antonchick andrey-web REACTION METHODOLOGY

Dr. Andrey P. Antonchick


since 2010: Group leader at the Department of Chemical Biology, Max Planck Institute of Molecular Physiology
2008-2010: (PostDoc) Max Planck Institute of Molecular Physiology, Dortmund
2005-2008: (PostDoc) University of Frankfurt
2000-2005: (PhD) Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Research Interest
Organic synthesis; Catalysis; Natural products; Chemical biology

Techniques
Various techniques of organic synthesis, isolation and identification of compounds using physicochemical methods of analysis

Selected Reading
Antonchick A.P., Burgmann L. Direct Selective Oxidative Cross-Coupling of Simple Alkanes with Heteroarenes. Angew Chem Int Ed 2013, 52, 3267-3271.

Matcha K., Antonchick A.P. Metal-Free Cross-Dehydrogenative Coupling of Heterocycles with Aldehydes. Angew Chem Int Ed 2013, 52, 2082-2086.


Antonchick A.P., Samanta R., Kulikov K., Lategahn J. Organocatalytic, Oxidative, Intramolecular C–H Bond Amination and Metal-free Cross-Amination of Unactivated Arenes at Ambient Temperature. Angew Chem Int Ed 2011, 50, 8605-8608.

Samanta R., Antonchick A.P. Palladium-Catalyzed Double C–H Activation Directed by Sulfoxides in the Synthesis of Dibenzothiophenes. Angew Chem Int Ed 2011, 50, 5217-5220.

Samanta R., Matcha K., Antonchick A.P. Metal-Free Oxidative Carbon-Heteroatom Bond Formation Through C–H Bond Functionalization. Eur J Org Chem 2013, 5769-5804.

Read more ...


 

bastiaens philippe-web IMPACT OF DYNAMICS AND SPATIAL ORGANIZATION OF SIGNALLING MOLECULES/ACTIVITIES ON CELL PHENOTYPE

Prof. Dr. Philippe I.H. Bastiaens

Current Position: 
Director of the Department of Systemic Cell Biology at the Max Planck Institute of Molecular Physiology in Dortmund and Professor of Cell Biology and Biochemistry in the Department of Chemistry and Chemical Biology at the University of Dortmund
Group Leader: 
Cell Biophysics Laboratory at the Imperial Cancer Research Fund, London, UK 
Cell Biology and Biophysics program at the European Molecular Biology Laboratory and Professor at the University in Amsterdam
Postdoc:
Department of Biochemistry at the University of Wageningen
Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
PhD:
Department of Biochemistry, University of Wageningen, The Netherlands

Research Interest
Cellular information processing is traditionally explained by unidirectional causalities between activities of gene products; the so-called signal transduction pathways. Since the inception of the department in 2007 we have taken a different road to investigate how cells process extracellular information by studying how the spatial organization of signaling molecules emerges from their collective dynamics and how this in turn affects cellular response. From this endeavor we came to the conclusion that signal transduction cannot be perceived as originating from a hardwired circuitry, but more as a highly adaptive network that obtains its properties by recursive interactions between biochemical activities of the network itself as well as with the networks of other cells by extracellular communicating factors. In this way the processing of information of the network becomes dependent on historical and extracellular context. We therefore like to think about signaling as a process more reminiscent to cognition. We experimentally and theoretically study properties of biochemical cognitive networks embedded in systems of different scales and context, from reconstituted artificial cells, to tissue culture cells, to cellular assemblies such as organoids.

The approaches in the Department of Systemic Cell Biology are necessarily highly multidisciplinary and range from 1) the development of new single mol­e­cule and functional microspectroscopic tech­niques to image dynamics and spatial patterns of molecu­lar processes, 2) over chemical-biological and ge­netic tools to observe and perturb intracel­lular net­works, 3) to bottom-up biochemical recon­stitution approaches, and 4) computational mod­eling and non-linear dynamics to derive and conceptualize physical principles that underlie the dynamics of signaling and self-organization of living matter.

Techniques
• Functional microscopic imaging approaches (e.g. Fluorescence Lifetime Imaging to measure FRET, 

  Fluorescence Correlation Spectroscopy, Selective Plane Illumination Microscopy, Single Molecule Imaging, 
  Total Internal Reflection Microscopy, Cryo-microscopy…)
• Electron microscopy
• Generation of biosensors for measuring protein activities in living cells
• Development of advanced microscopy techniques and data analysis approaches 
• Simulation approaches for understanding reaction networks in living cells

Selected Reading
Masip ME, Huebinger J, Christmann J, Sabet O, Wehner F, Konitsiotis A, Fuhr GR, Bastiaens PI. Reversible cryo-arrest for imaging molecules in living cells at high spatial resolution. Nat Methods 2016, Jul 11. doi: 10.1038/nmeth.3921.

Schmick, M., Bastiaens, P.I.H. The interdependence of membrane-shape and signal processing in cells. Cell 2014, 156(6):1132-1138. Review.

Schmick M, Vartak N, Papke B, Kovacevic M, Truxius DC, Rossmannek L, Bastiaens, P.I.H. KRas Localizes to the Plasma Membrane by Spatial Cycles of Solubilization, Trapping and Vesicular Transport. Cell 2014, 157(2):459-471.


Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI, Waldmann H. Small molecule inhibition of the KRAS-PDEd interaction impairs oncogenic KRAS signalling. Nature 2013, 497(7451), 638-42.

Chandra A, Grecco HE, Pisupati V, Perera D, Cassidy L, Skoulidis F, Ismail SA, Hedberg C, Hanzal-Bayer M, Venkitaraman AR, Wittinghofer A, Bastiaens PI. The GDI-like solubilizing factor PDEd sustains the spatial organization and signalling of Ras family proteins. Nat Cell Biol 2012, 14(2), 148-58.

Grecco HE, Roda-Navarro P, Girod A, Hou J, Frahm T, Truxius DC, Pepperkok R, Squire A, Bastiaens PI. In situ analysis of tyrosine phosphorylation networks by FLIM on cell arrays. Nat Methods 2010, 7(6), 467-72.

Read more ... 


 

Photo BielingCELL POLARITY AND MORPHOGENESIS

Dr. Peter Bieling

Since 2016: Group Leader at the MPI of Molecular Physiology, Dortmund
2010–2015: Postdoc with Dyche Mullins (UCSF) and Dan Fletcher (UC Berkeley)
2008–2009: Bridging Postdoc with Thomas Surrey (EMBL Heidelberg)
2004–2008: PhD Student with Thomas Surrey (EMBL Heidelberg)
2003–2004: Master thesis with Marina Rodnina (Witten/Herdecke University, now MPI Göttingen)

Research Interest
My lab is interested in the molecular mechanisms that regulate changes in cellular morphology and the underlying polarization of the signaling molecules that control these processes. Nearly all cells display some form of polarity, which allows them to perform spatially complex functions such as movement or the formation of tissues and organs. Polarization requires a complex interplay between biochemical signals that are generated at the plasma membrane and cytoplasmic molecules, most importantly the actin cytoskeleton.

While many key players of cell polarity and morphogenesis are now known, we currently do not understand how spatial signaling systems can break symmetry and how the size and shape of their emerging domains is determined. Importantly, we have not yet managed to re-built systems from defined components that recapitulate membrane polarization in vitro.

Instead of studying membrane polarity and actin assembly in their complex cellular environment, we reconstitute these processes from purified proteins using a bottom-up approach. Using cell motility as a testbed, we test our understanding of these systems by employing synthetic biology techniques to rationally engineer biomimetic networks capable of autonomously breaking membrane symmetry. Combining multi-protein reconstitution with advanced fluorescence imaging (TIRFM, FLIM) down to the level of single molecules allows us to study and manipulate all biochemical activities in great detail to reveal the design principles underlying protein self-organization.

Techniques
in vitro reconstitution, bio-mimetic membrane systems, advanced fluorescence techniques (TIRF, FLIM, single molecule imaging), synthetic biology

Selected Reading
Bieling P, Li T-D, Weichsel J, McGorty R, Jreij P, Huang B, Fletcher DA, Mullins RD. Force Feedback Controls Motor Activity and Mechanical Properties of Self-Assembling Branched Actin Networks. Cell 2016, 164, 115-27.

Bieling P, Telley IA, Surrey T. A minimal midzone protein module controls formation and length of antiparallel microtubule overlaps. Cell 2010, 142, 420-32.

Bieling P, Laan L, Schek H, Munteanu EL, Sandblad L, Dogterom M, Brunner D, Surrey T. Reconstitution of a microtubule plus-end tracking system in vitro. Nature 2007, 450, 1100-5.

Read more....


DSC 7226 C-alex-birdCELLULAR REGULATION OF MICROTUBULE NETWORKS

Dr. Alex Bird

Research Interest
Microtubules play important roles in a variety of cellular processes, including cell division, cell migration, and neuronal morphogenesis. The microtubule polymer is highly dynamic within cells, and a large number of microtubule-associated proteins (MAPs) interact with microtubules and modulate their dynamics, nucleation, and stability, as well as their interactions with other proteins and organelles. The precise regulation of microtubule dynamics and interactions differs over cell development, the cell cycle, and intracellular space, and is essential to the cellular processes in which microtubules function. Misregulation of these properties can lead to disease progression, and it is thus important to understand how changes in microtubule dynamics facilitate function, and how these changes are regulated. We study how MAPs regulate microtubule functions to facilitate cell division, cell migration, and neuronal morphogenesis.

Techniques
Genome Engineering (CRISPR/Cas9 and BAC (Bacterial Artificial Chromosome) recombineering/transgenesis
• Advanced fixed and live-cell fluorescence microscopy
Mammalian cell culture (cancer cell, embryonic stem cells)
Protein Biochemistry

Selected Reading
Bendre S, Rondelet A, Hall C, Woestehoff N, Lin YC, Brouhard GJ, Bird AW. GTSE1 tunes microtubule dynamics for chromosome alignment and segregation through MCAK inhibition. (preprint) bioRxiv 2016, doi: 10.1101/067827.

Scolz M, Widlund PO, Piazza S, Bublik DR, Reber S, Peche LY, Ciani Y, Hubner N, Isokane M, Monte M, Ellenberg J, Hyman AA, Schneider C, and Bird AW. GTSE1 is a Microtubule Plus-end Tracking Protein that Regulates EB1-dependent Cell Migration. PloS One 2012, 7(12)e51259.

Bird AW, Erler A, Fu J Hériché J-K, Maresca M, Zhang Y, Hyman AA and Stewart AF. High efficiency counterselection recombineering for site-directed mutagenesis in bacterial artificial chromosomes. Nat Methods 2012, 9(1), 103-9.

Hubner NC*, Bird AW*, Cox J, Splettstoesser B, Bandilla P, Poser I, Hyman A, Mann M. Quantitative proteomics combined with BAC TransgeneOmics reveals in vivo protein interactions. J Cell Biol 2010, 189(4), 739-54. (*equal contribuiton)

Bird AW, Hyman AA. Building a spindle of the correct length in human cells requires the interaction between TPX2 and Aurora A. J Cell Biol 2008, 182(2), 289-300.

Read more ...

 


 

Foto BoosVERTEBRATE DNA REPLICATION

Dr. Dominik Boos

Since 2014: Independent group leader ZMB, Essen
2007-2014: Postdoc in the lab of John Diffley, LRI Clare Hall Laboratories, UK
2002-2007: PhD thesis in the lab of Olaf Stemmann, MPI for Biochemistry, Martinsried, Germany

Research Interest
We investigate fundamental molecular mechanisms and regulations of DNA replication. The focus is on vertebrate tissue culture cells because little is known in higher eukaryotes about this. The lab is particularly interested in the initiation step of replication, as this is a pivotal step of regulation of replication in a variety of cellular contexts. Appropriately controlled initiation: 1) couples replication to the S phase of the cell cycle, 2) regulates replication upon DNA damage, and 3) mediates the right temporal control of cellular replication. Thus, the proper regulation of initiation critically determines efficiency and accuracy of genome duplication.

In the next years the lab will concentrate on a major regulation hub of replication initiation, the Treslin-MTBP-TopBP1 protein complex. We investigate aspects of its molecular and cellular functions, regulations in unperturbed cell cycles and upon DNA damage, as well as its impact on cancer formation.

Techniques

We mainly use human tissue culture, RNAi and various cell biological and biochemical techniques to analyse protein functions. We complement this by in vitro biochemistry for insight into molecular details. In the future we may also use Xenopus egg extracts as a biochemically tractable model system.

Selected Reading

Boos D, Yekezare M and Diffley JFX. Identification of a heteromeric complex that promotes DNA replication origin firing in human cells. Science 2013, 340, 981-983.

Boos D, Sanchez-Pulido L, Rappas M, Pearl LH, Oliver AW, Ponting CP and Diffley JFX. Regulation of DNA Replication through Sld3-Dpb11 Interaction Is Conserved from Yeast to Humans. Curr Biol 2011, 21, 1152-1157.

Boos D*, Frigola J* and Diffley JFX. Activation of the replicative DNA helicase:breaking up is hard to do. Review; Curr Op Cell Biol 2012, 24, 1–8. (*equal contribution)

Read more ...

 


 

BraunschweigerSYNTHESIS AND SCREENING OF DNA-ENCODED LIBRARIES

Dr. Andreas Brunschweiger

Current Position: Group Leader Medicinal Chemistry, Faculty for Chemistry and Chemical Biology, TU Dortmund
Postdoc: ETH Zürich, Institute for Pharmaceutical Sciences
Ph D: University of Bonn, Institute for Pharmaceutical Chemistry

Research Interest
Synthesis of functionalized small molecule scaffolds, development of DNA-compatible catalytic methods for small molecule synthesis, development and application of selection-based screening assays


Techniques
Organic preparative synthesis, synthesis of oligonucleotide-small molecule conjugates, combinatorial synthesis on the nanomolar scale, HPLC, LC-MS, Maldi-TOF, Q-PCR, selection-based screening.


Read more ...


 

dehmelt leif-webSPATIO-TEMPORAL REGULATION OF THE NEURONAL CYTOSKELETON

Dr. Leif Dehmelt

since 2011: Group leader at the MPI Dortmund, Dept. of Systemic Cell Biology
since 2007: Group leader at the TU Dortmund, Faculty of Chemistry and Chemical Biology
2000–2007: Postdoc at The Scripps Research Institute, La Jolla, USA, Dept. of Cell Biology
1997-2000: PhD thesis at the MPI Dortmund, Dept. of Epithelial Physiology

Research Interest
Cellular and molecular processes in the functional and morphological differentiation of neurons play a key role in the development of the brain. Misregulation of those processes, for example due to aging, mutations or intake of toxic compounds, can lead to serious brain lesions. Thus, a better understanding of the underlying cellular and molecular mechanisms is central to a fundamental and holistic understanding of normal and perturbed brain development and function.
In our lab, we study fundamental molecular and cellular processes in neuronal development and how those are affected by modulation of key cellular components. Our focus is on the cytoskeleton, as this cellular component plays a key role in defining the morphology and thereby the correct function of developing neurons. In earlier studies, we found that the main cyotoskeleton components, actin and microtubules, are coordinated with each other during the first formation of a neuronal protrusion. To understand this complex coordination of dynamic cellular components, we implement a systems biology approach that combines acute experimental perturbations, development of novel analysis technologies and mathematical modeling.

Techniques
- live cell microscopy (total internal reflection fluorescence, single molecule analysis)
- development of novel protein interaction analysis methods (intracellular protein interaction arrays)

- signal network analysis and perturbation in living cells
- stem cell technologies
- morphometric high-content screening
- computational modeling

Selected Reading
Mazel T, Biesemann A, Krejczy M, Nowald J, Müller O and Dehmelt L. Direct observation of microtubule pushing by cortical dynein in living cells. Mol Biol Cell 2014, 25, 95.

Arens J, Duong T-T and Dehmelt L. A Morphometric Screen Identifies Specific Roles for Microtubule-Regulating Genes in Neuronal Development of P19 Stem Cells. PLoS One 2013, 8, e79796.

Gandor S, Reisewitz S, Venkatachalapathy M, Arrabito G, Reibner M, Schröder H, Ruf K, Niemeyer CM, Bastiaens PIH, Dehmelt L. A Protein Interaction Array Inside a Living Cell. Angew Chem Int Ed 2013, 52, 4790.

Dehmelt L and Bastiaens PI. Spatial organization of intracellular communication: insights from imaging. Nat Rev Mol Cell Biol 2010, 11(6), 440-52. 

Read more ...


 

ehrmann michael-webPROTEIN QUALITY CONTROL

Prof. Dr. Michael Ehrmann

Current Positions: W3 Prof. of Microbiology, University of Duisburg-Essen;
Professorial Research Fellow, School of Biosciences, Cardiff University, UK
Group Leader: University of Konstanz, Germany
Postdoc: Harvard Medical School, Boston, MA, USA (Jon Beckwith)
PhD: University of Konstanz, Germany (Winfried Boos)

Research Interest
Mechanism and Translational Aspects of Protein Quality Control
Using the widely conserved HtrA family of serine proteases as a model, we are studying evolutionarily conserved cellular factors that are involved in key
aspects of quality control, such as detection of misfolded proteins, signal recognition and integration into the unfolded protein response pathways and regeneration of the functional state. These studies aim at revealing the general concepts governing the underlying molecular mechanisms of protein diagnosis, repair and degradation. Work on human HTRA1 showed involvements in cancer, arthritis and Alzheimer's disease.


Techniques
Biochemistry, Bacterial and Mammalian Cell Biology, Molecular Genetics, Structural Biology, Chemical Biology, Analyses of patient samples

Selected Reading
Poepsel S, Sprengel A, Sacca B, Kaschani F, Kaiser M, Gatsogiannis C, Raunser S, Clausen T, Ehrmann M. Determinant of amyloid fibril degradation by the PDZ protease HTRA1. Nat Chem Biol 2015, 11, 862-9.

Mastny M, Heuck A, Kurzbauer R, Heiduk A, Boisguerin P, Volkmer R, Ehrmann M, Rodrigues CD, Rudner DZ, Clausen T. CtpB assembles a gated protease tunnel regulating cell-cell signaling during spore formation in Bacillus subtilis. Cell 2013, 155, 647–58.

Malet H, Canellas F, Sawa J, Yan J, Thalassinos K, Ehrmann M, Clausen T, Saibil HR. Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ. Nat Struct Mol Biol 2012, 19, 152-7.

Merdanovic M, Clausen T, Kaiser M, Huber R, Ehrmann M. Protein quality control in the bacterial periplasm. Annu Rev Microbiol 2011, 65, 149-68.

Clausen T, Kaiser M, Huber R, Ehrmann M. HTRA proteases: regulated proteolysis in protein quality control. Nat Rev Mol Cell Biol 2011, 12, 152-62.

Trübestein L, Tennstaedt A, Mönig T, Krojer T, Canellas F, Kaiser M, Clausen T, Ehrmann M. Substrate-induced remodeling of the active site regulates human HTRA1 activity. Nat Struct Mol Biol 2011, 18, 386-8.

Merdanovic M, Mamant N, Meltzer M, Poepsel S, Auckenthaler A, Melgaard R, Hauske P, Nagel-Steger L, Clarke AR, Kaiser M, Huber R, Ehrmann M. Determinants of structural and functional plasticity of a widely conserved protease chaperone complex. Nat Struct Mol Biol 2010, 17, 837-43.

Krojer T, Pangerl K, Kurt J, Sawa J, Stingl C, Mechtler K, Huber R, Ehrmann M, Clausen T. Interplay of PDZ and protease domain of DegP ensures efficient elimination of misfolded proteins. Nature 2008, 453, 885-90.

Ehrmann M and Clausen T. Proteolysis as a regulatory mechanism. Annu Rev Genet 2004, 38, 709-24.

Wilken C, Kitzing K, Kurzbauer R, Ehrmann M, Clausen T. Crystal structure of the DegS stress sensor: How a PDZ domain recognizes misfolded protein and activates a protease. Cell 2004, 117, 483-94 (Highlighted in 2004 Cell 117:417-9).

Krojer T, Garrido-Franco M, Huber R, Ehrmann M, Clausen T. Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine. Nature 2002, 416, 455-9 (Highlighted in 2002 Nat Rev Mol Cell Biol 3:310).

Spiess C, Beil A, Ehrmann M. A temperature-dependent switch from chaperone to protease in a widely conserved heat shock protein. Cell 1999, 97, 339-47.


Read more ...

 


 

erdmann ralf-webPROTEIN IMPORT INTO PEROXISOMES

Prof. Dr. Ralf Erdmann

since 2009: Chair of System Biochemistry (W3), Faculty of Medicine, RUB
2002-2009: Chair of System Biochemistry (C4), Faculty of Medicine, RUB
1998-2002: Associate Professor (C3) of Biochemistry, Free University Berlin
1995-1998: Assistant Professor (C1), RUB
1994-1995: Research Associate, Howard Hughes Medical Institute, New York
1991-1994: Rockefeller University, Lab of Günter Blobel, New York
1989-1991: Research Associate, RUB
1986-1989: PhD, Ruhr- University Bochum (RUB)

Research Interest
Peroxisomes are ubiquitous cellular organelles that are surrounded by a single membrane, multiply by division and de novo formation from the ER and play essential roles in lipid metabolism. Defects in peroxisome function of biogenesis are responsible for devastating human disorders, the mostly lethal peroxisomal diseases. Peroxisomal matrix proteins contain specific peroxisomal targeting signals (PTS1 or PTS2) that are post-translationally recognized and bound in the cytosol by the peroxisomal import receptors, which direct the receptor-cargo complex to the peroxisomal membrane. The cargo-loaded receptors insert into the peroxisomal membrane and assemble with other membrane proteins to form the translocon, which as a transient pore allows the translocation of the folded proteins across the membrane.

Research Focus
• Biogenesis and function of peroxisomes

• Structure and dynamics of the peroxisomal translocon
• Elucidation of the mechanism of the translocation of folded protein across the peroxisomal membrane
• Regulation of the function of the translocon

Techniques
All common biochemical, cell biological and molecular biological techniques are established in the lab.

Selected Reading
Neuhaus A, Kooshapur H, Wolf J, Meyer NH, Madl T, Saidowsky J, Hambruch E, Lazam A, Jung M, Sattler M, Schliebs W, Erdmann R. A Novel Pex14 Protein-interacting Site of Human Pex5 Is Critical for Matrix Protein Import into Peroxisomes. J Biol Chem 2014, 289, 437-48.

Hasan S, Platta HW, Erdmann R. Import of proteins into the peroxisomal matrix. Front Physiol 2013, 4, 261.


Meinecke M, Cizmowski C, Schliebs W, Krüger V, Beck S, Wagner R, Erdmann R. The peroxisomal importomer constitutes a large and highly dynamic pore. Nat Cell Biol 2010, 12, 273-7.

Schliebs W, Girzalsky W, Erdmann R. Peroxisomal protein import and ERAD: variations on a common theme. Nat Rev Mol Cell Biol 2010, 11, 885-90.


Platta HW, El Magraoui F, Schlee D, Grunau S, Girzalsky W, Erdmann R. Ubiquitination of the peroxisomal import receptor Pex5p is required for its recycling. J Cell Biol 2007, 177, 197-204.

Platta HW, Grunau S, Rosenkranz K, Girzalsky W, Erdmann R. Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol. Nat Cell Biol 2005, 8, 817-822.

Erdmann and Schliebs W. Peroxisomal matrix protein import: the transient pore model. Nat Rev Mol Cell Biol 2005, 6, 738-42.

Read more ...

 


 

gerwert-webCHAIR OF BIOPHYSICS AT RUHR UNIVERSITY BOCHUM

Prof. Dr. Klaus Gerwert

Current Position: since 1993 Chair of Biophysics at the Ruhr-University, Professor (W3), Ruhr University Bochum, Germany
Group Leader:
1990-1993, Heisenberg-fellow, Scripps Research Institute, La Jolla, USA & MPI Dortmund

Postdoc: 1986-1989, Max-Planck-Institute, Dortmund
PhD:
1982-1985, Biophysical Chemistry, University of Freiburg


Research Interest
- Biophotonics

- Molecular Reaction Mechanisms of Proteins
- Role of Protein Bound Water
- Vibrational Imaging of Tissue (FTIR) and Cells (Raman)
- Biomarkers

Techniques
- Protein-Biochemistry

- Time Resolved FTIR & Vibrational Imaging (IR-/Raman-/CARS)
- Biomolecular Simulations (MD & QM/MM)
- X-Ray Crystallography

Selected Reading
Garczarek F, Gerwert K. Functional Waters in Protein Proton Transfer. Nature 2006, 439, 109-112.


Freier E, Wolf S, Gerwert K. Proton transfer via a transient linear water-molecule chain in a membrane protein. Proc Natl Acad Sci USA 2011, 108, 11435-9.

Rudack, T., Fei X., Schlitter, J., Kötting, C. and Gerwert, K. Ras and GTPase-activating protein (GAP) drive GTP into a precatalytic state as revealed by combining FTIR and biomolecular simulations. Proc Natl Acad Sci 2012, 109, 15295-15300.

Kallenbach-Thieltges A, Großerüschkamp F, Mosig A, Diem M, Tannapfel A, Gerwert K. Immunohistochemistry, histopathology and infrared spectral histo-pathology of colon cancer tissue sections. J. Biophotonics 2013, 6 (1), 88-100.

El-Mashtoly SF, Petersen D, Yosef HK, Mosig A, Reinacher-Schick A, Kötting C, Gerwert K. Label-Free Imaging of Molecular Targeted Agent Erlotinib in Colon Cancer Cells by Raman Microscopy. Analyst 2014, 139(5), 1155-61.

Read more ...


 

SH-webTHERAPEUTIC TRANSCRIPTOME MODIFICATIONS

Dr. Sven Hennig

Current Position: Independent group leader at the Chemical Genomics Centre (CGC) of the Max Planck Society
Postdoc:
Chemical Genomics Centre - CGC (Prof. Cr. Christian Ottmann), Western Australian Insitute for Medical Research – WAIMR (Dr. A. H. Fox)

PhD: Max-Planck Insitute Dortmund, Germany (Dep. Prof. Dr. A. Wittinghofer, group: Prof Dr. Eva Wolf)

Research Interest
The 'Transcriptome' is the total sum of all transcriptional products within a cell. As Transcription is a tightly regulated process, misregulation usually causes a broad variety of diseases. Fixing these misregulated states for the good of mankind is what we mean by 'Therapeutic'. This implies that at the end of the day we want to develop drugs. These will be small molecules as therapeutics or at least therapeutical precursors specific for each of those diseases. Finally, their mode of action is the desired 'Modification' specifically needed to fix the misbalance in the cell or - at the very end - the organism. As a common scope we focus on direct bimolecular interactions and their modifications. This can either be an inhibition or a stabilization of the complex and thereby activating or de-activating its function. As examples for protein-protein interaction modifications we choose the SMAD family of adaptor proteins and their transcription modifying target proteins. A second class of interactions we want to target are long non-coding RNAs (lncRNAs) and their target proteins. lncRNAs belong to a novel class of biologically active molecules and differ from other ncRNAs in their size.
Plasmid Cloning, Eucaryotic Tissue Culture, RT/qPCR, RNA Tagging, Protein Purification, in vitro Assay Design, Small Molecule Screening, X-ray Crystallography, Isothermal Titration Calorimetry

Selected Reading
Thiel P, Kaiser M, Ottmann C. Small-molecule stabilization of protein-protein interactions: an underestimated concept in drug discovery? Angew Chem Int Ed 2012, 51(9), 2012-8. doi: 10.1002/anie.201107616. Epub 2012 Feb 3.
http://www.ncbi.nlm.nih.gov/pubmed/22308055

Cheetham SW, Gruhl F, Mattick JS, Dinger ME. Long noncoding RNAs and the genetics of cancer. Br J Cancer 2013, 108(12), 2419-25. doi: 10.1038/bjc.2013.233. Epub 2013 May 9.

http://www.ncbi.nlm.nih.gov/pubmed/23660942


Read more ...


 

Hernandez MatiasCELL-CELL MEMBRANE FUSION

Matías Hernández, PhD

Current Position: Group leader at the Max Planck Institute for Molecular Physiology, Dortmund, since 2016
Postdoc: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry (2011-2013), Department of Cellular and Molecular Biophysics, Max Planck Institute for Biochemistry, Martinsried, Germany (2013-2016)
PhD: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany (2007-2011)
BSc and MSc: Chemistry, University of Sydney, Australia (2001-2006)


Research Interest
We aim to uncover the molecular mechanisms responsible for the membrane fusion between cells.  This fundamental process of eukaryotic cell biology is what allows gametes to merge during sexual reproduction, a key evolutionary event in the emergence of complex life in our planet. In addition, cell-cell fusion is required for the development of syncytial tissues such as muscle and the placenta.

Using budding yeast as our model system, we use a range of biochemical and biophysical approaches to identify the molecular players which drive cell-cell membrane fusion. More specifically, we are primarily concerned with the biochemistry at the level of the plasma membrane in an attempt to identify previously uncharacterized proteins with a putative role in fusion. In one approach, we have been conducting proteomic analysis of purified yeast plasma membrane fractions, and are currently studying putative fusogen candidates. In a different complementary approach, we are also constructing novel fusion assays using yeast spheroplasts i.e. cells which have had their cell walls enzymatically removed, thus exposing the plasma membrane to direct biochemical analysis and manipulation.

Techniques
Top-down biochemical reconstitution, membrane biophysics, yeast biology, sub-proteomics, live cell imaging

Selected Reading
Hernandez JM, Kreutzberger AJ, Kiessling V, Tamm LK, Jahn R. Variable cooperativity in SNARE-mediated membrane fusion. Proc Natl Acad Sci 2014 111, 12037–12042.


Aguilar PS, Baylies MK, Fleissner A, Helming L, Inoue N, Podbilewicz B, Wang H, Wong M. Genetic basis of cell–cell fusion mechanisms. Trends Genet 2013, 29, 427–437.

Hernandez JM, Stein A, Behrmann E, Riedel D, Cypionka A, Farsi Z, Walla PJ, Raunser S, Jahn R. Membrane Fusion Intermediates via Directional and Full Assembly of the SNARE Complex. Science 2012, 336, 1581–1584.

Read more ...


kaiser markus-webELUCIDATION OF THE MODE-OF-ACTION OF NATURAL PRODUCTS

Prof. Dr. Markus Kaiser

Current Position: Full professor at the University of Duisburg-Essen, Essen, Germany.
Group Leader:
Independent Group Leader at the Chemical Genomics Centre of the Max-Planck-Society, Dortmund, Germany.
Postdoc:
with Dr. M.-P. Teulade-Fichou and Prof. Dr. J.-M. Lehn, Collège de France, Paris, France.
PhD:
with Prof. Dr. L. Moroder, Max-Planck-Institute of Biochemistry, Martinsried, Germany.


Research Interest
Our group is interested in elucidating the mode-of-action of bioactive compounds, in particular of natural products. To this end, we use preparative organic chemistry as well as chemical proteomics to synthesize, rationally modify and finally to identify the targets of natural products.


Techniques
Natural product synthesis, (chemical) proteomics, activity-based protein profiling (ABPP), protein expression, enzyme assays


Selected Reading
Groll M, Schellenberg B, Bachmann AS, Archer CR, Huber R, Powell TK, Lindow S, Kaiser M, Dudler R. A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism. Nature 2008, 452, 755-758.


Clerc J, Groll M, Illich DJ, Bachmann AS, Huber R, Schellenberg B, Dudler R, Kaiser M. Synthetic and structural studies on Syringolin A and B reveal critical determinants for selectivity and potency of proteasome inhibition. Proc Natl Acad Sci USA 2009, 106, 6507-6512.

Kaschani F, Clerc J, Krahn D, Bier D, Hong TN, Ottmann C, Niessen S, Colby T, van der Hoorn RA, Kaiser M. Identification of a selective, activity-based probe for GAPDHs. Angew Chem Int Ed 2012, 51, 5230-5233.

Stolze SC, Deu E, Kaschani F, Li N, Florea BI, Richau KH, Colby T, van der Hoorn RA, Overkleeft HS, Bogyo M, Kaiser M. The antimalarial natural product symplostatin 4 is a nanomolar inhibitor of the food vacuole falcipains. Chem Biol 2012, 19, 1546-1555.

Read more ...


 

kast stefanTHEORETICAL PHYSICAL CHEMISTRY

Prof. Dr. Stefan M. Kast

Current position: Professor for Theoretical Physical Chemistry, TU Dortmund, Germany.
Group leader and Heisenberg fellow:
at TU Darmstadt, Germany.
Postdoc:
Dept. of Chemistry, University of Chicago, USA.
PhD: Physical Chemistry, TU Darmstadt, Germany.

Research Interest
• Theoretical and computational chemistry

• Statistical mechanics of liquids and solutions
• Electronic structure in solution
• Membrane proteins and ion channels
• Protein-ligand interactions
• Tautomers and protonation states of small molecules

Techniques
• Integral equation theory

• Molecular dynamics simulations
• Quantum chemistry

Selected reading
Kast SM, Kloss T. Closed-Form Expressions of the Chemical Potential for Integral Equation Closures with Certain Bridge Functions. J Chem Phys 2008, 129, 236101.


Tayefeh S, Kloss T, Kreim M, Gebhardt M, Baumeister D, Hertel B, Richter C, Schwalbe H, Moroni A, Thiel G, Kast SM. Model Development for the Viral Kcv Potassium Channel. Biophys J 2009, 96, 485-498.

Kast SM, Heil J, Güssregen S, Schmidt KF. Prediction of Tautomer Ratios by Embedded Cluster Integral Equation Theory. J Comput Aided Mol Des 2010, 24, 343-353.

Kast SM, Kloss T, Tayefeh S, Thiel G. A Minimalist Model for Ion Partitioning and Competition in a K+ Channel Selectivity Filter. J Gen Physiol 2011, 138, 371–373.

Hoffgaard F, Heil J, Kast SM. Three-Dimensional RISM Integral Equation Theory for Polarizable Solute Models. J Chem Theory Comput 2013, 9, 4718–4726.

Read more ...


 

Koseska AnetaCELLULAR COGNITION/DYNAMIC ORGANIZATION PRINCIPLES OF LIVING SYSTEMS

Dr. habil. Aneta Koseska

Since 2016: Group leader, Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund
2013-2015: Project leader, Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund
2012: Guest Professor, Institute of Physics, Humboldt University, Berlin
2007-2011: Researcher, Center for Dynamics of Complex Systems, Potsdam
2004-2007: PhD, Institute of Nonlinear Dynamics, University of Potsdam, Potsdam

Research Interest
We are interested how intercellular communication establishes information processing in cells to dynamically maintain their identity in multicellular context. Studying the relation between topology of signaling networks and their dynamics, both theoretically and experimentally, we investigate how cells in ensembles can generate novel dynamical solutions in terms of biochemical behavior, different than that of isolated cells. We also develop theories and mathematical tools to investigate whether signaling networks are inherently regulated to display rich dynamical behavior at a critical point in a parameter space, thereby determining the right balance between exploration and stability.

Techniques
Mathematical modeling, bifurcation analysis, nonlinear time series analysis, microscopy techniques

Selected Reading
Zou W, Senthilkumar DV, Nagao R, Kiss IZ, Tang Y, Koseska A, Duan J, Kurths J. Restoration of rhythmicity in diffusively coupled dynamical networks. Nat Commun 2015, 7709.

Koseska A, Volkov E, Kurths J. Transition from amplitude to oscillation death via Turing bifurcation. Phys Rev Lett 2013, 111(2):024103.

Koseska A, Volkov E, Kurths J. Oscillation quenching mechanisms: amplitude vs. oscillation death. Physics Reports 2013, 531(4), 173.

Koseska A, Ullner E, Volkov E, Kurths J, García-Ojalvo J. Cooperative differentiation through clustering in multicellular populations. J Theor Biol 2010, 263(2):189-202.


Read more...


 

Metzler-Nolte Niels webMEDICINAL INORGANIC CHEMISTRY

Prof. Dr. Nils Metzler-Nolte

Current Position since 2006: Full Professor, Chair of Inorganic Chemistry I – Bioinorganic Chemistry at Ruhr University Bochum.
2000-2006: Associate Professor (C3) for Medicinal Chemistry, Institute for Pharmacy and Molecular Biotechnology, University of Heidelberg
1996-2000: Group Leader at the MPI für Strahlenchemie, Mülheim
1994-1995: Postdoc with M. L. H. Green, FRS, University of Oxford
1992-1994: PhD on organoboron chemistry, with H. Nöth at LMU, Munich

Research Interest
Our group has research interests in medicinal organometallic chemistry, functional metal bioconjugates, and most recently biocompatible nanoparticles. We aim to exploit the special properties of metal ocmplexes for the detection and modification of biomolecules. Applications of our research include the development of metal-based drugs, e.g. as anti-cancer and anti-microbial agents. We also study the molecular and cell biology of such metal-based drug candidates. Our group has particular expertise in the synthesis and application of metal-conjugates with bioactive peptides and DNA analogues (e.g. peptide nucleic acids). Such conjugates find applications in targeted drugs as well as in biosensors. The group is running the full program of inorganic chemical synthesis and characterization through to cell culture and biochemical investigations.

Techniques
Our group is well equipped for all kinds of chemical synthesis, including Schlenck lines and glove boxes for air-sensitive compounds. We have particular expertise in manual peptide synthesis, but we also use an automated peptide synthesizer. Characterization methods include, but are not limited to NMR, mass spectrometry, optical, IR, and fluorescence spectroscopy, and electrochemical methods. The group runs our own cell culture lab, where we perform functional assays and determine the cytotoxicity of our compounds, as well as compounds from other groups that we study in collaborations. We also use fluroescence microscopy and flow cytometry to study the uptake and intra-cellular localization of metals and metal bioconjugates.

Selected Reading
Patra M, Gasser G, Metzler-Nolte N. Small Organometallic Compounds as Antibacterial Agents. Dalton Trans 2012, 41, 6350 - 6358; DOI: 10.1039/C2DT12460B.

Gasser G, Metzler-Nolte N. The Potential of Organometallic Complexes in Medicinal Chemistry. Curr Opinion Chem Biol 2012, 16, 84-91; DOI: 10.1016/j.cbpa.2012.01.013.

Gasser G, Sosniak AM, Metzler-Nolte N. Metal-containing peptide nucleic acid conjugates. Dalton Trans 2011, 40, 7061-7076.

Gasser G, Ott I, Metzler-Nolte N. Organometallic Anticancer Compounds. J Med Chem 2011, 54, 3-25.


Read more ...


 

meyer hemmo-webCELLULAR HOMEOSTASIS, PROLIFERATION AND STRESS RESPONSES

Prof. Dr. Hemmo Meyer

Current Position: Full Professor (W3), University of Duisburg-Essen
Group Leader: Junior Group Leader at ETH Zurich
Postdoc: Imperial Cancer Research Fund, London, and Yale University
PhD: Human Biology in Marburg, Germany

Research Interest
Cells need to cope with a multitude of stress conditions that relentlessly inflict damage to its most vital components. This includes insults to the DNA that threatens genome stability, damage of proteins that can then form toxic aggregates, or injury of whole organelles such as mitochondria and lysosomes that releases harmful components. Cells have developed sophisticated molecular responses to these stresses that maintain protein homeostasis and organelle function, and ensure genomic stability. We are interested in deciphering these responses and uncover how they counteract stress-induced cell death and aging-related degeneration, or maintain cell proliferation.

We have been working to understand how the ubiquitin-proteasome system governs these cellular stress responses with a recent focus on the role of autophagy and underlying mechanisms. The projects have relevance for understanding myodegenerative and neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia, as well as for novel approaches to cancer therapy.  Our approaches are fluorescence microscopy of tissue culture models, gene silencing and editing, imaging-based small-scale screening, biochemical and proteomic analysis. 

Techniques
-functional genomics in human tissue culture cells using RNAi
-live cell microscopy
-advanced microscopy
-proteomics
-protein biochemistry
-biochemical reconstitution in Xenopus egg extracts.


Selected Reading
Papadopoulos C, Kirchner P, Bug M, Grum D, Koerver L, Schulze N, Poehler R, Dressler A, Fengler S, Arhzaouy K, Lux V, Ehrmann M, Weihl CC, Meyer H. VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy. EMBO J, 2017, 36:135-150.

van den Boom J, Wolf M, Weimann L, Schulze N, Li F, Kaschani F, Riemer A, Zierhut C, Kaiser M, Iliakis G, Funabiki H, Meyer H. VCP/p97 extracts sterically trapped Ku70/80 rings from DNA in double strand break repair. Mol. Cell, 2016, 64: 189–198.

Meyer HH, Bug M, Bremer S. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat Cell Biol 2012, 14(2), 117-23. Review.

Ritz D, Vuk M, Kirchner P, Bug M, Schütz S, Hayer A, Bremer S, Lusk C, Baloh RH, Lee H, Glatter T, Gstaiger M, Aebersold R, Weihl CC, Meyer H. Endolysosomal sorting of ubiquitinated caveolin-1 is regulated by VCP/p97 and UBXD1 and impaired by VCP disease mutations. Nat. Cell Biol 2011, 13(9), 1116-23.

Ramadan K, Bruderer R, Spiga F, Popp O, Baur T, Gotta M, and Meyer HH. Cdc48/p97 promotes reformation of the nucleus by extracting Aurora B kinase from chromatin. Nature 2007, 450, 1258-62.

Read more ...

 


 

Musacchio Andrea CELL DIVISION IN VITRO AND IN VIVO

Prof. Dr. Andrea Musacchio

since 2011: Director, Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Phyisiology, Dortmund, Germany
1999-2010: Group Leader at the European Institute of Oncology, Milan, Italy
1995-1998: Postdoc at the Harvard Medical School, Boston
1991-1995: PhD, European Molecular Biology Laboratory and University of Heidelberg, Germany
1990: Degree in Biology from Tor Vergata University of Rome, Italy

Research Interest
Cells are the universal element of biological matter, and their division is of outmost importance for organismal development and for the propagation of life across generations. The reductional division of cells, known as meiosis, gives rise to gametes, whose encounter restores the genetic content (ploidy) of organisms. The equational division of cells, known as mitosis, provides the daughter cells with faithful copies of the genome. Both process are accurate and closely regulated. Our laboratory studies the molecular mechanisms of cell division, their regulation, and their deregulation in the most common disease of cell division, cancerous transformation. In particular, we focus on chromosome segregation and its regulation. Chromosome segregation to the daughter cells requires their prior capture by a microtubule-based structure known as the spindle. Chromosome capture starts in prometaphase and continues until all chromosomes have aligned at the metaphase plate, and it engages a structure on chromosomes known as the kinetochore. Kinetochores, which assemble on specialized centromeric chromatin, contain a large number of different proteins (>100 in humans), each in multiple copies. Our work focuses on the reconstitution and characterization of kinetochore function, using a variety of approaches ranging from structural to cell biology via detailed biochemical analysis. Our efforts have the potential to reveal the essence of crucial mechanisms that drive chromosome segregation in all eukaryotic cells. In the future, we envision our reconstituted kinetochores to become incorporated in “synthetic cells” created in the laboratory and capable of self-propagation in vitro.


Techniques
Biochemical reconstitution of protein complexes, biophysical analysis of macromolecules (e.g. calorimetry, ultracentrifugation), X-ray crystallography, electron microscopy (EM), advanced light microscopy, cell biology. We are proficient in a number of approaches of recombinant protein production (e.g. bacteria, insect cells).

Selected Reading
Basilico F, Maffini S, Weir JR, Prumbaum D, Rojas AM, Zimniak T, De Antoni A, Jeganathan S, Voss B, van Gerwen S, Krenn V, Massimiliano L, Valencia A, Vetter IR, Herzog F, Raunser S, Pasqualato S & Musacchio A. elife 2014, 3:e02978.


Krenn V, Overlack K, Primorac I, van Gerwen S & Musacchio A. KI motifs of human Knl1 enhance assembly of comprehensive spindle checkpoint complexes around MELT repeats. Curr Biol 2014, 24(1), 29-39.

Petrovic A, Mosalaganti S, Keller J, Mattiuzzo M, Overlack K, Krenn V, De Antoni A, Wohlgemuth S, Cecatiello V, Pasqualato S, Raunser S & Musacchio A. Modular Assembly of RWD Domains on the Mis12 Complex Underlies Outer Kinetochore Organization. Mol Cell 2014, 53, 591-605.

Overlack K, Krenn V & Musacchio A. When Mad met Bub. EMBO Rep 2014, 15, 326-8.

Primorac I, Weir JR, Chiroli E, Gross F, Hoffmann I, van Gerwen S, Ciliberto A & Musacchio A. Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling. elife 2013, 2:e01030.

 

Read more ...


 

HeinzNeumannINVESTIGATION OF CHROMATIN DYNAMICS WITH AN EXPANDED GENETIC CODE

Dr. Heinz Neumann

since May 2016: Group leader at Max Planck Institute of Molecular Physiology
2009-2016: Free Floater Junior Research Group Leader “Applied Synthetic Biology” and Emmy-Noether Research Group Leader at Georg August University Göttingen, Germany
2006-2009: Postdoc, MRC Laboratory of Molecular Biology, Cambridge, UK with Jason Chin
2005: PhD in Biochemistry, Universities of Tübingen and Lausanne, Switzerland with Andreas Mayer
2000: Diploma in Chemistry, Universities of Darmstadt and Tübingen, Germany with Bernd Fakler

Research Interest
The question of why and how chromosomes condense in mitosis has intrigued scientists for more than a century and remains among the greatest mysteries of cell biology. My group investigates the dynamic properties of chromatin, especially during the transition from interphase to mitosis, employing new methods developed in the field of synthetic biology. With genetically encoded UV-crosslinker amino acids we have recently discovered an inter-nucleosomal interaction that drives compaction of chromatin triggered by a signalling cascade in mitosis (Wilkins et al. Science 2014). Currently, we are expanding this approach to map the interactome of the nucleosome in living yeast with the aim to reveal the mechanistic principles of mitotic chromosome condensation.

Techniques
Incorporation of unnatural amino acids in proteins of bacteria, yeast and mammalian cells (Genetic Code Expansion)
Biochemical reconstitution of chromatin templates and their biophysical/structural characterization (e.g. FRET, EM)
Protein-Protein interaction studies (e.g. UV-crosslinking in vivo, co-IP)

Selected Reading
Kruitwagen T, Denoth-Lippuner A, Wilkins BJ, Neumann H and Barral Y. Axial contraction and short-range compaction of chromatin synergistically promote mitotic chromosome condensation. eLife 2015, DOI:10.7554/eLife.10396.

Hoffmann C and Neumann H. In vivo mapping of FACT-Histone interactions identifies a role of Pob3 C-terminus in H2A-H2B binding. ACS Chem Biol 2015, 10, 2753-63.

Wilkins BJ, Hahn LE, Heitmuller S, Frauendorf H, Valerius O, Braus GH and Neumann H. Genetically Encoding Lysine Modifications on Histone H4. ACS Chem Biol 2015, 10, 939-44.

Wilkins BJ, Rall NA, Ostwal Y, Kruitwagen T, Hiragami-Hamada K, Winkler M, Barral Y, Fischle W, and Neumann H. A cascade of histone modifications induces chromatin condensation in mitosis. Science 2014, 343, 77-80.

Neumann H. Rewiring translation - Genetic code expansion and its applications. FEBS Lett 2012, 586, 2057-2064.


Read more ...

 


Stefan Raunser webSTRUCTURAL BIOCHEMISTRY

Prof. Dr. Stefan Raunser

Current Position: Director, Department of Structural Biochemistry, Max Planck Institute of Molecular Phyisiology, Dortmund; Adjunct Professor, Faculty of Chemistry and Chemical Biology, Technical University Dortmund and Honorary Professor, Centre for Molecular Biotechnology, University Duisburg-Essen
01/2014-06/2014: Einstein-Professor for Membrane Biochemistry (W3) at Freie Universität, Berlin
2008-2013: Independent Group Leader at the Max Planck Institute of Molecular Phyisiology, Dortmund

2005-2008: Postdoc in the laboratory of Dr. T. Walz, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA
2001-2004: PhD in the laboratory of Dr. W. Kühlbrandt, MPI of Biophysics, Frankfurt
1995-2000: Studies of Biology and Chemistry at the University of Mainz and at the Nottingham Trent University, UK

Research Interest
The research of our group focuses on structural and functional studies of macromolecular complexes. In particular, we focus on sterol-sensing membrane proteins that are involved in cholesterol homeostasis, transport and synthesis. Our group uses electron crystallography and X-ray crystallography, respectively, to determine the structure of the respective membrane proteins in their near-to-native lipidic environment and at high resolution. Besides structural studies, we are exploring the function of these proteins in vivo and in vitro by biochemical and functional studies as well as by cellular assays.
Another major interest of our group is to understand the function and structural organization of bacterial toxin complexes that permeate the membrane and translocate actin-attacking enzymes into the target cell. We use a hybrid approach, including biochemical reconstitution, structural analysis by single particle cryo-EM and X-ray crystallography, fluorescence-based assays and site-directed mutagenesis to determine the structures and functions of these complexes.

Techniques
Cryo electron microscopy, cryo electron tomography, electron crystallography, membrane protein biochemistry, X-ray crystallography.


Selected Reading
Gatsogiannis C, Merino F, Prumbaum D, Roderer D, Leidreiter F, Meusch D, Raunser S. Membrane insertion of a Tc toxin in near-atomic detail. Nat Struct Mol Biol 2016 (Epub ahead of print)

von der Ecken J, Heissler SM, Pathan-Chhatbar S, Manstein DJ, Raunser S Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution. Nature 2016, 534(7609):724-8.

Friese A, Faesen AC, Huis in 't Veld PJ, Fischböck J, Prumbaum D, Petrovic A, Raunser S, Herzog F, Musacchio A. Molecular requirements for the inter-subunit interaction and kinetochore recruitment of SKAP and Astrin. Nat Commun 2016, 7:11407.

Whitney JC, Quentin D, Sawai S, LeRoux M, Harding BN, Ledvina HE, Tran BQ, Robinson H, Goo YA, Goodlett DR, Raunser S, Mougous JD. An Interbacterial NAD(P)(+) Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells. Cell 2015, 163(3):607-19.

Poepsel S, Sprengel A, Sacca B, Kaschani F, Kaiser M, Gatsogiannis C, Raunser S, Clausen T, Ehrmann M (2015) Determinants of amyloid fibril degradation by the PDZ protease HTRA1. Nat Chem Biol 2015, 11(11):862-9.

Gao M, Berghaus M, von der Ecken J, Raunser S, Winter R. Condensation Agents Determine the Temperature-Pressure Stability of F-Actin Bundles. Angew Chem Int Ed Engl 2015, 54(38):11088-92.

Raunser S, Gatsogiannis C. Deciphering the tubulin code. Cell 2015, 161(5):960-1.

Rosin C, Erlkamp M, Ecken Jv, Raunser S, Winter R. Exploring the stability limits of actin and its suptrastructures, Biophys J 2014, 107(12):2973-83.

Gatsogiannis C, Hofnagel O, Markl J, Raunser S. Structure of Mega-Hemocyanin reveals protein origami in snails, Structure 2015, 23(1):93-103.

von der Ecken J, Müller M, Lehman W, Manstein DJ, Penczek PA, Raunser S. Structure of the F-actin-tropomyosin complex, Nature 2015, 519(7541):114-7.

Meusch D, Gatsogiannis C, Efremov RG, Lang AE, Hofnagel O, Vetter IR, Aktories K, Raunser S. Mechanism of Tc toxin action revealed in molecular detail. Nature 2014, 508(7494), 61-5.


Sadian Y, Gatsogiannis C, Patasi C, Hofnagel O, Goody RS, Farkasovský M, Raunser S. The role of Cdc42 and Gic1 in the regulation of septin filament formation and dissociation. ELife 2013, 2:e01085.

Gatsogiannis C, Lang AE, Meusch D, Pfaumann V, Hofnagel O, Benz R, Aktories K, Raunser S. A syringe-like injection mechanism in Photorhabdus luminescens toxins. Nature 2013, 495(7442), 520-23.

Behrmann E, Müller M, Penczek PA, Mannherz HG, Manstein DJ, Raunser S. Structure of the rigor actin-tropomyosin-myosin complex. Cell 2012, 150(2), 327-339.

Hernandez JM, Stein A, Behrmann E, Riedel D, Cypionka A, Farsi Z, Walla PJ, Raunser S, Jahn R. Membrane fusion intermediates via directional and full assembly of the SNARE complex. Science 2012, 336(6088), 1581-4.

Bröcker C, Kuhlee A, Gatsogiannis C, Balderhaar HJ, Hönscher C, Engelbrecht-Vandré S, Ungermann C, Raunser S. Molecular architecture of the multisubunit homotypic fusion and vacuole protein sorting (HOPS) tethering complex. Proc Natl Acad Sci USA 2012, 109(6), 1991-96.

 

Read more ...