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

Tropical Medicine Section
Chairman’s Summary
The Tropical Medicine Section at present combines the
Departments of Molecular Medicine and Pathology as
well as the Kumasi Centre for Collaborative Research in
Tropical Medicine (KCCR), a joint research centre of
the Bernhard Nocht Institute with the University of Kumasi,
Ghana. The Section used to include a Bioinformatics
Group, which was discontinued in September
2002 when its head, Bertram Müller-Myhsok, accepted
an offer for a professorship at the Max Planck Institute
for Psychiatry, Munich. At present, collaborative
arrangements are being evaluated with the newly established
interdisciplinary Centre for Bioinformatics and
with the Institute of Medical Biometrics and Epidemiology
of Hamburg University in order to define the needs
of an own research group.
Most of the activities of the Department of Molecular
Medicine were concentrated to support projects at
KCCR aimed at characterizing thousands of individuals
for genetic studies on the susceptibility to malaria and
pulmonary tuberculosis. Several hundreds of siblings
were longitudinally monitored for malaria parasitaemias
and mild clinical malaria. In addition, thousands of
cases of severe and complicated malaria and pulmonary
tuberculosis were enrolled in hospital-based
studies, and, in parallel, parents and matched-pair controls
were recruited by mobile teams.
Laboratory work in Hamburg included DNA extractions
of thousands of samples from the extended enrolments
of study participants in Ghana, the typing of
short-tandem-repeat markers in the human genome for
linkage analyses and of single-nucleotide polymorphisms
for association studies of candidate gens. Ongoing
genotypings address established and novel candidate
genes.
A genome-wide linkage analysis and subsequent
gene identification revealed an important influence of
variants in the interferon-γ receptor on the course
of Helicobacter-pylori infection in a Senegalese study
population.
An ongoing survey on Familial Mediterranean Fever,
which is based on a selected service activity of genetic
diagnostics, has revealed several novel mutations of the
Mediterranean-fever gene and has enabled a first evaluation
of clinical data collected through patient questionnaires.
Studies on congenital hearing impairment in
Africa were continued by linkage analyses of extended
pedigrees characterized in a collaborative project with
the University of Gezira, Wad Medani, in Sudan.
The associated group of Norbert Brattig complements
the genetic studies of the department by providing
immunological expertise for a detailed characterization
of study subjects. Thus, phenotyping for filarial infections
was refined by studying the responses of peripheral
blood lymphocytes to filarial antigens, and proj-
Tropical Medicine Section
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ects have been started to characterize renal dysfunction
and cardiac impairment in malaria. The group
continued its work on the molecular biology of filarial
proteases and immune activation by Wolbachia endosymbionts.
Recent work of the Pathology Department and its
international collaborators continued to address fundamental
studies on the mechanisms of immunoprotection
by an attenuated SIV strain used for vaccination in
the monkey model of HIV/AIDS. Protection was found
associated with a substantial expansion of bone marrow-derived
mature dendritic cells and of T lymphocytes
of the γδ subset at the site of viral entry. Interestingly, in
contrast to the naïve controls, no evidence was obtained
for an expansion of cytotoxic lymphocytes in the
vaccinated and challenged macaques. A smaller
project of the department addresses the role of
macrophages and dendritic cells in the pathology of
Buruli ulcer. Another large grant coordinated by Paul
Racz has been secured from the European Union to further
study HIV vaccination strategies.
The Bioinformatics Group used its outstanding
methodological expertise in genetic epidemiology and
computational biology to contribute to several institute
projects on infectious diseases such as amoebiasis,
onchocerciasis, Helicobacter-pylori infection and a
mouse model of American trypanosomiasis. The group
also was engaged in a number of outside collaborations
addressing the genetic epidemiology of lipid
metabolism and neurological disorders.
The Kumasi Centre for Collaborative Research in
Tropical Medicine (KCCR) hosts extended research
programmes on malaria, filariasis and tuberculosis and
smaller studies on Buruli ulcer, aflatoxin ingestion, congenital
deafness and HIV infection. The projects are
summarized separately in this issue. Due to considerable
external funding obtained from the European
Union, the German initiative on malaria and the German
Genome Research Network, the Centre maintained its
high level of activities.
Rolf Horstmann