Identification of TRPV1- and TRPM8-independent novel molecular sensors for high and low temperature.

• Applicant: Dr. Hans Jürgen Solinski
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250903377

The mammalian thermosensory system provides important information about environmental temperature. It is integral to the individual's survival given that every physiological process requires a proper thermal homeostasis. Malfunctions of this system either lead to spontaneous pain at physiological innocuous temperature (thermal hyperalgesia) or to a high propensity of tissue damage after noxious stimulation due to decreased avoiding behavior.Molecular sensors for temperature are expressed in thermoceptive primary sensory neurons and tuned to respond to distinct thermal thresholds. Notably, the transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1) senses in vivo extreme high temperature (> 50 °C), especially in inflammation, while there is little data to suggest that TRPV1 is additionally required for behavioral orientation to warm and hot stimuli in non-injury conditions. Similarly, the TRP melastatin subfamily member 8 (TRPM8) has been established as major molecular cool sensor (10 - 30 °C) but does not respond to extreme low temperature in the noxious range. Additional candidate molecular temperature sensors, including TRPs and other ion channels, have been suggested. However, perception of the complete physiologically relevant temperature range is not covered by today's molecular temperature sensors.Therefore, this project aims to identify and characterize novel temperature-sensitive receptor proteins. The strategy I plan to employ makes use of recent data derived from cellular ablation of distinct subpopulations of primary sensory neurons. This work suggests that additional unidentified warm/hot temperature sensors are present in TRPV1 expressing neurons, while TRPM8 marks a cellular population that harbors novel molecular sensors for extreme low temperature. I will use a transcriptomic screening approach in conjunction with iterative in vitro and in vivo characterization in order to elucidate the molecular basis for temperature sensation in these cellular subpopulations. These novel insights will increase the understanding of the somatosensory system and help to initiate new routes to treat somatosensory malfunctions that are often accompanied by pain in humans.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Mark A. Hoon, Ph.D.