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Within the process of reorganization
of the Institute the former sections Parasitology and Molecular Biology
were combined. During the period of this report, various research groups
of the section participated in the institute research programs Amoebiasis
and Onchocerciasis and continued their ongoing research addressing topics
of pathogenicity, immunology, immunodiagnosis, immunolocalization, transmission
and the identification of vaccine and drug target candidates. Highlights
of activities in these fields are summarized separately by the program
coordinators in this annual report.
Within the Parasitology Section
malaria and leishmaniasis have become important research topics during
the past years. By applying reverse genetics, the Leishmaniasis Unit demonstrated
the role of a Leishmania major heat shock protein, Hsp 100, as a
virulence factor and selectable genetic marker during experimental infections
of mice. The homologous protein from L. donovani was shown to play
a pivotal role for the survival of this parasite in isolated mouse macrophages
and for amastigote-specific gene expression. These results will allow a
molecular analysis of stage differentiation in Leishmania parasites.
With the aim of anti-malaria drug
development members of the Biochemical Parasitology Unit continued studies
on the redox-state of Plasmodium falciparum-infected erythrocytes,
focusing on the glutathione and thioredoxin systems. The thioredoxin reductase
from P. falciparum, a member of a recently discovered novel class
of enzymes, was analyzed and by using site-directed mutagenesis techniques
the essential amino acids at the catalytic site of the enzyme were identified.
Further, the gamma-glutamylcysteine synthetase from P. falciparum
which catalyses the limiting step in the biosynthesis of glutathione, was
cloned, characterized and its potential as a target for rational drug design
was assessed. In addition, the studies on the classification of microsporidia
and on the improvement of the diagnosis of microsporidia infections were
continued, as well as the investigation of the polyproteinallergens of
nematodes, identified as fatty acid binding proteins. In order to investigate
parasite responses to the host immune attack and to identify genes that
are differentially expressed under oxidative stress condition, the model
nematode Caenorhabditis elegans was stressed and analyzed by differential
display techniques, which revealed increased levels of mRNAs for antioxidative
enzymes, transcription factors and various other genes.
Additional topics addressed by other
research groups of the section concentrated on deciphering mechanisms of
immunoregulation by characterizing the role of individual members of the
factor H gene family during immune evasion and by identifying the function
of transcription factors during a directed immune response of T lymphocytes.
Further, the mechanism of folding of integral membrane proteins was investigated
with the prototypic member bacteriorhodopsin. By using expressed polypeptide
fragments it was demonstrated that multihelical membrane receptors can
be refolded and assembled from several independent domains.
| Staff
Prof. Dr. Rolf D. Walter,
Visiting Scientists
Doctoral Students
Graduate Students
Support Staff
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Life Cycle of the Microsporidium Encephalitozoon |
