Welcome to the MPI of Molecular Physiology

Every day the trillions of cells in our bodies ensure that we are able to see, think, speak and move. How does each cell ‘know’ what to do? How can an organism arise from millions of nanometer-sized molecules although there is no blueprint? What actually is ‘life’? For centuries, philosophers and natural scientists have been trying to solve this mystery. Many questions remain unresolved to this day.

We want to know how the building blocks of the cells organize themselves and ensure that certain chemical reactions occur at the right time in the right place – or how errors lead to the development of diseases like cancer. To achieve this, we are studying the relevant processes on multiple levels – from single molecules and larger protein complexes to whole cells.


Group photo
We congratulate the best biology A-level students of NRW, who were awarded the Karl-von-Frisch Prize by the VBIO at a ceremony at the MPI in Dortmund.
Where to put head and tail?
beta-Catenin discovered as a new key player in the formation of the main body axis during mammalian embryogenesis
Boehringer Ingelheim Foundation supports research of Peng Wu
Peng Wu receives ~1 million euros from the Boehringer Ingelheim Foundation for the development of novel RNA-targeting drugs

Research at the Institute

Stereoselective Entry into α,α’-C-Oxepane Scaffolds through a Chalcogen Bonding Catalyzed Strain-Release C-Septanosylation Strategy
Orpinolide disrupts a leukemic dependency on cholesterol transport by inhibiting OSBP
Tissue-intrinsic beta-catenin signals antagonize Nodal-driven anterior visceral endoderm differentiation
Transient Structural Properties of the Rho GDP-Dissociation Inhibitor
Tafbromin selectively targets the TAF1 bromodomain
A validation strategy to assess the role of phase separation as a determinant of macromolecular localization
Asymmetric Pd/Organoboron-Catalyzed Site-Selective Carbohydrate Functionalization with Alkoxyallenes Involving Noncovalent Stereocontrol
Molecular mechanism of actin filament elongation by formins
Harnessing Multistep Chalcogen Bonding Activation in the α-Stereoselective Synthesis of Iminoglycosides
Structure of the human KMN complex and implications for regulation of its assembly
A divergent intermediate strategy yields biologically diverse pseudo-natural products
N-Cyanopiperazines as Specific Covalent Inhibitors of the Deubiquitinating Enzyme UCHL1
Yersinia entomophaga Tc toxin is released by T10SS-dependent lysis of specialized cell subpopulations
Selected Publications 2023
Exploiting π and Chalcogen Interactions for the β-Selective Glycosylation of Indoles through Glycal Conformational Distortion
Structure and activation mechanism of the Makes caterpillars floppy 1 toxin
Cooperative Bifurcated Chalcogen Bonding and Hydrogen Bonding as Stereocontrolling Elements for Selective Strain-Release Septanosylation
Discovery of a Drug-like, Natural Product-Inspired DCAF11 Ligand Chemotype
RZZ-Spindly and CENP-E form an integrated platform to recruit dynein to the kinetochore corona
Structure of the native myosin filament in the relaxed cardiac sarcomere
The modes of action of ion-channel-targeting neurotoxic insecticides: lessons from structural biology. 
Synthetic Matching of Complex Monoterpene Indole Alkaloid Chemical Space
Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments
Native Semisynthesis of Isopeptide-Linked Substrates for Specificity Analysis of Deubiquitinases and Ubl Proteases
Structural basis of mRNA binding by the human FERRY Rab5 effector complex
Programming inactive RNA-binding small molecules into bioactive degraders
Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding
Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding
Structural Biochemistry of Muscle Contraction
The EGFR phosphatase RPTPγ is a redox-regulated suppressor of promigratory signaling.
Targeting oncogenic KRasG13C with nucleotide-based covalent inhibitors
The structural flexibility of MAD1 facilitates the assembly of the Mitotic Checkpoint Complex
Morphological profiling identifies the motor protein Eg5 as cellular target of spirooxindoles
Selected Publications 2022
 A synergistic Rh(I)/organoboron-catalysed site-selective carbohydrate functionalization that involves multiple stereocontrol
A cryogenic, coincident fluorescence, electron and ion beam microscope
Structural basis of actin filament assembly and aging
Structural basis for specific inhibition of the deubiquitinase UCHL1
CRISPR screens in Drosophila cells identify Vsg as a Tc toxin receptor
Conformational transitions of the Spindly adaptor underlie its interaction with Dynein and Dynactin
CDC20 assists its catalytic incorporation in the mitotic checkpoint complex
A self-organized synthetic morphogenic liposome responds with shape changes to local light cues
Overlap of NatA and IAP substrates implicates N-terminal acetylation in protein stabilization
Cryo-EM resolves molecular recognition of an optojasp photoswitch bound to actin filaments in both switch states
Cell-Based Identification of New IDO1 Modulator Chemotypes
The molecular basis for sarcomere organization in vertebrate skeletal muscle
Natural product fragment combination to performance-diverse pseudo-natural products
Growth factor–dependent ErbB vesicular dynamics couple receptor signaling to spatially and functionally distinct Erk pools
Assembly principles and stoichiometry of a complete human kinetochore module
Dynamic Catalytic Highly Enantioselective 1,3-Dipolar Cycloadditions
Combination of pseudo-natural product design and formal natural product ring distortion yields stereochemically and biologically diverse pseudo-sesquiterpenoid alkaloids
A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks
Exploiting non-covalent interactions in selective carbohydrate synthesis
 Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens
High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism.
Molecular architecture of black widow spider neurotoxins
Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM
Targeted substrate loop insertion by VCP/p97 during PP1 complex disassembly
Synthesis of 20-Membered Macrocyclic Pseudo-Natural Products Yields Inducers of LC3 Lipidation
Selected Publications 2021
Synthesis of 20-Membered Macrocyclic Pseudo-Natural Products Yields Inducers of LC3 Lipidation
Structure of the Mon1-Ccz1 complex reveals molecular basis of membrane binding for Rab7 activation
On the role of phase separation in the biogenesis of membraneless compartments
Structures from intact myofibrils reveal mechanism of thin filament regulation through nebulin
Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores
Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization
Mechanism of threonine ADP-ribosylation of F-actin by a Tc toxin
Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector
Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype
Selected Publications 2020
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