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An introduction to Bernd Nilius's Festschrift

This special symposium issue of The Journal of Physiology contains four review articles from selected speakers at ‘TRP 2010: TRP channels, from structure to disease.’ This two-day symposium was organized on the special occasion of the 65th birthday of Bernd Nilius, founder of the Laboratory of Ion Channel Research at the University of Leuven, former Reviewing editor of The Journal of Physiology, and one of the leading figures in the field of TRP channel research. The 145 participants met at the medieval Grand Beguinage of Leuven (Belgium) for two days filled with exciting accounts of today's TRP channel research in all its facets, vivid and open scientific discussions and amusing anecdotes about Bernd Nilius's career and personality. 
 
TRP channels form a large superfamily of cation channels (including 28 mammalian members) related to the Drosophila trp (transient receptor potential) gene. For many years, TRP channels have been considered as newcomers in the ion channel world. Indeed, our knowledge about the structure, gating mechanisms and (patho)physiological role of TRP channels has lagged behind that of other ‘classical’ families of cation channels, such as for example the voltage-gated Na+, K+ or Ca2+ channels or the ligand-gated cys-loop receptors. However, participants to the symposium will most likely agree that the TRP field is now coming of age. The 15 invited speakers illustrated many of the significant recent advances in the field, ranging from atomic detail of the structure of TRP channels and their ligands, to important clinical insight into their role in acquired and inherited human diseases. 
 
Molecular insight in TRP channel function was provided by Rachel Gaudet (Boston), who gave an overview of existing crystal structures of intracellular domains of TRPV channels and their role in channel regulation (Gaudet, 2008), and Giovanni Appendino (Novara), who presented a chemist's view on natural products and their derivatives as potent TRP channel ligands. Nevertheless, the participants agreed that achieving crystal structure of entire TRP channels – arguably the final step to adulthood – should be high on the priority/wish list. 
 
That the TRP channels should no longer be considered as the youngsters of the ion channel family was especially evident from the lecture of Ardem Patapoutian (San Diego), who presented a completely novel class of transmembrane proteins, the Piezos, that form cation channels activated by mechanical stimuli. In the light of these findings, the proposed role of some TRP channels as direct mechanosensors may need to be revised. In his lecture, Lutz Birnbaumer (Research Triangle Park) presented data supporting the existence of channel complexes consisting of TRP channels and members of another novel family of cation channels, the Orais, an intriguing but certainly controversial view (see e.g. DeHaven et al. 2009). The complexity of the cellular regulation and function of TRP channels was further highlighted in the lecture by Reinhold Penner (Hawaii), who reported about the dual role of TRPM2 as plasma membrane and lysosomal Ca2+-permeable channel (see Sumoza-Toledo & Penner, 2011; this issue). 
 
During the last decade important advances have been made concerning the role of TRP channels in different organ systems, especially by using genetically modified and/or pharmacologically treated model animals (from fruitfly to mouse). In particular, the key role of TRP channels as sensors for temperature and osmolality and mediators of pain in the peripheral nervous system is well established, and recent new insights were presented in the lectures of Stuart Bevan (London), Gary Lewin (Berlin) and Craig Montell (Baltimore). The much less understood role of TRP channels in the central nervous system was touched on by David Clapham (Boston), who illustrated the role of TRPC5 in the amygdala and in fear-related behaviour. Rudi Vennekens (Leuven) discussed some recent evidence about the role of TRP channels in the cardiovascular system, as novel modulators of vascular tone and cardiac function (see Vennekens, 2011; this issue). Finally, Thomas Gudermann (Munich) and Rene Bindels (Nijmegen) summarized current insight into the role of TRP channels as epithelial Ca2+ and Mg2+ channels (see Dimke et al. 2011; this issue). 
 
An important goal of current TRP channel research is to provide novel insight into human disease, which may ultimately lead to new diagnostic and therapeutic options (Nilius & Owsianik, 2010). As discussed by Sven-Eric Jordt (New Haven), TRPA1, which acts as a detector of environmental chemicals by the respiratory system, could be an important target for the treatment of Asthma. Dan Cohn (Los Angeles) gave a clinical view on the variety of TRPV4 gene mutations that cause bone deformation diseases, thereby illustrating the high medical relevance of basic TRP channel research. 
 
The final lecture of the symposium was by the celebrant himself. Bernd Nilius spoke about the ‘irritating nature’ of TRP channels, referring not only to the role of these channels as sensors of irritating chemicals, but also to their mind-boggling and often poorly understood biophysical properties (see Nilius et al. 2011; this issue). At the end of his inspiring lecture, Bernd Nilius performed a hilarious live experiment – a modern version of E. H. Weber's silber Thaler illusion (Weber, 1846) – to directly ‘prove’ the mechanosensitivity of TRPA1. A great finale to two days of exciting science.