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Molecular Targets and Therapeutics Center Institute of Structural Biology

From the biggest building to the smallest molecule, the function of an object is determined by its structure. It is impossible to accurately determine and understand how the object works without discovering its structure. The Institute of Structural Biology investigates the spatial structures of biological macromolecules, i.e. proteins, nucleic acids (RNAs and DNA) and their complexes. These structural data help us to understand molecular mechanisms of cellular processes and disease-linked pathways.

From the biggest building to the smallest molecule, the function of an object is determined by its structure. It is impossible to accurately determine and understand how the object works without discovering its structure. The Institute of Structural Biology investigates the spatial structures of biological macromolecules, i.e. proteins, nucleic acids (RNAs and DNA) and their complexes. These structural data help us to understand molecular mechanisms of cellular processes and disease-linked pathways.

About our research

We are using and developing modern solution- and solid-state NMR- spectroscopy techniques as well as X-ray crystallography to elucidate the structural details of complex biomolecules. These data are combined with complementary information from Small Angle X-ray and/or Neutron Scattering (SAXS/SANS), and biophysical techniques (i.e isothermal titration calorimetry, static and dynamic light scattering) to describe the structure-function relationships of biomolecules. Computational methods provide additional insight in the cases where obtaining precise experimental data is difficult.

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Research Groups

Molecular recognition in the regulation of gene expression and signaling

We are using nuclear magnetic resonance (NMR) spectroscopy in integrative structural biology, combined with X-ray crystallography, SAXS, SANS, cryo-EM and biophysical techniques to study the structure, interactions and dynamics of biomolecules in solution and for structure-based drug discovery.

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Solid state NMR of amyloids and membrane proteins

Our group is interested in the structural characterization of biomolecules using MAS solid-state and solution-state NMR spectroscopy, with focus on amyloidogenic peptides and proteins, and membrane proteins. Our research is divided into the areas 1) Understanding of the mechanisms that lead to protein aggregation at atomic resolution, 2) Investigation of large protein complexes that are not amenable by solution-state NMR or crystallography, 3) Membrane protein structure and 4) Development of methods in solid-state NMR for quantification of structure and dynamics of biomolecules.

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RNA localization and intracellular transport

Our main interest is to understand principles of RNA-mediated gene regulation and its contribution to pathologies. Our research tools include structural biology and biophysics, RNA and protein biochemistry as well as various aspects of cell biology.

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Structural Membrane Biochemistry

We aim at characterizing the structure, dynamics, small molecule and partner protein interactions of selected membrane protein systems to obtain essential insights on their functionality and to facilitate rational drug design approaches.

Our main tool to achieve this goal is nuclear magnetic resonance (NMR) spectroscopy. In order to be able to study membrane proteins in a native lipid environment we develop novel and advanced membrane mimetics, called phospholipid nanodiscs, for their use in biochemical, biophysical and structural studies.

We work on biologically important systems, such as mitochondrial membrane proteins, G-protein coupled receptors (GPCRs) and their associated G-proteins and metabolite transporters in plants. These membrane proteins are involved in metabolic diseases, neurological disorders and cancer, or supply energy to enable plant growth and the generation of biomass. Beside NMR, we use electron microscopy, X-ray crystallography and a variety of other biophysical, biochemical and computational methods.

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Structure Based Drug Discovery

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Informatics & Chemical Biology

Chemoinformatics & Chemical Biology group develops computational tools for drug discovery, including Virtual Computational Chemistry Laboratory (VCCLAB) www.vcclab.org and On-line CHEmical Modeling Environment (OCHEM) ochem.eu in close collaboration with its spin-off company BIGCHEM GmbH (https://bigchem.de/).

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Therapeutic Antibodies

Tumor-specific monoclonal antibodies

Antibody-based therapy of cancer is one of the most important success stories of personalized medicine. Although the concept that antibodies could serve as 'magic bullets' in the treatment and detection of cancer has a long history, the number of available antibodies is still too small. A key challenge for the development of new therapeutic antibodies for the clinic is the identification of suitable and accessible target molecules on the surface of cancer cells. We pursue a proprietary approach for the generation and evaluation of novel antibodies with a potential for cancer treatment and detection.

Development of a new experimental therapy for Glioblastoma

Glioblastoma multiforme (GBM) is the most common and most aggressive type of brain cancer with a dismal prognosis. As a first translational project, we develop a new experimental immunotherapy for the treatment of glioblastoma. This approach is based on our antibody 6A10 that binds to an enzyme present on the surface of glioblastoma cells but not of normal brain. Equipped with a radioactive payload, the antibody will be injected into the hole that remains after surgical removal of the tumor. From there, the antibody will migrate into the surrounding brain tissue. If it encounters a residual cancer cell, it will bind to this cell and – hopefully – destroy it. Resident tumor cells that remained in the brain after surgery are the origin of recurrent disease, and our approach aims at significantly prolonging recurrence-free survival.

Spin-off company 'Eximmium'

We are actively pursuing the commercialization of our proprietary therapeutic antibody candidates. Eximmium will concentrate on the generation and pre-clinical validation of proprietary first-in-class antibodies. Currently, we are talking with various potential investors.

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The Protein Expression and Purification Facility was established in fall 2009 to help researchers at Helmholtz Zentrum München to quicker and better produce recombinant proteins. To achieve this goal the PEPF will provide support and training, materials and facilities for the cultivation of bacteria and insect cells and for the purification and biochemical and biophysical characterization of proteins.

The PEPF will also produce recombinant proteins for general use (i.e. proteases and polymerases) and, in collaboration with individual researchers, specific proteins for a wide range of applications, including structural and functional studies, small ligand screening and antibody production.

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The implementation of a Macromolecular Crystallography Platform at the STB is an important structural biology technology on campus. Currently, the platform is equipped with a Mosquito crystallization robot for high throughput automated screening of crystal growth in 96-well format and volumes as small as 200 nL. Routinely, up to thousand different crystallization conditions are screened with wide ranges of buffers and precipitating agents. Once initial crystals are obtained, the optimization process starts with automated or manual mode to obtain isolated crystals of sufficient dimensions and quality for the X‑ray diffraction experiments.

For x-ray diffraction experiments and data collection, we have regular access to the P11 beamline at Deutsches Elektronen Synchrotron (DESY) of the Helmholtz Association in Hamburg and to the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. The platform has all required hard- and software as well as know-how for data processing, structure solving, refinement, and analysis. For drug discovery, the Facility provides high-resolution structures of inhibitors bound to their targets, allowing for their structure-based, rational optimization. Thus, it complements and strengthens existing drug discovery efforts at HMGU. Furthermore, the platform expands the methodology available to understand the mechanistic basis for biological processes.

The platform is established and run by the Niessing lab at the Institute of Structural Biology. Dr. Robert Janowski is the X-ray crystallography expert who manages the platform. Please contact us for more details.

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Scientists at Our Institute

Prof. Dr. Michael Sattler

Head of Molecular Targets and Therapeutics Center, Director of Structural Biology View profile

Latest Publications of Our Institute

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Contact

Institute Office

Karen Biniossek

Assistant to Prof. Dr. Michael Sattler

TUM Garching, BNMRZ