Identification and functional characterization of ion channel-multiprotein complexes involved in nociception

• Applicant: Professorin Dr. Manuela Schmidt
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 187466051

Chronic pain imposes substantial challenges, as it is unmanageable with current pain treatments. In addition, pain therapeutics target molecules with key physiological functions and therefore elicit severe side effects. In the light of these difficulties, identification of molecules and associated protein scaffolds, which are selectively expressed or enriched in primary nociceptive neurons, is highly desirable. In these neurons, TRPA1 and TRPV1 channels serve as noxious stimulus detectors and, therefore, represent primary targets for pain research. Despite intensive study of TRPA1 and TRPV1, little is known about the composition of their protein scaffold, especially during pain states. The goal of this proposal is to identify and study multiprotein complexes associated with TRPA1 and TRPV1 channels in the context of nociception. To this end, the proposal is focused on the qualitative and quantitative identification of proteins associated with endogenous TRPA1 and TRPV1 channels during states of acute and inflammatory pain using a proteomics approach. The relevance of identified candidates will be validated in the context of TRPA1 and TRPV1 function, nociceptive signaling and mouse pain behavior. Importantly, domains critically involved in mediating or uncoupling the binding of validated proteins to TRPA1 and TRPV1 channels, respectively, should be identified with the ultimate goal to modulate the respective interaction in vivo while leaving key physiological functions intact. It is anticipated that this project contributes to our understanding of the processes, which give way to chronic pain on the molecular level and provides new molecular targets to specifically relieve chronic pain conditions.

• DFG Programme: Independent Junior Research Groups