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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI019845-07
Application #
3565464
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1982-09-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Public Health Research Institute
Department
Type
DUNS #
City
Newark
State
NJ
Country
United States
Zip Code
07103
Kilejian, A; Rashid, M A; Aikawa, M et al. (1991) Selective association of a fragment of the knob protein with spectrin, actin and the red cell membrane. Mol Biochem Parasitol 44:175-81
Kilejian, A; Rashid, M A; Parra, M et al. (1991) Sequence of the knob protein of Plasmodium falciparum recognized by a monoclonal antibody. Mol Biochem Parasitol 48:231-3
Rashid, M A; Yang, Y F; Kilejian, A (1990) Expression, partial purification and immunogenicity of fragments of the knob protein of Plasmodium falciparum. Mol Biochem Parasitol 38:49-55
Kilejian, A; Yang, Y F; Cochrane, A H et al. (1990) Homologous sequences in Plasmodium cynomolgi and the gene of the histidine-rich knob protein of Plasmodium falciparum. Mol Biochem Parasitol 38:291-3
Tan-Ariya, P; Yang, Y F; Kilejian, A (1988) Plasmodium falciparum: comparison of the genomic organization of the knob protein gene in knobby and knobless variants. Exp Parasitol 67:129-36
Yang, Y F; Tan-ariya, P; Sharma, Y D et al. (1987) The primary structure of a Plasmodium falciparum polypeptide related to heat shock proteins. Mol Biochem Parasitol 26:61-7
Sharma, Y D; Kilejian, A (1987) Structure of the knob protein (KP) gene of Plasmodium falciparum. Mol Biochem Parasitol 26:11-6
Kilejian, A; Sharma, Y D; Karoui, H et al. (1986) Histidine-rich domain of the knob protein of the human malaria parasite Plasmodium falciparum. Proc Natl Acad Sci U S A 83:7938-41
Kilejian, A; Chen, S; Sloma, A (1985) The biosynthesis of the histidine-rich protein of Plasmodium lophurae and the cloning of its gene in Escherichia coli. Mol Biochem Parasitol 14:1-10
Kilejian, A; Rosenbaum, S (1985) Reactivity of a monoclonal antibody produced to the histidine-rich protein of Plasmodium lophurae with Plasmodium falciparum. Mol Biochem Parasitol 17:155-62