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| Hamburg,
Monday, 23 June 2003 |
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| Fighting Mycobacterium tuberculosis with structural proteomics |
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| Press
Release 23 June 2003 [PDF] [Deutsch] EMBL Hamburg and partners receive a 3.5 million Euro grant from the German Federal Ministry of Education and Research to combat TB.
Tuberculosis
is one of the deadliest threats to public health today. An
estimated two billion people are infected with Mycobacterium
tuberculosis [Mtb], with eight million new cases annually
and two million people dying from the infection each year.The
situation is further aggravated by the lethal alliance of
HIV and Mtb co-infection. HIV patients have weakened immune
systems, making them more susceptible to secondary infections
and about one-third of HIV patients die from tuberculosis.
The most effective Mtb-specific antibiotics were
developed more than thirty years ago, and since
that time, the bacterium has learned to defend
itself to become resistant to many of the current
drugs.The great need for effective drugs has led
researchers at the European Molecular Biology
Laboratory [EMBL] Hamburg Outstation and a mix
of academic and industrial collaborators to study
the proteins in the bacterium, which are the functional
machines behind the tuberculosis. By studying
the structures of these proteins, an approach
termed 'structural proteomics', they hope to find
more effective drugs against Mtb.
In support of their efforts, the German Federal Ministry of
Education and Research has now awarded a 3.5 million Euro
grant as part of the government's proteomics initiative "New
efficient procedures for functional proteome analysis". The
project will be coordinated by EMBL Hamburg and comprises
three additional academic partners [Max-Planck Groups for
Molecular Structural Biology, Hamburg; Max-Planck-Institute
for Infectious Biology, Berlin; Technical University of Munich,
Research Center Weihenstefan] and three industrial partners
[Biomax, Martinsried; Combinature, Berlin; MarResearch, Norderstedt].
EMBL Hamburg and their partners will work together to apply a step-by-step, structure-based
approach to this drug discovery oriented process. In a novel approach, the Max-Planck-Institute for
Infectious Biology, Berlin, will analyse the expression of Mtb proteins in infected lung material.Target
proteins from Mtb suitable for further analysis will be selected by the scientists from the Technical
University of Munich using bioinformatic tools.Their structures will then be solved by X-ray crystallography
using the synchrotron radiation beamlines in Hamburg, or by NMR spectroscopy in
Berlin. Using the structural data, researchers from the company Combinature and the Research
Center for Molecular Pharmacology will test these targets against a high number of potential druglike
compounds to see if any may 'stick' to the target proteins. If the function of these proteins can
be blocked, researchers may gain insight into how the bacterium causes disease. Promising targets
will be taken through future biological and pharmacological analysis.
Apart from providing more insight into the bacterium's proteins, this project will also enable the
partners to develop equipment and infrastructure. A key goal will be to implement a high-throughput
crystallization facility at EMBL Hamburg."This facility will be one-of-a-kind in Europe and will be
made available to the academic and industrial research community using high-throughput X-ray crystallography,"
notes Dr. Matthias Wilmanns, Head of the EMBL Hamburg Outstation." It will give
researchers the infrastructure that is needed to undertake major crystallography projects." In addition,
MarResearch GmbH will develop and implement automatic sample changer facilities that automate
and speed up the analysis of samples at state-of-the-art synchrotron radiation beamlines.Also,
Biomax AG will implement a central database, capable to cope with the large variety of data from
the different partners.
"The generous support from the German government will enable our scientists to take great leaps
forward in Mycobacterium tuberculosis research," comments Dr. Wilmanns, "We will be able to
make significant progress in this battle and be at the forefront of discovering new drugs against this
disease."
Scientific
Contact
Matthias Wilmanns
EMBL Hamburg, c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany
Tel: +49
[0] 4089 9020
Fax: +49
[0] 4089 902104
E-mail: wilmanns@embl-hamburg.de
Web page: www.embl-hamburg.de |
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