Research Group Heussler (Malaria I) - Bernhard-Nocht-Institut für ...

Parasitology Section
Chairman´s Summary
The Parasitology Section constitutes the largest section
of the institute. It combines the Department of Molecular
Parasitology, the Department of Biochemistry and a
number of research groups, working on various parasites
of medical importance. Emphasis was given to
amoebiasis, leishmaniasis and malaria, three parasitic
diseases with high impact on morbidity and mortality
in most tropical and subtropical countries (selected
projects are described in the following reports).
Work on amoebiasis was performed in the Department
of Molecular Parasitology. As part of an international
consortium to sequence the Entamoeba histolytica
genome, members of the department have participated
in various projects. These included the analysis of RNA
splicing, genetic comparisons between E. histolytica
and the closely related but nonpathogenic species
E. dispar, and characterization of cysteine proteinases.
The latter constitutes a major pathogenicity factor,
which is responsible for the extraordinary high capacity
of E. histolytica to destroy human tissues. Interestingly,
the E. histolytica genome was found to contain at least
30 different cysteine proteinase genes, some of which
are absent in E. dispar (Iris Bruchhaus). In addition to
genomic research, comprehensive studies on the
epidemiology and treatment of E. histolytica infections
have been performed in close collaboration with the
Medical College and the Central Hospital in Hué, Vietnam.
These activities led to new recommendations on
the treatment of amoebiasis (Jörg Blessmann). Moreover,
work has been continued on the development of
an amoebiasis vaccine. On the basis of gram negative
bacteria expressing E. histolytica antigens via the type
III secretion pathway, an oral vaccine was generated,
which was able to confer a considerable degree of
protection against amoebic liver abscess in laboratory
animals (Hannelore Lotter).
Various groups of the Parasitology Section have
participated in Leishmania research. Iris Bruchhaus and
co-workers performed a comprehensive proteome analysis
in order to follow changes in the protein profile during
Leishmania stage conversion from the extracellular
promastigote form present in the insect vector to the
amastigote form present in human macrophages. The
group of Joachim Clos has applied functional genetics
to identify several genes that have an impact on the
species-specific tropism of Leishmania spp. Using the
same strategy, genes responsible for drug resistance of
L. donovani and L. infantum were isolated. In addition,
a novel L. donovani gene was found that governs reentry
into the cell cycle after growth arrest and suppresses
virulence in vivo. The group of Martin Wiese
has concentrated on Leishmania signal transduction
pathways. They identified nine mitogen-activated pro-
Parasitology Section
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tein (MAP) kinase genes in L. mexicana indicating that
these evolutionary early divergent parasites use similar
signal transduction mechanisms as higher eukaryotes.
Moreover, a MAP kinase kinase homologue was identified,
which is involved in flagellar assembly and length
control. The potential of the encoded proteins as drug
targets to treat leishmaniasis is currently investigated.
During the last few years malaria research has expanded
within the institute and is currently being performed
in all three sections. Within the Parasitology
Section work was continued on polyamine metabolism.
Using genetic approaches as well as higly selective inhibitors,
it was shown that the bifunctional enzyme
ornithine-S-adenosylmethionine-decarboxylase of
Plasmodium falciparum is essential for parasite growth,
suggesting that the enzyme might constitute an excellent
target for antiparasitic drugs (Rolf D. Walter). Another
target, the glutathion-s-transferase of P. falciparum
was characterized by high resolution structural analysis
allowing the construction of more specific inhibitors
(Eva Liebau). Survival of intracellular parasites depends
on their ability to circumvent apoptosis of the host cell.
Using the rodent parasite P. berghei as a model system
Volker Heussler and co-workers investigated survival
strategies of Plasmodium parasites in hepatocytes from
entry of sporozoites to the release of merozoites. In
course of their ongoing studies they could show that
during the first two days of infection the parasite protects
host cells from apoptosis, whereas it induces
apoptosis on the third day followed by the release of
merozoites. The process of Plasmodia host cell invasion
involves an array of proteins located in specialized exocytic
organelles of the parasite. These proteins are involved
in recognition, adhesion, and active invasion of
host cells. Using knock-out technology, the newly established
group headed by Tim Gilberger will focus on
two aspects of P. falciparum erythrocyte invasion: (i)
Identification and characterization of new determinants
of cell invasion and (ii) protein trafficking and sorting
of proteins to their subcellular location.
Apart from protozoan research, field studies
were performed to characterize insect vectors that
are responsible for onchocerciasis transmission in
South-Tanzania. This work will clarify whether vector
control in addition to drug treatment is more suitable
for onchocerciasis eradication in this endemic area
(Andreas Krüger).
The two service units located within the Parasitology
Section, the Electron Microscopy Unit and the DNA
Sequencing Unit have proven to be of great help for
many of the research groups, which is documented
by the large number of investigations that have been
performed in the two units.
Egbert Tannich