Helmholtz Zentrum München - HMGU
Structural biology at Helmholtz Zentrum München
As a leading center in health research Helmholtz Zentrum München (HMGU) aims to preserve and improve the health of individuals by developing innovative strategies for diagnosis, treatment and prevention. To achieve these goals innovative methods in biomedical research are being developed and applied.
The Institute of Structural Biology at HMGU studies the spatial structures and molecular interactions of biological macromolecules, i.e. proteins, nucleic acids (RNAs and DNA) and their complexes. The detailed structural information forms a basis to understand molecular mechanisms of cellular processes and disease-linked pathways.
Researchers in the institute employ integrated structural biology methods to obtain a more complete description of the structure and dynamics of biological molecules in solution. 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.
The structural information provides an understanding of the molecular mechanisms of basic cellular pathways, and of molecular processes linked to human disease. Our studies focus on fundamental processes in the regulation of gene expression, cellular signal transduction and peroxisome biogenesis. In order to tackle large protein complexes and fibril structures, we develop and improve novel experimental techniques based on solution- and solid-state NMR. The molecular mechanisms studied are implicated in various diseases, such as neurodegenerative disorders, diabetes and cancer.
The structural data provide a basis for the rational drug design and the development of small molecule inhibitors as novel bioactive compounds. Thus, the results of our structural research is used to rationally guide the development of such molecules for therapeutic applications, also in the context of the CPA Helmholtz Wirkstoffforschung.
Publications
Hennig J, Militti C, Popowicz GM, Wang I, Sonntag M, Geerlof A, Gabel F, Gebauer F, Sattler M
Structural basis for the assembly of the Sxl–UNR translation regulatory complex
(2014) Nature, 515:287-90 [Pubmed] [Press release (Helmholtz)]
Schlundt A, Heinz GA, Janowski R, Geerlof A, Stehle R, Heissmeyer V, Niessing D, and Sattler M
Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation.
(2014) Nat Struct Mol Biol 21, 671-8. [Pubmed] [press release]
Schilling F, Warner LR, Gershenzon NI, Skinner TE, Sattler M, Glaser SJ.
Next-Generation Heteronuclear Decoupling for High-Field Biomolecular NMR Spectroscopy.
(2014) Angew Chem Int Ed Engl. Mar 12. doi: 10.1002/anie.201400178 [Pubmed]
Mackereth CD, Madl T, Bonnal S, Simon B, Zanier K, Gasch A, Rybin V, Valcarcel J, and Sattler M
Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF.
(2011) Nature 475, 408-11 [Pubmed] [Pressemitteilung Helmholtz Zentrum München]
Research Groups
- Michael Sattler - Molecular recognition in the regulation of gene expression and signaling
Solution state NMR, SAXS, SANS, integrated structural biology - Dierk Niessing - RNA localization and intracellular transport
Crystallography - Bernd Reif - Solid-state NMR of amyloids and membrane proteins
Solid-state NMR spectroscopy - Igor Tetko - Chemoinformatics & Chemical Biology
Chemoinformatics - Tobias Madl - Structural Biology of Signal Transduction
Solution state NMR Spectroscopy, SAXS, SANS, integrated structural biology - Franz Hagn - Structural Membrane Biochemistry
multidimensional NMR spectroscopy, electron microscopy, X-ray crystallography
Infrastructure and unique expertise
- Bayerisches NMR Zentrum http://www.bnmrz.org
- Small X-ray Scattering (bench top instrument at TU München/SFB1035)
- Small Angle Neutron Scattering (collaborations with MLZ/TU München & ILL Grenoble)
Training
- EMBO Course Biomolecular NMR Spectroscopy at BNMRZ, Jul/Aug 2015
- G-NMR Teaching School in Basics of NMR Spectroscopy at BNMRZ Oct 2014
