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SENSATIONAL TETHERS SIGNED

Tethers for sensory mechanotransduction: from molecules to perception

Total Cost €

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EC-Contrib. €

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Partnership

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 SENSATIONAL TETHERS project word cloud

Explore the words cloud of the SENSATIONAL TETHERS project. It provides you a very rough idea of what is the project "SENSATIONAL TETHERS" about.

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Project "SENSATIONAL TETHERS" data sheet

The following table provides information about the project.

Coordinator
MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) 

Organization address
address: ROBERT ROSSLE STRASSE 10
city: BERLIN
postcode: 13125
website: www.mdc-berlin.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-07-01   to  2023-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) DE (BERLIN) coordinator 2˙500˙000.00

Map

 Project objective

Touch sensation is built upon the ability of sensory neurons to detect and transduce nanometer scale mechanical displacements. The underlying process has been termed mechanotransduction: the high sensitivity and speed of which is enabled by direct gating (opening) of ion channels by mechanical force. Force detection is functionally compartmentalized and only takes place at the peripheral endings of sensory neurons in vivo. Two molecules are known to be genetically necessary for touch in many sensory neurons, the force gated ion channel PIEZO2 and its modulator STOML3. However, mechanotransduction complexes in all touch receptors absolutely require tethering to the extracellular matrix for function. Tethering is dependent on large extracellular proteins that are sensitive to site-specific proteases. Here we will not only identify the nature of these tethers, but will develop technology to acutely and reversibly abolish tethers and other mechanotransducer components. We will use genome engineering to tag tether and mechanotranduction components in order to visualize and manipulate these proteins at their in vivo sites of action. By engineering de novo cleavage sites for site-specific proteases we will render tethers and ion channels newly sensitive to normally ineffective proteases in the skin. We will engineer mutations into candidate ion channels that dramatically alter biophysical properties to physiologcally “mark” function in vivo. Finally we will develop new behavioural paradigms in mice that allow us to measure touch perception from the forepaw. Psychometric curves for different vibrotactile tasks can then be precisely compared between humans and mice. Furthermore, the impact of acute and reversible manipulation of mechanotransduction on touch perception can be measured. Understanding how molecules assemble to function in a mechanotransduction complex in the skin will open up avenues to develop therapeutic strategies to modulate touch.

 Publications

year authors and title journal last update
List of publications.
2020 Ricardo Paricio-Montesinos, Frederick Schwaller, Annapoorani Udhayachandran, Florian Rau, Jan Walcher, Roberta Evangelista, Joris Vriens, Thomas Voets, James F.A. Poulet, Gary Richard Lewin
The sensory coding of warm perception
published pages: , ISSN: 0896-6273, DOI:
Neuron 2020-03-23

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