have been the characterization of polypeptides which may have physiological and immunological importance for the establishment and survival of malaria parasites in their hosts. The know protein (KP) of Plasmodium falciparum interacts with the host erythrocyte membrane and induces membrane protrusions called knobs. These protrusions are essential for the survival of this parasite in the host. The objectives of this project are: (1) To identify the structural domain(s) of the KP of one isolate of P. falciparum which are involved in the induction of knobs. (2) To determine whether these domains are conserved in other geographical isolates as well as in a different species of malaria which induces knobs and (3) To determine whether these domains are immunogenic in man. To achieve these objectives, KP and its peptides will be expressed in yeast and E. coli. The expressed polypeptides will be tested for reactivity with specific cytoskeletal proteins of the host erythrocyte membrane and with immune human sera. The conserved sequences of KP will be identified by analysis of the KP gene of different geographical isolates of P. falciparum and that of Plasmodium brasilianum.