Chemistry: Groups beta

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.


Gavin Group (Visiting)

Biochemical and chemical approaches to biomolecular networks

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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.

Selected publications

A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae.

Gallego, O., Betts, M.J., Gvozdenovic-Jeremic, J., Maeda, K., Matetzki, C., Aguilar-Gurrieri, C., Beltran-Alvarez, P., Bonn, S., Fernandez-Tornero, C., Jensen, L.J., Kuhn, M., Trott, J., Rybin, V., Muller, C.W., Bork, P., Kaksonen, M., Russell, R.B. & Gavin, A.C.

Mol Syst Biol. 2010

Nov 30;6:430

Impact of genome reduction on bacterial metabolism and its regulation.

Yus, E., Maier, T., Michalodimitrakis, K., van Noort, V., Yamada, T., Chen, W.H., Wodke, J.A., Guell, M., Martinez, S., Bourgeois, R., Kuhner, S., Raineri, E., Letunic, I., Kalinina, O.V., Rode, M., Herrmann, R., Gutierrez-Gallego, R., Russell, R.B., Gavin, A.C., Bork, P. & Serrano, L.

Science 2009

Nov 27;326(5957):1263-8 PubMed

Transcriptome complexity in a genome-reduced bacterium.

Guell, M., van Noort, V., Yus, E., Chen, W.H., Leigh-Bell, J., Michalodimitrakis, K., Yamada, T., Arumugam, M., Doerks, T., Kuhner, S., Rode, M., Suyama, M., Schmidt, S., Gavin, A.C., Bork, P. & Serrano, L.

Science 2009

Nov 27;326(5957):1268-71. PubMed

Proteome organization in a genome-reduced bacterium.

Kühner S., van Noort V., Betts M.J., Leo-Macias A., Batisse C., Rode M., Yamada T., Maier T., Bader S., Beltran-Alvarez P., Castaño-Diez D., Chen W.H., Devos D., Güell Cargol M., Norambuena T., Racke I., Rybin V., Schmidt A., Yus E., Aebersold R., Herrmann R., Böttcher B., Frangakis A.S., Russell R.B., Serrano L., Bork, P. and Gavin, A.C.

Science 2009

326, 1235-1240


Lemke Group (Visiting)

High resolution studies of protein plasticity

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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.

Selected publications

General and Efficient Method for the Site-Specific Dual-Labeling of Proteins for Single Molecule Fluorescence Resonance Energy Transfer.

Brustard EM, Lemke EA, Schultz PG, Deniz AA, A

J Am Chem Soc 2008

52,17664-5

Control of protein phosphorylation with a genetically encoded photocaged amino acid.

Lemke EA, Summerer D, Geierstanger B, Brittain S, Schultz PG

Nature Chem Biol 3 2007

769-772

Single-molecule biophysics: at the interface of biology, physics and chemistry.

Deniz AA, Mukhopadhyay S, Lemke EA

J R Soc Interface 2008

5(18), 15-45


Merten Group (Visiting)

Microfluidic approaches in drug discovery and personalised medicine

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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.

Selected publications

Miniaturization and Parallelization of Biological and Chemical Assays in Microfluidic Devices.

Vyawahare, S., Griffiths, A.D. & Merten, C.A.

Chem Biol. 2010

Oct 29;17(10):1052-65

Nanoliter plates--versatile tools for the screening of split-and-mix libraries on-bead and off-bead.

Upert, G., Merten, C.A. & Wennemers, H.

Chem Commun (Camb) 2010

Apr 7;46(13):2209-11. Epub 2010 Feb 23 (selected as a "Hot Paper")

Imaging of mRNA in live cells using nucleic acid-templated reduction of azidorhodamine probes.

Pianowski, Z., Gorska, K., Oswald, L., Merten, C.A. & Winssinger, N.

J Am Chem Soc. 2009

May 13;131(18):6492-7


Wilmanns Group

Structural biology of macromolecular complexes

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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.

Selected publications

Bimolecular fluorescence complementation in structural biology.

Song YH, Wilmanns M.

Methods 2008

Jul;45(3):219-22

Structure-based approaches to drug discovery against tuberculosis.

Holton SJ, Weiss MS, Tucker PA, Wilmanns M.

Curr Protein Pept Sci. 2007

Aug;8(4):365-75

The Mycobacterium tuberculosis LipB enzyme functions as a cysteine/lysine dyad acyltransferase.

Ma Q, Zhao X, Nasser Eddine A, Geerlof A, Li X, Cronan JE, Kaufmann SH, Wilmanns M.

Proc Natl Acad Sci USA 2006

Jun 6;103(23):8662-7

Chemistry

From microscopy to mycology, from development to disease modelling, EMBL researchers cover a wide range of topics in the biological sciences.