Transregional Collaborative Research Centre 152

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About the CRC

TRiPs to Homeostasis:

Maintenance of Body Homeostasis by Transient Receptor Potential Channel Modules

Transient receptor potential (TRP) channels represent a diverse protein family with salient roles as versatile cellular sensors and effectors. TRP proteins control an exceptionally broad spectrum of homeostatic physiological functions, illustrated by more than 20 hereditary human diseases caused by mutations in 11 Trp genes. Most TRP channel-related human disorders impinge on development, metabolism and other homeostatic functions. However, a detailed understanding of the underlying pathophysiology is missing. There is accumulating evidence to link TRP channels to even more human diseases beyond TRP channelopathies, and accordingly, TRP proteins have been identified as appealing therapeutic targets. A major impediment to the dissection of TRP channel function in vivo is the lack of reliable and precise pharmacological tools. Therefore, this consortium focuses on the physiology and pathophysiology of TRP ion channels, in particular their role for the maintenance of body homeostasis. The researchers set out to develop novel molecular tools and techniques to investigate TRP channel function in vivo. Notably, the CRC will benefit from investigations of human patients with TRP channel mutations and from the largest available collection of mouse models harbouring genetically engineered trp genes. Thus, special emphasis will be placed on the characterization of endogenously expressed ion channels, for instance by investigating primary cells isolated from genetically modified mouse models or inducible pluripotent stem cells derived from human patients. Three central questions will be addressed:

(1) What are the building blocks of native TRP channels in defined tissues/cells and how do TRP channels interact functionally in defined cellular compartments?

2) What is the physiological role of TRP channels in vivo and what is the precise mechanism of their activation in native environments?

(3) What are the detailed pathomechanisms underlying human diseases caused by dysfunctional TRP proteins?

This research will help overcome a merely genetic classification of TRP channels by means of physiologically relevant functional criteria, thus leading to a functional re-definition of what is presently called the “TRP channel family”. Such fundamental insight will furthermore open up new avenues for specific, tailored treatment options for patients suffering from diseases inflicted by dysfunctional TRP proteins.
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