Welcome to the 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.
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, in combination with chemical biology approaches, provide a basis for the rational design and development of small molecule inhibitors and novel bioactive compounds. We use the results of our structural research to rationally guide the development of such molecules with a potential therapeutic use.
The Institute of Structural Biology is formed of different groups with complementary research focus and provides service facilities for researchers at the Helmholtz Zentrum München and beyond. While each research group has its own unique research program, an interdisciplinary approach to structural biology research and tight internal cooperation is emphasized.
Michael Sattler is the Director of the Institute of Structural Biology and also holds the Chair of Biomolecular NMR-Spectroscopy at the Technische Universität München. He also directs the Bayerische NMR Zentrum (BNMRZ). His research focuses on molecular mechanism in the regulation of gene expression at the level of RNA and cellular signaling using solution NMR and complementary techniques, as well as structure-based drug discovery.
The group of Dierk Niessing is specialized in X-ray crystallography. The group explores the molecular principles underlying cargo recognition by molecular transport complexes, complex assembly and activation, and eventually disassembly after the transport.
In 2010, Bernd Reif was appointed as Professor of Solid-state NMR-Spectroscopy at the TU Munich and affiliated to the Institute of Structural Biology. With his expertise we can now study the structural basis of amyloids and amorphous/microcrystalline biological macromolecules, which play crucial roles in neurodegenerative diseases and diabetes.
The Emmy-Noether-funded research group of Oliver Lange joined the Institute of Structural Biology in 2011. His group employs computational structural biology methods to study the structure and dynamics of proteins using structural modeling package ROSETTA. One focus is the combination of NMR data with ROSETTA for structure determination of large protein complexes in solution.
Tobias Madl joined the institute in 2012 as an Emmy-Noether research group leader. His group investigates the structural biology of transcriptional regulation linked to human diseases. The group combines NMR data with small angle X-ray/neutron scattering experiments to characterize the structure and dynamic of large regulatory complexes.
The Chemoinformatics & Chemical Biology group, led by Igor Tetko, develops computational tools for drug discovery. Its expertise covers development of Quantitative Structure-Property Relationships (QSPR) models to predict physico-chemical and biological activity of molecules and use of a large set of linear and non-linear machine learning methods to address chemical data of different complexity and nature.
Facilities and Platforms
The Protein Expression and Purification Facility (PEPF) was established in 2010 to provide expertise and resources for sample preparation and producing proteins for structural studies, chemical biology and drug discovery.
The Fragement-based screening facility uses and develops high throughput NMR techniques to screen chemical libraries for biologically active small molecules – potential drug candidates. It also provides in vitro assaying and validation service for drug discovery projects realized in the Helmholtz Zentrum München.
In Fall 2012, a X-ray crystallography platform for biological macromolecules has been established. The platform provides help in crystalization, crystall handling and structure determination. Besides solving structures of proteins and larger co-complexes, the platform is used to perform structure-guided improvement of potential drug candidates.