PhD 1991, Institute of Molecular Pathology, Vienna.
Joe Lewis
Postdoctoral research at EMBL.
Selected references
Group leader, Wellcome Trust Centre for Cell Biology, Edinburgh. Group and Global HCV Project Leader at Anadys Pharmaceuticals, Heidelberg. MBA 2009, Essec and Mannheim Business School. Facility head at EMBL since 2004.
Chemical Biology Core Facility Small molecules play essential roles in many areas of basic research and are often used to address important biological questions. The aim of our Chemical Biology Core Facility is to enable research groups to address biological questions by identifying and developing ‘biotool’ compounds against novel targets. We can assist groups in the development of primary and secondary assays for screening against our in-house compound library and guide them through the process of developing tool compounds for their specific target. Chemical optimisation projects can be done in collaboration with our chemistry partners. The facility is a collaboration between EMBL, the German Cancer Research Center (DKFZ), Heidelberg and the University of Heidelberg to provide the infrastructure and expertise to open up small molecule development to research groups at all three institutions.
Major projects and accomplishments The facility was established at the beginning of 2004. We have a very strong pipeline of projects from all three institutes covering biochemical and cell based targets. At the end of 2009 we established a computational chemistry as part of the facility offering. Elara Pharmaceuticals GmbH and Savira Pharmaceuticals GmbH have been founded to further develop and commercialise active compounds indentified in the facility, targeting specific cancer cell signalling pathways and the influenza virus respectively.
Services provided The new Chemical Biology Core Facility screening library is composed of 79,000 compounds. The selection focussed on compound catalogues from three leading vendors in the field. Each vendor offers access to significantly larger collections with low redundancy and highly competitive prices coupled with attractive options for resupply and follow-up synthesis services. The selected compounds were checked for drug-likeness, structural and shape diversity, novelty and compliance with medicinal chemistry requirements. Individual compound selection was done by picking representative compounds around selected scaffolds. A scaffoldbased selection offers the advantage of high information screening: since the structural space around each scaffold is covered appropriately, any hit compounds from a high-throughput screen can be rapidly followed up by selecting similar compounds to enable initial structure-activity relationships to be discerned. This will help in the prioritisation of the hit compounds for further medicinal chemistry optimisation.
Guilligay, D., Tarendeau, F., Resa-Infante, P., Coloma, R., Crepin, T., Sehr, P., Lewis, J.D., Ruigrok, R.W., Ortin, J., Hart, D.J. & Cusack, S. (2008). The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat. Struct. Mol. Biol., 15, 500-506 Polycarpou-Schwarz, M., Muller, K., Denger, S., Riddell, A. et al. (2007). Thanatop: a novel 5-nitrofuran that is a highly active, cellpermeable inhibitor of topoisomerase II. Cancer Res., 67, 44514458 Sehr, P., Pawlita, M. & Lewis, J. (2007). Evaluation of different glutathione Stransferase-tagged protein captures for screening E6/E6AP interaction inhibitors using AlphaScreen (R). J. Biomol. Screen., 12, 560-7 Lewis, J.D. (2007). The role of the chemical biology core facility at EMBL: a vision for a European roadmap. ACS Chem Biol., 2, 21-3
Further services include: •
Selection of appropriate assay technology platforms;
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Developing assays for mediumthroughput screening;
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Assisting in the design of secondary specificity assays;
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Compound characterisation;
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Managing compound acquisition through our chemistry partners;
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Computation screening using Surflex.
Parallel pipetting of samples in 384-well format.
Technology partners •
Technology partners: Perkin Elmer, IDBS, GE.
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Chemistry partners: Tripos Inc., AMRI, Chembridge and Enamine.
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