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Daniel Gehrlach
Anatomical and functional characterization of the mouse insular cortex
RG: Nadine Gogolla

Daniil Markov
Involvement of cerebellar Purkinje cells in adaptive locomotion of larval zebrafish
RG: Ruben Portugues


 

MPIB scientists have contributed to deciphering the 3D structure of the nuclear pore of baker's yeast cells.

Research group leader Boris Pfander and his team from the Max Planck Institute of Biochemistry, together with colleagues from the Max Planck Institute of Biophysics in Frankfurt am Main and the EMBL in Heidelberg, have investigated the 3D structure of nuclear pores in budding yeast (Saccharomyces cerevisiae). Their results, published in Nature, reveal the architecture of the nuclear pore complex in intact cells and broaden our understanding of crucial processes in life.

Nuclear pores are a highly complex assembly of proteins. Hundreds of them are embedded in the double membrane that surrounds and protects the cell’s nucleus. They act as a gateway that regulates the entry and exit of molecules. An important function of nuclear pores is to regulate the export of a molecule called messenger RNA (mRNA) from the nucleus into the surrounding cell – the cytoplasm – where it delivers instructions for the assembly of proteins. Revealing the architecture Now the scientists appreciate better how the nuclear pore works in its native context, how it is maintained and recycled. The study provides a detailed structural description of the three protein rings that make up the nuclear pore, known as the cytoplasmic, nuclear, and inner rings. To show how these rings are arranged in cells, the researchers used a combination of cell biology, computational modelling, and in-cell cryo-electron tomography: an imaging technique, that is used to produce high-resolution 3D views of the molecular landscape inside a cell. This led to fundamental new insights. The scientist found out that the 3D configuration of the cytoplasmic ring accommodates the path of mRNA export.

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Eklund, A.S., Ganji, M., Gavins, G., Seitz, O., and Jungmann, R.
Nano Lett, 2020, [Epub ahead of print].
doi: 10.1021/acs.nanolett.0c02620

Peptide-PAINT Super-Resolution Imaging Using Transient Coiled Coil Interactions

Super-resolution microscopy is transforming research in the life sciences by enabling the visualization of structures and interactions on the nanoscale. DNA-PAINT is a relatively easy-to-implement single-molecule-based technique, which uses the programmable and transient interaction of dye-labeled oligonucleotides with their complements for super-resolution imaging. However, similar to many imaging approaches, it is still hampered by the subpar performance of labeling probes in terms of their large size and limited labeling efficiency. To overcome this, we here translate the programmability and transient binding nature of DNA-PAINT to coiled coil interactions of short peptides and introduce Peptide-PAINT. We benchmark and optimize its binding kinetics in a single-molecule assay and demonstrate its super-resolution capability using self-assembled DNA origami structures. Peptide-PAINT outperforms classical DNA-PAINT in terms of imaging speed and efficiency. Finally, we prove the suitability of Peptide-PAINT for cellular super-resolution imaging by visualizing the microtubule and vimentin network in fixed cells.


Ralf Jungmann, Research Group Leader at the Max Planck Institute (MPI) of Biochemistry and Professor for Experimental Physics at the LMU Munich, together with Maartje Bastings, Director of the Programmable Biomaterials Laboratory (PBL) in the EPFL School of Engineering (STI), and Ian Parish from the University of Melbourne and Peter MacCallum Cancer Centre in Melbourne, have received 1.5 million euros in research funding from the Volkswagen Foundation. The joint project of the three research groups, funded through the initiative ”Life? – A Fresh Scientific Approach to the Basic Principles of Life” from the Volkswagen Foundation, is aimed at unraveling the origin of multicellular life. The evolution of complex multicellular organisms 600 million years ago required sophisticated cell-cell communication systems to coordinate growth, differentiation, and tissue organization. This evolutionary leap is thought to have required a fundamental change in protein organization at the key interface for intercellular communication: the cell surface.

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graduationCongratulations on your PhD!


Jennifer Wells
Structural and Functional Analysis of Transitionally Inactive Eukaryotic Ribosomes:
Regulation of Hibernation with Lso2/CCDC124 and Stalling on the Fungal Arginine
Attenuator Peptide
RG: Roland Beckmann

 


 

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Varga, J., Nicolas, A., Petrocelli, V., Pesic, M., Mahmoud, A., Michels, B.E., Etlioglu, E., Yepes, D., Häupl, B., Ziegler, P.K., Bankov, K., Wild, P.J., Wanninger, S., Medyouf, H., Farin, H.F., Tejpar, S., Oellerich, T., Ruland, J., Siebel, C.W., and Greten, F.R.
J Exp Med, 2020, 217.
doi: 10.1084/jem.20191515

AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer

Recently, a transcriptome-based consensus molecular subtype (CMS) classification of colorectal cancer (CRC) has been established, which may ultimately help to individualize CRC therapy. However, the lack of animal models that faithfully recapitulate the different molecular subtypes impedes adequate preclinical testing of stratified therapeutic concepts. Here, we demonstrate that constitutive AKT activation in intestinal epithelial cells markedly enhances tumor invasion and metastasis in Trp53ΔIEC mice (Trp53ΔIECAktE17K) upon challenge with the carcinogen azoxymethane. Gene-expression profiling indicates that Trp53ΔIECAktE17K tumors resemble the human mesenchymal colorectal cancer subtype (CMS4), which is characterized by the poorest survival rate among the four CMSs. Trp53ΔIECAktE17K tumor cells are characterized by Notch3 up-regulation, and treatment of Trp53ΔIECAktE17K mice with a NOTCH3-inhibiting antibody reduces invasion and metastasis. In CRC patients, NOTCH3 expression correlates positively with tumor grading and the presence of lymph node as well as distant metastases and is specifically up-regulated in CMS4 tumors. Therefore, we suggest NOTCH3 as a putative target for advanced CMS4 CRC patients.


graduationCongratulations on your PhD!


Itika Saha
Role of Valosin-containing protein (VCP) in tau disaggregation in mammalian cells
(Cellular characterization of polymorphic tau aggregates)
RG: F.-Ulrich Hartl

Francesca Pinci
Tumor necrosis factor (TNF) is a necroptosis-associated alarmin
RG: Veit Hornung

 


 

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Blessing, C., Knobloch, G., and Ladurner, A.G.
Curr Opin Struct Biol, 2020, 65, 130-138.
doi: 10.1016/j.sbi.2020.06.008

Restraining and unleashing chromatin remodelers - structural information guides chromatin plasticity

Chromatin remodeling enzymes are large molecular machines that guard the genome by reorganizing chromatin structure. They can reposition, space and evict nucleosomes and thus control gene expression, DNA replication and repair. Recent cryo-electron microscopy (cryo-EM) analyses have captured snapshots of various chromatin remodelers as they interact with nucleosomes. In this review, we summarize and discuss the advances made in our understanding of the regulation of chromatin remodelers, the mode of DNA translocation, as well as the influence of associated protein domains and remodeler subunits on the specific functions of chromatin remodeling complexes. The emerging structural information will help our understanding of disease mechanisms and guide our knowledge toward innovative therapeutic interventions.


graduationCongratulations on your PhD!


Katarzyna Jonak
Dynamical modeling of the network controlling meiotic divisions
RG: Wolfgang Zachariae

Sriyash Mangal
Elucidating Novel Regulators of Cytokinesis
RG: Barbara Conradt/Esther Zanin