A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae.
Mol Syst Biol. 2010
At EMBL, many groups incorporate different areas of Chemistry into their research, such as chemical synthesis, spectroscopic and spectrometric methods, chemoinformatics, chemical docking and modeling, protein semisynthesis and engineering, as well as analytical and medicinal chemistry.
Chemistry often enables an understanding of biological phenomenona that are difficult to approach in a different way.
EMBL offers the unique opportunity to be involved in development and application of chemical tools (of whichever nature) to answer biological questions. Applications range from deciphering signaling pathways and ligand-macromolecule interactions to drug discovery, to name a few.
Biochemical and chemical approaches to biomolecular networks
Biological or cellular functions emerge from networks of interacting molecules. We develop and apply (bio)chemical strategies to chart interactions between biomolecules on a large-scale.
One of our recent focus concerns the development of metabolite arrays and the integration of biochemical protein purification and mass spectrometry to study interactions between proteins and small molecule metabolites.
Mol Syst Biol. 2010
Nov 27;326(5957):1263-8 PubMed
Nov 27;326(5957):1268-71. PubMed
High resolution studies of protein plasticity
For the study of biological mechanisms, protein engineering has become an essential tool. With genetically encoding non natural amino acids as our central strategy, we recruit a large plethora of novel chemical biology techniques to micro-manipulate biological function.
A particular focus is the introduction of small, minimally perturbing fluorescent probes site selectively into proteins to study molecular structure and dynamics.
J Am Chem Soc 2008
Nature Chem Biol 3 2007
J R Soc Interface 2008
Microfluidic approaches in drug discovery and personalised medicine
The Merten Group develops novel screening and synthesis approaches based on microfluidic systems. For example, we have established tailored systems for the screening of one-bead-one-compound (OBOC) libraries.
In parallel, we are developing microfluidic modules for on-chip combinatorial synthesis of highly diverse compound libraries (e.g. making use of click chemistry reactions).
Compared to conventional approaches, this should result in drastically increased throughput and minimized consumables costs. Hence large areas of chemical structure space can be explored in search of new bioactive molecules. For this purpose we also develop novel assays coupling a desired chemical or biological property with a positive fluorescence signal.
Chem Biol. 2010
Chem Commun (Camb) 2010
Apr 7;46(13):2209-11. Epub 2010 Feb 23 (selected as a "Hot Paper")
J Am Chem Soc. 2009
Structural biology of macromolecular complexes
The Wilmanns Group is interested in structural/functional relations of protein targets of biomedical relevance. For some of our targets, we are interested to identify small molecule inhibitors, either to modulate enzymatic activity or to interfere with assembly processes.
Our approach is either by experimental compound screening or by structure-based in silico screening, followed by assay-based refinement of promising compounds using medicinal chemistry. Examples in recent research are on targets from Mycobacterium tuberculosis, protein kinases and a number of transcription factors.
Curr Protein Pept Sci. 2007
Proc Natl Acad Sci USA 2006