Common Chemical Biology Platform (CCBP)
Our research and service group operates at the interface of chemistry and biology and provides a common chemical biology platform in support of other research groups at the institute. Essentially, we assist in systematic searches for bioactive chemicals to generate new tools for biological discovery. Small molecules are powerful tools for studying biological systems as evident from the frequent application of potent and selective inhibitors of enzymes or other biological processes such as transcription, translation, protein degradation, etc. However, in contrast to animal systems, which are nurtured from drug research, screening for novel bioactive small molecules in plant systems is a largely underdeveloped research area, despite the fact that such screens bear great potential for generating new tools for dissecting diverse biological processes. In particular, when small molecules are integrated into genetic strategies (thereby defining chemical genetics), they may help to circumvent inherent problems of forward genetics, such as redundancy or lethality of gene functions, because they can be applied in a conditional, dose-dependent and reversible manner.
Essentially, a successful chemical genetic screen comprises three equally important steps, which require specific attention and optimization to exclude pitfalls:
1. For the actual screening process it is essential to establish a reliable, robust and quantitative (or semi-quantitative) readout, which allows distinguishing between potent and less potent compounds.
2. Bioactive compounds originating from the initial screen need to be critically evaluated (e.g. by comparing their effect on a variety of biological responses and establishing EC50/IC50 values) to identify chemicals that are highly selective for a given response. If possible, the structure-function-relationship should also be established at this stage, which will require a minimum of chemical expertise.
3. Ultimately, the identification of the protein target of a small bioactive molecule is of fundamental importance for understanding its mode of action. For this, various strategies can be applied, ranging from biochemical affinity labeling to genetic screening, depending on the nature of the identified compound. This stage will most likely require the co-operation with experts in chemical synthesis; we have a number of well-established contacts to external groups.
Based on the experience obtained from various chemical screening campaigns (see Previous screens), we can assist in designing, performing and evaluating any new screening approach aiming at identification of small bioactive molecules, as well as outlining strategies for target identification. Additional benefits are gained from sharing common resources (chemical libraries) and efficient use of the respective equipment (see Instruments and technologies).