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Research Project
Sequence and expression analysis of Plasmodium falciparum var
genes and immunological and functional analysis of PfEMP1 in
naturally infected human blood samples
Third-party funded project
Project title Sequence and expression analysis of Plasmodium falciparum var genes and immunological and
functional analysis of PfEMP1 in naturally infected human blood samples
Principal Investigator(s) Beck, Hans-Peter;
Organisation / Research unit Swiss Tropical and Public Health Institute (Swiss TPH) / Molecular
Parasitology and Epidemiology (Beck)
Project start 01.10.2007
Probable end 30.09.2010
Status Completed
Adherence of infected red blood cells to blood capillaries are responsible for the majority of the observed
pathology in malaria. This is mediated by a parasite protein on the surface of the infected cell, called PfEMP1.
PfEMP1 is variable and encoded by a large number of genes in a given population. In this project we will study
the diversity of expressed genes coding for PfEMP1 (var genes) to test our hypothesis that only a limited
number of these genes are responsible for pathology. We will extent our studies to sequence larger fragments
of the molecule which until now was elusive due to its size. Using a targeting cloning and sequencing strategy,
we plan to specifically sequence only var genes but from a large number of patients. We will use this
sequence information to select synthetic peptides using an bioinformatics approach to test their immunological
recognition and binding capacity to selected molecules. Finally, we will study the fate of PfEMP1 from the
parasite’s cytosol through the parasitophorous vacuole into the red blood cell membrane. In this subproject we
are interested in potential interaction partners enabling the parasite to modify the host cell to such extend. We
hope that the information gained during this project will identify potential virulence factors (selected PfEMP1
molecules) with the option to use these as vaccine candidates. Furthermore, by studying the transport and
trafficking of this clinically important molecule through the cell we hope to identify structures and transporters
which might become targets for interventions. Understanding the limits of diversity and understanding the
molecular events which are necessary to transport PfEMP1 to the surface is of utmost importance. Because
PfEMP1 is essential for parasite survival in vivo, understanding this process in detail may open completely
new strategies for intervening with this devastating disease.
Keywords PLASMODIUM FALCIPARUM, MALARIA, sequence analysis, Microarray, PFEMP1, ANTIGENIC
VARIATION, TAR cloning, transfection, trafficking, VAR GENES
Financed by
Swiss National Science Foundation (SNSF)
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Published results
533284, Koepfli C; Müller I; Marfurt J; Goroti M; Sie A; Oa O; Genton B; Beck HP; Felger I;, Evaluation of
Plasmodium vivax genotyping markers for molecular monitoring in clinical trials, Journal of Infectious
Diseases, {\ifthenelse{\equal{Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)}{
}}{}{Publication: JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
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