P03 - Identification and significance of sulfur mustard-induced TRP channel modifications
Transient Receptor Potential (TRP) channels are considered to play a pivotal role in the detection of TIH, in the control of adaptive responses, and in the initiation of detrimental signaling cascades.
TRPA1 can be activated by a plethora of reactive, electrophilic toxic compounds via covalent modification of cysteine residues.
The chemical warfare agent sulfur mustard (SM) is able to activate TRPA1 channels and inhibition of TRPA1 prevented noxious effects of SM in vitro.
However, the exact mechanism of TRPA1 activation by SM and related substances remains unclear until now.
The candidate will use TRP channel (e.g. TRPA1, TRPV4) overexpressing cell system, generate functional mutations thereof and characterize the cells (e.g. calcium imaging, cell viability).
Moreover, mass spectrometry analysis (LC-ESI MS/MS or MALDI-TOF MS/MS) will be conducted to investigate the interaction of SM with specific amino acid residues of the respective TRP channels.
Prof. Dr. med. Horst ThiermannBundeswehr Institute of Pharmacology and Toxicology and Technical University of Munich +49 89 992692 2925 |