TRP (Transient receptor potential) channels are a superfamily of cation channels that play critical roles in sensory physiology, contributing to processes as diverse as vision, olfaction, pain, mechano- and thermosensation. They are activated by a variety of stimuli and enable cells and organisms to adapt to their local environment. For the TRPN channels, one of the seven subfamilies of TRP channels, neither the detailed structure nor their molecular function is understood. This is also due to a lack of selective inhibitors for TRPN channels.
In this project, TRPN channels will be analyzed on a functional and molecular level by screening for and applying specific inhibitors. Existing and exclusively synthesized libraries of the ComPlat group (KIT) will be screened for their influence on mechanosensation in hydras by the Özbek group in Heidelberg. In Hydra, TRPN channels are exclusively involved in the discharge of the stinging organelle offering a simple functional readout by monitoring prey capture. The results of the primary screens will be directly used by the chemical researchers for the syntheses of middle-sized libraries of the most interesting compound classes to enable detailed investigations on the mandatory activity-inducing moieties. The primary prey capture screen with hydras will be completed by a morphological and toxicology screen of all given compounds to enable an overview of the effects of the small molecules.
All data will be entered into a new database that will exclusively be installed for HEIKA researchers. On the basis of this database that covers all collaborative experiments that have been performed with small molecules, we will be able to compare the results of this project and following ones. Conclusions of the investigations of the same target as well as comparative studies with others (e.g. zebrafish) will elucidate the influence of the given small molecules on different species.