The Max Planck Society initiates a new "Chemical Genomics Centre" at the crossroads of Biology, Chemistry and Medicine in
Dortmund -
While the field of genetics investigates and influences the life's processes by modifying the genes themselves, the field of
chemical genetics pursues this goal using chemical compounds that modulate the functioning of the gene and its products
(proteins, RNA, etc.). Therefore, chemists, biochemists and biologists from six Max Planck Institutes will work together in
the new "Chemical Genomics Centre" in Dortmund in the search for small molecules that allow the study of fundamental
life-science processes and the involved biological macromolecules. The Max Planck Society invests a total sum of 5 million
euro. The chemical compounds will be designed and made based on natural products analogues, via combinatorial chemistry or
rational design and their biological relevance will be tested subsequently in plants, animals and micro-organisms. In this
way, molecules shall be identified that are capable of targeting disease relevant proteins or that are candidates for crop
protection.
In the past decade it became increasingly clear that all biological processes in principal rely on chemical processes and are
governed by the structure of the participating molecules and their interactions. Biological processes can be treated as
chemical processes and studied in molecular detail. Nevertheless, up to today for only 500 of the over 100.00 proteins
encoded by the human genome a chemical compound is known that interacts with and influences the protein. Therefore research
following the sequencing of the genome is increasingly focussed on the function of its proteins and their interactions with
small molecules (modulators). A new approach for this is Chemical Genomics.
What is chemical genomics?
Chemical genomics uses drug-like molecules as modulating ligands for cell-biology research, to clarify for example the
function of a certain gene product. For a long time such probe-molecules were only found via serendipitous discoveries and
observations. Progress in the automation and parallelisation of chemical synthesis and biological analysis enables the
systematic search of modulators of protein function for the investigation of biological phenomena.
The research approach defined as "chemical genetics" (the study of individual gene products using a combination of chemical
and biological methods), and "chemical genomics" (the analogous study of the products of a gene family has certain advantages
over the genetic methods: The effects of small molecules are generally fast and reversible due to the metabolism and
excretion of the molecules. This enables the transient study of proteins. The effect is tuneable, as a varying concentration
can result in different degrees of phenotype expression. On top of that, the effect can be initiated and studied at different
stages in the development of the organism. Finally, the access to small molecule probes enables anyone to study the effect.
How to find molecular probes for chemical genetics?
Chemical genetics has as a goal to identify substances or molecules that bind with high affinity and specificity to one or a
few of the around 100.00 different proteins. Methods developed for combinatorial chemistry enable the synthesis of biological
potentially relevant libraries of chemical compounds. An additional source for molecular probes is the isolation or chemical
total synthesis of "natural compounds". These are generally complex molecules synthesized by animals or plants and have been
optimized for a specific purpose over a period of millions of years via an evolutionary process.
The molecular libraries will subsequently be tested in a variety of biological screens. In these automated tests the screens
are monitored via for example optical methods that determine morphological changes of the cells or of complete organisms.
Using fluorescence based methods it is possible to localize and quantify special optical markers. Once a substance with a
specific biological effect has been identified, it will be used as a starting point for the analysis of the effect and the
identification of the involved target protein. Using genome and proteome analysis, the influence of the protein or the active
substance on the complete cell will be investigated. With the generation of this knowledge, the substance can be used as a
tool for extensive biological studies and its therapeutic relevance can be evaluated. In the end, this may lead to the
substance becoming a "lead compound" for the development of new drugs.
Chemical genomics is a powerful new research approach for the fundamental biomedical research. In addition, the approach
promises to have a higher efficiency in the search for lead compounds for drug development, because it integrates chemistry
and biology already in an early stage in the research process. In this way it permits a fast identification of compounds with
high biological relevance.
The Chemical Genomics Centre (CGC) in Dortmund
The Max Planck Society endorses the new interdisciplinary research approach via the founding of an institute-overlapping
Chemical Genomics Centre (CGC). Participating institutes are the Max Planck Institute for Molecular Physiology, Dortmund, for
Molecular Cell Biology and Genetics, Dresden, for Coal Research, Mьlheim, for Plant Breeding Research, Kцln, for Psychiatry,
Mьnchen and the Max Planck Institute for Biochemistry, Martinsried. The design and synthesis of the biologically relevant
compound libraries based for instance will be pursued in Dortmund and Mьlheim. The biological screening and evaluation of the
developed molecular tools will be performed in Kцln for plants and in Dresden, Martinsried, Mьnchen and Dortmund for
mammalian cell lines.
"We are living in the "post genomics" age, which means that we know and have access to the complete genetic information of
not only humans, but also of model organism like the mouse and rat. Also, the genetic information present in important
nutrition plants like beans and rice is known. However, to make the promises of the genetics research reality, it is required
that biology and chemistry form an alliance", says Herbert Waldmann, director at the Max Planck Institute for Molecular
Physiology and coordinator for this multi-institute-spanning initiative of the Max Planck Society. "The CGC is currently the
most important research initiative in its field in Europe. Especially the participation of the pharmaceutical industry is
unique and enables research projects, normally not pursuable by universities or research institutes."
The build-up of the centre is endorsed by the Max Planck Society with a total of 5 million euro for an initial period of 5
years. This should enable the instalment of several junior research groups and support the research activities at the
participating institutes. Furthermore pharmaceutical companies will participate as funding and research partners, financing
additional research groups. All research groups will be hosted in the new labs of the Biomedical Centre Dortmund, in the
immediate vicinity of the Max Planck Institute for Molecular Physiology.
The research groups supported by the companies will perform basic research on new, currently not sufficiently explored, areas
for which, however, great potential for drug development is foreseeable. An example could be the pharmacologically oriented
investigation in the interactions between proteins involved in the signal transduction pathways in the cell, leading to new
approaches to modulate these interactions.
"The CGC creates a dynamic and inspiring research environment for all participants", states Herbert Waldmann. "Research will
start in the summer of 2005 and it is already predictable that this will lead to very interesting and possibly completely
unexpected results."
Related links:
[1] Website of the Chemical Genomics Centre
PDF (102 KB)
Contact:
Prof. Dr. Herbert Waldmann
Max Planck Institute of Molecular Physiology, Dortmund
Tel.: +49 231 133-2400
Fax: +49 231 133-2499
E-mail: herbert.waldmannmpi-dortmund.mpg
Dr. Peter Herter
Max Planck Institute of Molecular Physiology, Dortmund
Tel.: +49 231 133-2500
Fax: +49 231 133-2599
E-mail: peter.hertermpi-dortmund.mpg
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ISSN 0170-4656
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