Technology platform serving also for external screening projects

Leibniz-Institut für Molekulare Pharmakologie, FMP
Max-Delbrück-Campus, MDC (Berlin-Buch)

The FMP hosts the central technology platform of the ChemBioNet and NDDD network, the Screening Unit, which has been established for systematic screening of large compound libraries for bioactive small molecules modulating biological networks. The Screening Unit also manages the technology platform of the Max-Delbrueck-Centrum for Molecular Medicine (MDC) and Berlin Institute for Medical Systems Biology for genome-wide RNA-interference used for Systems Biology in C. elegans and in human cell lines.

The Screening Unit manages the central compound collection of the German Initiative for Chemical Biology, ChemBioNet, which encompasses about 50,000 substances so far. Thereof, 17.000 commercially available compounds have been chosen by the FMP in cooperation with the Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch (MDC) and the Helmholtz-Zentrum für Infektionsforschung (formerly Gesellschaft für Biotechnologische Forschung, GBF, Braunschweig) according to the guidelines of the World Drug Index (WDI). Another 20.000 compounds originate from the FMP and the Combinature Biopharm AG. Next to small molecule libraries, the FMP serves customised peptide libraries. The project oriented chemical synthesis and optimisation of small molecules is supported by medicinal chemists, drug modellers and structural biologists of the institute on the basis of individual cooperations.

The unit offers HTS/HCS on an industrial scale as a service to academic research groups, biotech and pharmaceutical companies as well as technical help with assay development and assay miniaturisation (384-well format). Currently the unit serves

• 2 ArrayScan® HCS Readers (Cellomics), automated fluorescence microscopic imaging systems designed for high content screening and high content analysis at the level of individual cells within an assay well. One ArrayScan® is embedded in an automated cell culture and liquid handling system (FreedomEvo, Tecan AG) which allows a 30-days performance. The instrument uses iterative auto-focussing to acquire images of each well, which are subsequently converted into numeric data that capture changes in cell size, shape, fluorescence intensity, and other properties.
• a Caliper LabChip® 3000 Platform which runs mobility shift enzymatic assays on sipper chips which allow automated sampling from 96- or 384-well plates and the parallel processing of up to 12 samples at a time. Since product and substrate are electrophoretically separated, interferences are reduced to a minimum resulting in high data quality.
• 3 Microplate Readers (Tecan) for the detection of either a continuous spectrum of light (fluorescence intensity, absorption, continuous range of wavelengths) or defined wavelengths (fluorescence polarisation, luciferase assays, real-time kinetics, luminescence, chemiluminescence).

The Screening Unit will not require commitments in terms of intellectual property relating to a screening project - instead investigators will be charged a fee for access to the facility. Agreements between the Screening Unit and investigators require the submission of screening results to the ChemBioNet database, after publication or patent submission.