Université de Strasbourg

Thomas Grutter


Laboratory of Design and Application of Bioactive Molecules (CAMB), University of Strasbourg and CNRS

Thomas Grutter, USIAS Fellow 2019

Thomas Grutter studied chemistry and biology at the University of Strasbourg (Magisterium chemistry and biology). He obtained his doctorate in bio-organic chemistry while working in the laboratory of Professor Maurice Goeldner at the University Louis Pasteur Strasbourg. During his postdoctoral training he oriented his research towards the study of structure and function of channel receptors in neuronal communication in Professor Jean-Pierre Changeux’s laboratory at the Institut Pasteur in Paris. He joined the CNRS in 2003 and in 2007 obtained his accreditation to lead research projects. In the same year he set up his own research team at the Faculty of Pharmacy in Illkirch (Strasbourg) and was promoted to CNRS director of research in 2012 in the CAMB laboratory. His research team focused on biophysical and molecular aspects of P2X channel receptors through ATP by combining several approaches, such as the recording of unique channels by patch-clamp electrophysiology coupled with molecular sensors. He also developed, in collaboration with Alexandre Specht, innovatory (photo-)chemical tools applied to channel receptors.

Thomas Grutter received the La Recherche Prize in 2014 and is also deputy director of CAMB. His publications notably include his pioneer work on the development of the first P2X receptor activated by light (PNAS 2013), as well as on biophysical aspects of the opening mechanism and ionic permeation (PNAS 2011; EMBO J. 2012, eLife 2016; PNAS 2017). His work established the basis for the current USIAS project, the objective of which is to explore structural-function relationships of Piezo channels, an emerging family of ionic channels activated mechanically by novel nano-optical clamps.

Project - Molecular engineering of Piezo channels with innovative opto-nano-tweezers

01/11/2019 - 28/02/2022

Piezo proteins are mechanosensitive ionic channels that are found in numerous physiological functions such as the perception of touch or the regulation of the cellular volume of red blood cells. They form trimeric transmembrane pores where the openings are controlled by the mechanical deformation of the plasmic membrane. Recent studies reveal that these channels have a molecular architecture similar to those of other trimeric channels, including P2X receptors. The results suggest that these channels, which do not derive from a common ancestral gene, have converged over the course of time towards a similar trimeric structure. However, it is not known whether these channels share a common mechanism action. The project includes finding the answer to this question by studying the molecular mechanisms that control the activation of Piezo channels.

It is proposed to use nano-optical tweezers, recently developed on P2X receptors, as investigative tools combined with patch-clamp electrophysiology. These nano-optical tweezers have a central photo-switch sensitive to light, the geometrical change of which is controlled by luminous irradiation to precise wavelengths. These tweezers, which are thus correctly and irreversibly positioned in the ionic pore, allow the molecular movements of Piezo channels to be controlled, and in this way the conformational changes linked to the passage of ions can be measured. In comparing these molecular movements to those already obtained on the P2X receptors, it will then be possible to know if these channels share the same activation mechanism. This project will be completed by experimental studies whose aim would be to identify autonomous functional modules that can regulate the parental channel activity. The data obtained should shed new light on the molecular mechanism to activate Piezo channels, the discovery of which only dates back to 2010. In the course of time, this project could contribute to the development of new drugs.

Post-doc biography - Francisco Peralta

Laboratory of Design and Application of Bioactive Molecules (CAMB), University of Strasbourg & CNRS

Francisco Peralta

Dr. Francisco Peralta was born in Chile in 1987. He obtained his BSc degree in Biochemistry in 2014 at the Pontificia Universidad Católica de Valparaiso in Chile, working with Dr. Esteban Aliaga on protein expression and phosphorylation in rodent models of autism spectrum disorder using biochemical and molecular biology techniques.

During his PhD dissertation while in the laboratory of Dr. Juan Pablo Huidobro-Toro, Dr. Peralta worked on the allosteric modulation of P2X receptors through divalent cations, using a combination of electrophysiology, molecular biology, molecular modeling, and molecular dynamics, where he dissected the molecular determinants of the positive modulation of the receptor. Dr. Peralta obtained his PhD in Neuroscience at the University of Santiago in Chile in 2018.  In addition, and in collaboration with Dr. Alexis Aspée (Department of environmental sciences), he worked on the modulation of P2X2 receptors through polyphenols.

After finishing his PhD, he worked as a short-term post-doc in Dr. Elias Leiva-Salcedo’s laboratory investigating the role of cholinergic signaling in the excitability of the medial prefrontal cortex and its underlying channels. Francisco has now joined Dr. Thomas Grutter’s group as a post-doc to study Piezo channels.


  • Article in PNAS: Jiang, R., Lemoine, D., Martz, A., Taly, A., Gonin, S., Prado de Carvalho, L., Specht, A. & Grutter, T. (2011) Agonist trapped in ATP-binding sites of the P2X2 receptor. Proc. Natl. Acad. Sci. USA 108, 9066-9071.

  • Article in Chemical Reviews: Lemoine, D., Jiang, R., Taly, A., Chateigneau, T., Specht, A. & Grutter, T. (2012) New insights into the structure of ligand-gated ion channels and their implications in therapeutic interventions. Chem. Rev. 112, 6285-6318

  • Article in EMBO J.: Jiang, R., Taly, A., Lemoine, D., Martz, A., Cunrath, O. & Grutter, T. (2012) Tightening of the ATP-binding sites induces the opening of P2X receptor channels. EMBO J. 31, 2134-2143.

  • Article in PNAS: Lemoine, D., Habermacher, C., Martz, A., Méry, P.F., Bouquier, N., Diverchy, F., Taly, A., Rassendren, F., Specht, A. & Grutter, T. (2013) Optical control of an ion channel gate. Proc. Natl. Acad. Sci. USA 110, 20813-20818.

  • Article in eLife: Habermacher, C., Martz, A., Calimet, N., Lemoine, D., Peverini, L., Specht, A., Cecchini, M., & Grutter, T. (2016) Photo-switchable tweezers illuminate pore-opening motions of an ATP-gated P2X ion channel. eLife 5, e11050

  • Article in PNAS: Harkart, M., Peverini, L., Cerdan, A.H., Dunning, K., Beudez, J., Martz, A., Calimet, N., Specht, A., Cecchini, M., Chataigneau, T., & Grutter, T. (2017) On the permeation of large organic cations through the pore of ATP-gated P2X receptors. Proc. Natl. Acad. Sci. USA 114, E3786-E3795.

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