Recruiting Faculty
Prof. Dr. Dorothee Dormann
Johannes Gutenberg University Mainz - Institute of Molecular Biology (IMB)Neurodegeneration
Research Mission
Our research focuses on the molecular mechanisms of RNA-binding protein (RBP) dysfunction in neurodegenerative diseases, most notably the currently incurable disorders ALS (amyotrophic lateral sclerosis), FTD (frontotemporal dementia), and Alzheimer's disease. We aim to understand how specific, disease-linked RBPs, such as TDP-43 and FUS, mislocalize and aggregate in these disorders, to provide a mechanistic basis for new therapeutic strategies.
Experimental Techniques
We dissect the complex pathomechanism using a reductionist approach based on in vitro reconstitution and cellular experiments. We use recombinant proteins, protein/RNA biochemistry and biophysics to understand molecular events. As cellular models, we mostly use mammalian cell lines. We use techniques such as confocal microscopy, live cell imaging, protein-RNA interaction and phase separation assays, and employ genomics and proteomics approaches.
Selected Publications
Disease-linked TDP-43 hyperphosphorylation suppresses TDP-43 condensation and aggregation
EMBO Journal 2022
Phase Separation of FUS Is Suppressed by Its Nuclear Import Receptor and Arginine Methylation
Cell 2018
Prof. Dr. Achilleas Frangakis
Goethe University Frankfurt - Institute of BiophysicsBioimaging
Research Mission
Cell adhesion is an essential process that allows for cells to attach and interact with other cells and their environment in order to perform a multitude of tasks. Although adhesion is directly related to infection processes and disease, it is currently only poorly understood. Our mission is to study and decipher the adhesion mechanisms of both eukaryotic and bacterial cells.
Experimental Techniques
We use a large arsenal of different technologies to complement our primary methodologies of cryo-electron tomography, image processing and machine learning. Our main model system to study bacterial adhesion is M. pneumoniae & genitalium. For eukaryotic systems we utilise various endothelial and epithelial cell lines.
Prof. Dr. Ana García Sáez
MPI of BiophysicsBioimaging
Research Mission
Our department aims at understanding the underlying physical principles and molecular mechanisms that govern membrane organization and dynamics. A key open question is how membrane behavior and signaling are coordinated by the interplay between molecular components and the membrane properties. We focus our research on the mitochondrial alterations during apoptosis as well as on membrane permeabilization as a common theme in regulated cell death.
Experimental Techniques
We have established a multi-disciplinary department that develops new microscopy tools and combines biophysics, biochemistry and cell biology in reconstituted minimal systems and in single cells to analyze mitochondrial permeabilization and additional alterations during apoptosis from a quantitative perspective. We also apply these methods to study the molecular mechanisms of membrane permeabilization that execute other forms of cell death.
Selected Publications
The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial DNA-mediated inflammation
Molecular Cell 2022
DRP1 interacts directly with BAX to induce its activation and apoptosis
EMBO Journal 2022
BCL-2-family protein tBID can act as a BAX-like effector of apoptosis
EMBO Journal 2022
Dr. Bernhard Hampölz
MPI of Biophysics - Molecular SociologyCell Biology
Research Mission
Our aim is to better understand how macromolecular complexes and in particular the Nuclear Pore Complex (NPC) assemble in the context of animal development. To that end we use embryos and the female germline of the fruitfly Drosophila melanogaster to delineate principles of how NPCs form in a multicellular organism and how their assembly relies on the major regulatory inputs of early development.
Experimental Techniques
Our methodological repertoire is broad and spans techniques as diverse as cultivating and crossing fruitfly lines (aka “Fly pushing”) and in vitro biochemistry. This spectrum contains Drosophila genetics, general cell biological techniques, organ dissection, plastic and Cryo-EM (including CLEM). Our core technology is imaging of living Drosophila embryos, ovaries and larval brains.
Selected Publications
Nuclear Pores Assemble from Nucloporin Condensates During Oogenesis
Cell 2019
Pre-assembled Nuclear Pores Insert Into the Nuclear Envelope During Early Development
Cell 2016
Prof. Dr. Inga Hänelt
Goethe University Frankfurt - Institute of BiochemistryBiochemistry
Research Mission
Proteins involved in substrate translocation across biological membranes are diverse and the variety that nature has evolved to control substrate flux absolutely fascinates us. A major focus of my group is on bacterial membrane transport systems and, in particular, potassium transport systems that are essential for the survival of a single cell and a bacterial community, namely biofilms.
Experimental Techniques
Our lab applies a variety of methods, including biochemistry, structural biology, EPR spectroscopy, microbiology and electrophysiology for understanding the molecular principles of membrane transport proteins.
Prof. Dr. Gerhard Hummer
MPI of Biophysics - Theoretical BiophysicsBiophysics
Research Mission
We use molecular dynamics simulations and integrative modeling to study biological systems from molecular to organellar scales. Focus areas include the dynamics of the nuclear pore complex; membrane remodeling in cell homeostasis, autophagy and viral infection; and membrane channel and transporter function. To tackle issues of size and complexity in molecular dynamics simulations at organellar scales, we develop novel simulation and AI methods.
Experimental Techniques
We use a wide range of computational and theoretical techniques including molecular dynamics simulations; integrative modeling; artificial intelligence / machine learning; statistical physics; computational physics; theoretical chemistry; quantum chemistry; computational chemistry; bioinformatics; high-performance computation; kinetic modeling; stochastic processes; and Bayesian statistics.
Selected Publications
Artificial intelligence reveals nuclear pore complexity
bioRxiv 2022
Global structure of the intrinsically disordered protein tau emerges from its local structure
JACS Au 2022
Membrane fusion and drug delivery with carbon nanotube porins
Proc. Natl. Acad. Sci. U.S.A. 2021
FAM134B-RHD protein clustering drives spontaneous budding of asymmetric membranes
J. Phys. Chem. Lett. 2022
In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
Science 2021
Prof. Dr. Edward A Lemke
Johannes Gutenberg University Mainz - Institute of Molecular Biology (IMB)Biophysics
Research Mission
We focus on studying intrinsically disordered proteins (IDPs), which constitute up to 50% of the eukaryotic proteome. IDPs are found in many vital biological processes, such as nucleocytoplasmic transport, transcription and gene regulation. The ability of IDPs to exist in multiple conformations is considered a major driving force behind their enrichment during evolution in eukaryotes.
Experimental Techniques
Using a question-driven, multidisciplinary approach paired with novel tool development in miroscope engeenering, chemical biology, synthetic biology and microfludics, we have made major strides in understanding the biological dynamics of such systems from the single molecule to the super resolved whole cell level.
Selected Publications
Visualizing the disordered nuclear transport machinery in situ
Nature 2023
Dr. Melanie McDowell
MPI of BiophysicsStructural Biology
Research Mission
Almost all eukaryotic membrane proteins start their life in the cytosol and must journey to the cellular membrane where they function. Multiple pathways are employed to recognise different classes of membrane proteins, deliver them to the correct membrane and insert them into the lipid bilayer. We strive to understand the protein factors involved in these pathways at the endoplasmic reticulum, the primary destination for most membrane proteins.
Experimental Techniques
We use an integrative approach to study protein structure, interactions and function. Techniques include cryo-EM, x-ray crystallography, biophysical methods, in vitro biochemical reconstitution and pull-outs of native protein complexes from model organisms such as yeast and Chaetomium thermophilum.
Selected Publications
Structural and molecular mechanisms for membrane protein biogenesis by the Oxa1 superfamily
Nature Structural and Molecular Biology 2021
Structural basis of tail-anchored membrane protein biogenesis by the GET insertase complex
Molecular Cell 2020
Prof. Dr. Nina Morgner
Goethe University Frankfurt - Institute of Physical and Theoretical ChemistryPhysical Chemistry
Research Mission
Cellular function is generally controlled by non-covalent interactions between proteins and other biomolecules. We investigate such interactions, molecular machines and their assembly by means of native mass spectrometry (MS). Where current technology is not sufficient to answer we further develop mass spectrometric instrumentation.
Experimental Techniques
Our research makes use of two different non-covalent MS methods. One is the commercially available nESI-MS method, the other LILBID MS, which we develop in house.
Selected Publications
Bacterial F-type ATP synthases follow a well-choreographed assembly pathway.
Nature communications 2022
LILBID laser dissociation curves: a mass spectrometry-based method for the quantitative assessment of dsDNA binding affinities.
Scientific reports 2020
Structural rearrangement of amyloid-β upon inhibitor binding suppresses formation of Alzheimer’s disease related oligomers
eLife 2020
Prof. Dr. Michaela Müller-McNicoll
Goethe University Frankfurt - Institute for Molecular Bio ScienceGene Regulation
Research Mission
RNA binding proteins with low complexity domains (LCDs) often assemble nuclear compartments or large RNA-protein particles under stress. We study how RNA-protein interactions organize subcellular architecture and coordinate the regulation of gene expression during cellular stress and differentiation. Our goal is to understand how different steps in gene expression are interconnected in time and separated in space.
Experimental Techniques
Using pluripotent cells as a model system, we combine various methods including smRNA FISH, imaging, protein/RNA Biochemistry, iCLIP, Ribo-seq, metabolic labelling, reporter gene studies, mass spectrometry, CRISPR mutagenesis and RNA bioinformatics to obtain mechanistic insights. We also develop new methods and assays to get a quantitative and high-resolution picture of gene expression in the context of a compartmentalized cell.
Selected Publications
Poison exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia.
Nucleic Acids Research 2023
SRSF3 and SRSF7 affect 3’UTR length in opposite directions through suppression or activation of proximal poly(A)-sites and regulation of CFIm levels.
Genome Biology 2021
SRSF7 maintains its homeostasis through the expression of Split-ORFs and nuclear body assembly
Nature Structural Molecular Biology 2020
Cellular differentiation state modulates the export activity of SR proteins.
Journal of Cell Biology 2017
hGRAD: A versatile "one-fits-all" system to acutely deplete RNA binding proteins from condensates
Journal of Cell Biology 2024
Prof. Dr. Christian Münch
Goethe University Frankfurt - Institute of Biochemistry II (IBC2)Cell Biology
Research Mission
Cells respond to stress with highly coordinated and dynamic responses. Their full complexity and spatio-temporal control remains poorly understood. We focus on a range of stresses - (mitochondrial) protein misfolding, infection, cancer - to study their effects on a systems biology/medicine level. We aim to define the molecular details of stress responses, their roles in diseases, and potential avenues for therapeutic intervention.
Experimental Techniques
We employ biochemical, cell biological, genetic, and proteomics approaches to comprehensively monitor the multiple facets of stress responses. To grasp dynamic, cell-wide changes, we develop proteomics methods, such as for translation & degradation. We then apply computational approaches on our multi-level data to gain integrated systems information. Our work largely focuses on mammalian cell culture systems and clinical models.
Selected Publications
A cytosolic surveillance mechanism activates the mitochondrial UPR
Nature 2023
Global mitochondrial protein import proteomics reveal distinct regulation by translation and translocation machinery
Molecular Cell 2022
Protein import motor complex reacts to mitochondrial misfolding by reducing protein import and activating mitophagy
Nature Commun 2022
Proteomics of SARS-CoV-2-infected host cells reveals therapy targets
Nature 2020
Functional Translatome Proteomics Reveal Converging and Dose-Dependent Regulation by mTORC1 and eIF2α
Molecular Cell 2020
Prof. Dr. Klaas Martinus Pos
Goethe University Frankfurt - Institute of BiochemistryBiochemistry
Research Mission
We look into the molecular detail of antibiotic efflux pump and lipid transport machineries and how these pumps can provide resistance against many antibiotics. We also research on efflux pump inhibitors, which can be used in combination with existing antibiotics to recover their effectiveness.
Experimental Techniques
We use X-ray crystallography and single-particle Cryo-EM to obtain molecular insight into the mechanisms of antibiotic binding and transport. With biophysical and biochemical methods, we quantify the effectiveness of the efflux pump inhibitors and gain insight into antibiotic interaction with the efflux pump
Selected Publications
Pyridylpiperazine efflux pump inhibitor boosts in vivo antibiotic efficacy against K. pneumoniae.
EMBO Mol Med 2024
Pyridylpiperazine-based allosteric inhibitors of RND-type multidrug efflux pumps
Nat Commun 2022
Allosteric drug transport mechanism of multidrug transporter AcrB
Nat Commun 2021
Dr. Beata Turoňová
MPI of Biophysics - Molecular SociologyStructural Biology
Research Mission
We aim to facilitate in situ structural analysis by developing novel algorithms for cryo electron tomography and subtomogram averaging. Our method development focuses on improving tomogram quality and integrating contextual information into subtomogram averaging routines. The goal is to allow for reliable and objective analysis of tomograms as well as macromolecular complexes.
Experimental Techniques
The main focus is software method development. We use cryo electron tomography, often in combination with focused ion-beam milling, to obtain data for the method development. To ensure their robustness, the methods are tested on a variety of samples from virus-like particles (e.g. HIV, Sars-Cov-2) and real viruses (e.g. Sars-Cov-2, vaccinia) to very large macromolecular complexes (e.g. nuclear pore complexes).
Selected Publications
In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
Science 2020
Benchmarking tomographic acquisition schemes for high-resolution structural biology
Nature Communications 2020
Cone-shaped HIV-1 capsids are transported through intact nuclear pores
Cell 2021
Dr. Janet Vonck
MPI of Biophysics - Structural BiologyStructural Biology
Research Mission
Membrane proteins play essential roles in many cellular processes including transport, creating and maintaining ion gradients, and signaling, between cellular compartments and the cell and its environment. But our knowledge of their structure is still far behind that of soluble proteins. We study the structure and dynamics of membrane proteins and membrane protein complexes by cryo-EM.
Experimental Techniques
We use the pipeline of single-particle cryo-EM from sample vitrification, microscope data collection, image processing and particle reconstruction to model building.
Selected Publications
High-resolution structure and dynamics of mitochondrial complex I – insights into the proton pumping mechanism
Science Advances 7, eabj3221 2021
Structural basis of proton-coupled potassium transport in the KUP family
Nature Communications 11, 626 2020
Structure, mechanism, and regulation of the chloroplast ATP synthase
Science 360, eaat4318 2018
Dr. Florian Wilfling
MPI of BiophysicsCell Biology
Research Mission
Proteins are workhorses of cells and perform a vast array of functions. Often this requires the formation of large multi-protein complexes which act as a macromolecular machine for individual tasks. How disused, damaged or misassembled macromolecular machines are disposed is largely unknown. Our main goal is to systematically identify signals and factors important for surveillance of the assembly and functional state of macromolecular machines.
Experimental Techniques
We integrate a diverse set of techniques including biochemistry, advanced live-cell microscopy, correlative cryo-electron tomography, state-of-the-art quantitative mass spectrometry and unbiased system-wide approaches.
Selected Publications
Selective autophagy degrades nuclear pore complexes
Nature Cell Biology 2020
A selective autophagy pathway for phase separated endocytic protein deposits
Molecular Cell 2020