Screening Unit
Introduction
- 384tip pipetting systems enable one to test up to 20.000 compounds per day for their biological effects.
- Cytotoxic potential of compounds identified by fluorescent staining of cellular structures. Light blue nuclei mark cells with damaged membranes, while red fluorescence marks functional mitochondria.
The FMP hosts the central open access technology platform of the ChemBioNet and NDDD network, the Screening Unit. The Unit was set up in 2003 for systematic screening of large compound libraries with state-of-the-art equipment for process automation and detection systems. The mission of the Unit is to identify bioactive small molecules as tools for modulation of biological functions for research termed Chemical Biology. More then 130 screening projects have been already supported in EU, BMBF, DFG and TSB/IBB funded work, together with academic and pharmaceutical industry partners.
Data documentation and analysis has been automated according to defined standard operating procedures and analysis pipelines. About 32.000 compounds can be screened (per pipetting workstation, total of 4) and analyzed in a single day (12 hrs) depending on test system/detection method. A complex set of reports containing heat maps, different statistical analysis routines, similarity clustering and inter screen analysis for identification of frequent hitters has been established.
Furthermore the Screening Unit tests novel detection systems and in the case of positive outcomes integrates these into the daily screening service. For instance the usage of machine learning routines in collaboration with the ETH-Zürich for automated object identification in screening with automated microscopes. The latest technology integrated is the label-free impedance measurement technology (see also under "Technologies" for more detail).
Beside this service, 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 to be used for Systems Biology in C. elegans, mouse and in human cell lines.
As genome-wide RNA-interference may require to screen 800 MTP´s in 384well format, it is a very expensive approach, especially in combination with dual-luciferase reporters, plus costs for transfection reagents. Therefore you may wish to contact us to estimate the required funding budgets.
Compound Collections
- Liquid transfer with 384-tip head.
- Robotic manipulator places 96-tube rack on cap removing module.
The Screening Unit manages the central compound collection of the ChemBioNet (about 30.000 cpds) and several in-house collections (total of 64.000 cpds) in Remp-SSS- and Liconic-KIWI storage systems combined with a FreedomEvo pipetting system (Tecan). The automated storage systems provide a capacity for about 136.000 cpds in duplicate with a total number of about 272.000 tubes stored at -20° C. The Unit actively collects compound collections from academic chemists and currently holds about 6.000 cpds (see also under "Compound Management" or "Downloads" for more detail) .
The ChemBioNet collection of commercially available compounds has been financed by the FMP in cooperation with the Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch (MDC), the Helmholtz-Zentrum für Infektionsforschung (HZI), the Biotechnology Centre of Oslo, University of Oslo, and the University of Konstanz. The design and selection of compounds is based on a maximum common substructure analysis of the World Drug Index (WDI).
The project-oriented chemical synthesis and optimization of small molecules is supported by medicinal chemists, drug modellers and structural biologists at the Institute on the basis of individual cooperations.
