Obiettivo
The hair bundles of the sensory cells play a central role in the processing of sounds by the cochlea. Various performances of auditory perception depend upon what biophysical and physiological environment the operating hair bundle can provide to its mechanoelectrical transduction (MET) channels. The project aims at building a more integrated view of the way the hair bundle works. Reaching this goal, requires to understand the interdependence of its functional building blocks and their dynamic interplay.
To this purpose, the objectives of the work are :
1. To assemble components of the basal MET machinery
The work aims at
a) identifying the molecular players of the basal MET machinery, most of which are still unknown
b) deciphering their functional interactions,
c) developing a simple and efficient tool to validate candidate components of the MET machinery.
2. To elucidate the coupling between MET and stereocilia F-actin polymerisation
The work aims at
a) characterising this coupling, both in development and in steady-state condition,
b) deciphering the role of tip-link tension and Ca+2 influx through the MET channel,
c) developing a coarse-grained mathematical model of this coupling, experimentally testable.
3. To understand the interplay between MET, waveform distortions, and masking
The work aims at
a) deciphering biochemical characteristics of the top connectors,
b) explaining why large waveform distortions vanish in the absence of top connectors,
c) determining how the operating outer hair cell (OHC) hair bundle contributes to the masking effect in auditory perception.
The hair bundle is a highly vulnerable structure, actually the main target structure of noise-induced hearing loss and hereditary deafness forms. As such, advances in the understanding of the mechanisms underlying its functioning will pave the way for the development of therapeutic approaches.
Campo scientifico
Invito a presentare proposte
ERC-2011-ADG_20110310
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Meccanismo di finanziamento
ERC-AG - ERC Advanced GrantIstituzione ospitante
75724 Paris
Francia