Max Planck Institute of Molecular Physiology

Max Planck Institute of Molecular Physiology

In line with its scientific mission, "from molecule to man", the Max Planck Institute of Molecular Physiology conducts basic biomedical research in Dortmund. At the interface between structural biology, molecular cell biology and chemical biology, the Institute’s scientists pursue an interdisciplinary research approach leading to a unique liaison between chemistry and biology. The scientific concept aims to achieve a holistic understanding of the dynamics of cellular reaction networks. By identifying and synthesising near-natural active substances, the scientists can accurately modulate intracellular processes. State of the art imaging methods are used to depict molecular reactions in cells. An important aspect of the scientists' systems-biological research work is the act of clarifying the molecular causes of diseases which, as in the case of cancer, are based on faulty intracellular signal transmission.

Contact

Otto-Hahn-Str. 11
44227 Dortmund
Phone: +49 231 133-0
Fax: +49 231 133-2699

PhD opportunities

This institute has an International Max Planck Research School (IMPRS):
IMPRS in Chemical and Molecular Biology

In addition, there is the possibility of individual doctoral research. Please contact the directors or research group leaders at the Institute.

Scientists model a crucial component of cell division
Researchers synthesize kinetochore and analyze the way it functions more
Why is Usain Bolt the fastest person on Earth?
Max Planck researchers observe muscles at work with the help of new microscopes more
Sharper than living matter permits
Max Planck researchers outsmart the biological uncertainty principle more
Nature’s pharmacy – plant-based active substance kills renal cancer cells
Extracted from the Phyllanthus engleri tree, englerin A kills the cancer cells by increasing their calcium concentration more
Scientists decode the three-dimensional structure of the calcium channel with unprecedented accuracy more
A cancer protein’s journey to cell membrane
KRas moves between various membranes within the cell, so that it is available in a sufficient quantity at its actual destination more
Toxic injection with elastic band

Toxic injection with elastic band

News February 24, 2014
Scientists discover how Tc toxins inject bacterial toxins more
New inhibitor blocks the oncogenic protein KRAS
Deltarasin prevents the transport of the oncogenic protein KRAS to the cell membrane more
Bacteria with vuvuzelas

Bacteria with vuvuzelas

News March 20, 2013
Microbes use a channel protein as a syringe for toxins more
Locating muscle proteins

Locating muscle proteins

News July 20, 2012
Max Planck scientists bring the basis of muscle movement into sharper focus more
New details about gene regulation explained
The transcription factor P-TEFb regulates RNA polymerase based on an unexpected pattern more
The German-Japanese Riken Max Planck Joint Research Centre for Systems Chemical Biology is taking shape
Kick-off symposium at the Max Planck Institute of Molecular Physiology in Dortmund from 5th to 7th March more
Biology-oriented synthesis (BIOS) – cancer drugs based on natural models
Max Planck researchers develop methods to simplify the search for effective substances and their synthesis more
Researchers generate Centrocountins involved in cell division in twelve-step cascade synthesis process more
Protein reveals oxygen availability to plants
Life span of RAP2.12 increases under hypoxia more
Bacteria, plants and animals are full of unknown substances that could be beneficial for humans. At the Max Planck Institute of Molecular Physiology in Dortmund, Herbert Waldmann tests natural products for their biological efficacy and tries to mimic their effects with simpler molecules.
In movies, 3-D effects are spectacular. And also at the Max Planck Institute of Molecular Physiology in Dortmund, Stefan Raunser finds that three-dimensional images offer a visual feast. His electron microscopes enable him to determine the position of individual atoms with great precision and to study the spatial structure of proteins. In doing so, he occasionally encounters some bizarre constructions.

Lost in Transcription

MPR 4 /2010 Biology & Medicine
How does HIV get a host cell to produce viruses? Researchers are looking for the key in order to develop efficient therapies.
2 Postdoctoral Positions
Max Planck Institute of Molecular Physiology, Dortmund September 08, 2017

High throughput drug discovery

2017 Sievers, Sonja; Waldmann, Herbert
Cell Biology Structural Biology
Small molecules interact with cellular components and thereby influence biological processes. In order to facilitate and accelerate the discovery of bioactive small molecules, an infrastructure for the storage and screening of small molecules was installed at the Compound Management and Screening Center (COMAS). The COMAS is an important mile stone in the Max Planck-Society`s exploitation of Know-How for medical research and the development of new pharmaceutical applications. more

How to control chromosome segregation in mitosis: the kinetochore at the heart of the check point

2016 Basilico, Federica; Breit, Claudia; Keller, Jenny; Klare, Kerstin; Krenn, Veronica; Maffini, Stefano; Overlack, Katharina; Petrovic, Arsen; Primorac, Ivana; Weir, John; Musacchio, Andrea
Cell Biology Structural Biology
During cell division, from each chromosome, the carriers of a cell's genome, identical copies are made in the mother cell. These are later transmitted to the two daughter cells in a process called chromosome “segregation”. Chromosome segregation requires specialized structures named kinetochores, which are established on a specialized region of each chromosome named the centromere. Kinetochores are multi-protein assemblies, and they are required to connect the chromosomes to a dynamic structure, the mitotic spindle, whose main function is to separate the replicated chromosomes. more

Elucidation of autophagy using novel chemical probes

2015 Wu, Yaowen
Cell Biology Chemistry Physiology Structural Biology
Autophagy is an important self-eating process in cells to eliminate or recycle cellular components or proteins out of use and takes place in cell organelles called autophagosomes. Development of autophagosome membranes involves complicated assemblies of lipids and proteins, highly regulated by a network of signals. Chemical probes including chemically modified proteins and small molecules enable researchers to elucidate the regulation mechanism of autophagy and molecular basis of autophagosome formation, previously not possible using traditional biochemical and cell biological approaches. more

Bacterial nano syringes

2014 Gatsogiannis, Christos; Raunser, Stefan
Cell Biology Chemistry Physiology Structural Biology

Bacteria use different strategies to manipulate and infect their host. Researchers at the MPI of Molecular Physiology were able to reveal a novel mechanism by which the Tc toxins of the bacterium Photorhabdus luminescens attack insect cells. An exceptional molecular cocoon containing a deadly component and a unique nano syringe play important parts in this mechanism. The new findings are critical to understand the transport of these toxic cargoes through membranes and serve as a strong foundation for the development of medical applications.

more

Targeting oncogenic Ras action

2014 Papke, Björn
Cell Biology Chemistry Physiology Structural Biology

Gene mutations in our genetic makeup are the major cause of cancer. A gene mutated in one out of three tumors is the Ras gene. Last year scientists at the Max Planck Institute of Molecular Physiology developed a new molecule which targets oncogenic Ras dependent tumors. Instead of focusing on Ras directly, the new molecule targets an interaction partner of Ras that is responsible for its localization within the cell. Inhibition of this interaction partner changes the localization of Ras, and hereby inactivates oncogenic growth signaling.

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How computer aided experiments light up cells to enlighten us

2013 Schmick, Malte
Cell Biology Physiology
Intracellular signaling pathways reacting to outside influences decide the fate of cells. These pathways are constructed from convoluted networks of interactions amongst proteins, the properties of which define those interactions, but conversely are continuously changed by these interactions. Computer aided modeling of the dynamics of the proteins involved allows the researcher to monitor the emerging patterns in the macroscopic behavior of cells stemming from these molecular scale interactions. more

Hunting for the ideal synthesis

2013 Antonchick, Andrey P.
Chemistry

The development of novel efficient synthetic methods is a subject of great importance. Scientists of the MPI for Molecular Physiology describe new approaches for the rapid access to chemical entries. Those methods are based on mild, metal-free and environment benign processes.

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Learning from pathogenic microorganisms

2012 Itzen, Aymelt; Hedberg, Christian
Cell Biology Medicine Microbiology
Transport processes in human cells are essential for various cellular activities, e.g. the destruction of disease agents. Therefore, a class of switch proteins direct the temporal and spatial coordination of intracellular transportation. Some pathogens (e.g. the causative agent of Legionnaires’ disease) have contrived ways and means to manipulate these processes. The investigation of the molecular basis of such manipulations enables researchers to develop a deeper understanding of the biochemistry of diseases but also of the principles of intracellular transport processes. more

Mitosis or the process of division of cells and chromosomes

2012 Musacchio, Andrea
Cell Biology Medicine Structural Biology
After DNA replication, chromosomes consist of two identical copies of the genetic material “glued” together. During mitosis, or M-phase, the “glued” chromosomes (sister chromatids) align on a scaffold known as the mitotic spindle. Upon completion of alignment, the sister chromatids become separated and distributed to opposite ends of the dividing mother cell. This way, each daughter cell inherits an equal complement of chromosomes. Problems in the execution of mitosis lead to unbalances in chromosome numbers (aneuploidy), a common genetic abnormality in tumors. more

A tug-of-war in nerve cells: How does the complex form of neurons develop?

2011 Dehmelt, Leif; Mazel, Tomáš; Arens, Julia; Zimmermann, Silke
Cell Biology Neurosciences Physiology
The structure and function of the brain develops from numerous shape changes, movements and specializations of cells. Changes in the shape of cells are primarily induced via fibrous proteins of the so-called cytoskeleton. These fibrous proteins are shifted by molecular motors, producing forces inside cells. The complex shape of the principal cell type of the brain, the neuron, is generated by concerted interactions of such forces. The emergence of global patterns from fluctuations of independent agents via self-organization plays an important role in this process. more

Development of chemical probes in proteases research

2010 Kaiser, Markus; Clerc, Jérôme; Hauske, Patrick; Mönig, Timon; Krahn, Daniel
Chemistry Material Sciences Solid State Research
Proteases are involved in countless biological processes. The application of selective small molecules for studying the biological function and regulation of proteases represents a promising alternative to established methods such as knock-out approaches. Here the development of such chemical tools from natural products and by rational design is reported with emphasis on progress in the application of the natural product syringolin as a proteasome inhibitor and the development of small molecule probes for HtrA proteases. more

Bioactive peptide natural compounds in chemical biology

2009 Arndt, Hans-Dieter; Baumann, Sascha; Lu, Jin-Yong; Riedrich, Matthias; Schoof, Sebastian
Chemistry Medicine
Peptide natural products are structurally related small molecules which occur in nature and display broad biological activity. Scientists at the Max Planck Institute in Dortmund focused on thiopeptides and on chondramide C, potent antibiotics and an F-actin addressing cytostatic. Progress in elucidating their molecular mode of action, in designing derived fluorescent probes and in access by chemical synthesis is reported. more

Regulation of transcription is an interface between cell growth and HIV stimulated gene expression

2008 Schulte, Antje; Czudnochowski, Nadine; Schönichen, André; Geyer, Matthias
Genetics
The transcription of chromosomal DNA into messenger RNA (mRNA) is a central process of eukaryotic gene expression. Shortly after initiation, transcription is paused by inhibition of the positive transcription elongation factor P-TEFb. This arrest acts as a control step before productive elongation of mature mRNA molecules takes place. P-TEFb is regulated by the protein Hexim1 and the small nuclear RNA 7SK. Scientists from MPI of Molecular Physiology in Dortmund have analysed the interaction between P-TEFb and its regulatory factors on a molecular level and shown, how the HIV Tat protein relieves this arrest to stimulate gene expression and production of viral proteins. more

Novel proteins for the activation of molecular switches in plants

2007 Berken, Antje; Fricke, Inka; Scrima, Andrea; Thomas, Christoph; Weyand, Michael; Wittinghofer, Alfred
Cell Biology Plant Research
Rho-proteins act as molecular switches that regulate vital processes in eucaryotic organisms. Their activation is essential for the processing of multiple internal and external stimuli. Scientists at the MPI in Dortmund recently discovered the responsible activating proteins in plants, which apparently represent the direct link to signal perceiving cell surface receptors. Although these proteins differ significantly from their analogues in animals and fungi, they still follow a general reaction mechanism. more

The Biosynthesis of Phenazines

2006 Ahuja, Ekta G.; Bayer, Peter; Blankenfeldt, Wulf; Janning, Petra; Herde, Petra; Mavrodi, Dmitri V.; Thomashow, Linda S.
Chemistry Microbiology
Phenazines are nitrogen-containing aromatic compounds with antibiotic properties that many bacteria synthesize and secrete into their environment to defend themselves against other competing microorganisms. Phenazine biosynthesis branches off the shikimate pathway but details remain elusive. Scientists from the MPI for molecular physiology have demonstrated that PhzF, a conserved enzyme of the bacterial phenazine biosynthesis operon, isomerises 2,3-dihydro-3-hydroxo anthranilic acid to a ketone. This product dimerises and subsequently undergoes several oxidation and a decarboxylation reaction to yield phenazine-1-carboxylic acid, the end product of the pathway. Using an approach that involves structural and biochemical methods, scientists in Dortmund have obtained evidence for the catalytic role of each of the enzymes of the phz-operon and are able to generate an almost complete structural and mechanistic picture of this interesting pathway. more

Structural Classification of Ligand Binding Protein Cores and Natural Products as Guiding Principles for Chemical Genomics

2006 Koch, Markus; Wetzel, Stefan; Waldmann, Herbert
Chemistry Computer Science Structural Biology
For the development of small molecules for chemical biology and medicinal chemistry research relevance in nature is the decisive criterion. For the identification of biologically relevant and prevalidated starting points in vast structural space for compound collection development structural similarities in the ligand sensing cores of proteins and in their natural ligands, i. e the small natural products emerging by biosynthesis, are identified. This analysis is used for similarity clustering of proteins and structural classification of natural products. This approach at the MPI for Molecular Physiology leads to hypothesis-generating tools setting the starting points for chemical genomics research, i. e. the identification and use of small molecules to elucidate the biological function of protein families. more

Structure and Molecular Mechanisms of Clock Proteins

2005 Berndt, Alex; Breitkreuz, Helena; Hennig, Sven; Köster, Stefan; Schulze, Sabrina; Theiss, Christiane; Wolf, Eva; Yildiz, Özkan; Wittinghofer, Alfred
Cell Biology Neurosciences Structural Biology
Most organisms exhibit day-time dependent activity cycles, referred to as circadian rhythms, which are generated and synchronized with the environmental light-dark cycle by internal biological clocks. By structurally and biochemically characterizing the clock protein PERIOD of the fruit fly Drosophila, scientists at the Max Planck Institute in Dortmund were able to obtain important insights into animal clock mechanisms. Biological, biochemical and biophysical experiments proposed by this X-ray crystal structure will assist in delineating the molecular mechanisms underlying the human circadian clockwork. more
This report details the increase in knowledge on the basic mechanisms in sugar absorption in the intestine and reabsorption in the kidney. It describes how the biophysical principles of cell asymmetry and asymmetry of the transport molecules are realized at the molecular level and how the problems of transport selectivity and transport energetics are solved by specific subdomains of the transporter. Thereby a complex series of events is described which in the end leads to the vectorial transport of sugars across the membrane and across the cell. The report also illustrates how the combination of the most modern techniques from different areas of Life Sciences is essential for the progress, this transdisciplinary research is one of the highlights of the research conducted at the Max Planck Institute in Dortmund. more

New Methods for the Combinatorial Solid Phase Synthesis of Compound Libraries

2004 Breinbauer, Rolf; Gonthier, Elisabeth; Nad, Sukanya; Köhn, Maja; Niemeyer, Christof; Peters, Carsten; Waldmann, Herbert
Chemistry
The development of Organic Synthesis on Solid Phase (SPOS) allows the fabrication of a diverse set of organic molecules in a short time, which can function as potential ligands in biological screens. The scientists from MPI in Dortmund have been successful in implementing electroorganic reactions on solid phase, which adds a new class of reaction type to the methodological toolbox of SPOS. In addition they have established a new method for the fabrication of small molecule arrays which can be used in biological high-throughput-screening. more

Structural and mechanistic aspects of intracellular vesicular transport regulation

2004 Alexandrov, Kirill; Durek, Thomas; Goody, Roger S.; Niculae, Anca; Pylypenko, Olena; Rak, Alexey; Schlichting, Ilme; Reents, Reinhard (Abt. 4); Waldmann, Herbert (Abt. 4); Watzke, Anja (Abt. 4)
Cell Biology Chemistry Structural Biology
The integrity of eukaryotic cells depends on their ability to maintain an array of dynamic membrane bound intracellular structures such as endosomes, lysosomes, Golgi apparatus etc. These organelles communicate with each other and the cellular environment via shuttling transport vesicles in a process known as intracellular vesicular transport. This process is governed by GTPases of the Rab family that function as molecular switches controlling events of vesicular transport, docking and fusion. In order to perform their function RabGTPases have to associate with cell membranes via covalently attached lipid moieties. This modification, which is conferred posttranslationally by the multisubunit enzyme Rab geranylgeranyl transferase (RabGGTase) enables Rab proteins to interact with membranes and other regulatory proteins such as Rab GDP dissociation inhibitor (RabGDI). Mutations interfering with either Rab prenylation or Rab:GDI interaction are known to lead to a number of pathologic conditions in humans. Scientists from MPI for Molecular Physiology have used a combination of protein semi-synthesis, kinetic analysis and X-ray crystallography to elucidate the structure and function of RabGGTase subunits and RabGDI in complex with Rab GTPases. Based on these data they provide a mechanistic model for human choroideremia disease and non-syndromic mental retardation. more
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