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During the period covered by this report, the
research groups in the Parasitology Section have continued their ongoing
research projects focusing on onchocerciasis, leishmaniasis and malaria.
The section was reduced by the Malaria Unit of Privatdozent K. Lingelbach,
who accepted a professorship for parasitology at the University of Marburg.
In addition, Prof. R. Garms a well-known Simulium researcher retired, but
he will continue his work as an associate member of the institute.
The figure shows Leishmania major parasites after in vitro infection of isolated mouse macrophages. Two days p.i. wild type L. major parasites already show proliferation inside the macrophages (A). In contrast, a L. major Dclpb mutant which is deficient in expression of the 100 kDa heat shock protein (Hsp 100) has entered the macrophages but does not proliferate (B). |
The Leishmaniasis Unit has been successful in identifying
a gene crucial for the differentiation and development of Leishmania in
the early stages of an infection, a finding which constitutes the first
bona fide evidence for the long proposed role of the heat shock response
for the survival of parasites within the mammalian host. The gene encodes
a 100 kDa heat shock protein which is synthesized in the intracellular
amastigote stage of the parasite. The essential function of this protein
was demonstrated by reverse genetics. The disruption of the gene in Leishmania
major led to a markedly reduced virulence which is probably due to an impaired
promastigote to amastigote differentiation early in the course of the infection.
Members of the Division of Helminthology and Entomology continued field studies in Western Uganda focused upon onchocerciasis and other filarial infections. Infection with the filarial parasite Mansonella streptocerca was detected, characterized and treated with ivermectin. In order to obtain a better understanding of the epidemiology of onchocerciasis in this region and possibilities for vector control, the biting range of Simulium neavei was analysed. Furthermore, to identify those cytotypes of S. damnosum s.l. and S. neavei which feed on man and are potential vectors of Onchocerca volvulus, morphological, biochemical and molecular biological parameters were developed to distinguish these forms. In continuation of former immunohistological studies on O. volvulus and in order to establish comparative immunological and vaccine studies with model infections, the distribution, frequency and activity of mast cells, granulocytes and macrophages found in the vicinity of various Onchocerca species in animal tissues were studied. Also, in collaboration with other groups, various enzymes from O. volvulus were localized by immunohistochemical and immuno-electron microscopical methods in order to obtain a better insight into their function in the parasite-host interaction. With the aim of assessing potential targets in the metabolism of O. volvulus and Plasmodium falciparum for rational antiparasitic drug design and to identify vaccine candidates, members of the Biochemical Parasitology Unit have analysed the polyamine metabolism as well as investigated key enzymes involved in the maintenance of the thiol redox-state and the antioxidative defense. Evidence was provided that the extracellular form of the superoxide dismutase is a secreted enzyme and may play a role in the interactive biology of O. volvulus with their host. In addition, a disulfide reductase recently cloned from P. falciparum was identified as thioredoxin reductase and was analysed with respect to kinetic properties and structural differences, as a prerequisite for the design of specific inhibitors. The production of recombinant S-adenosylmethionine decarboxylase from O. volvulus and the collaboration with the pharmaceutical industry allowed the testing of various compounds, designed as inhibitors of this enzyme, in order to identify chemical leads for drug development. Further, methods for the diagnosis of microsporidia infections were established to fill the needs of the increased medical importance of this protozoan infection, not only for patients with im- mune suppression but also for those infected with tropical diseases. Rolf D. Walter
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| For additional information please also see Investigators’ Reports. |
| Staff
Prof. Dr. Rolf D. Walter, Chairman from April, 1996, and Head, Biochemical
Parasitology
Dr. Iris Ansorge
Visiting Scientists A. S. Mahmoud, Onchocerciasis Chemotherapy Research Centre, Hohoe, Ghana
Doctoral Students Sven Brandau
Graduate Students Cornelia Hoyer
Support Staff Ingeborg Albrecht
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