Surdités, acouphènes et thérapies

Our goal is to unravel the mechanisms of deafness and tinnitus to envision therapies. This requires i) the analysis of animals mutant that recapitulate human auditory deficits, ii) to decipher the sound encoding process and iii) to develop new diagnostic tools for auditory disorders screening.

1. The logic of sound coding

1.1 Molecular determinants of hair cell exocytosis

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Inner hair cells transduce sound stimulation into neurotransmitter release onto auditory nerve fiber. However, the synaptic release from hair cells does not recapitulate the secretion from the central nervous system. To identify the molecular synaptic machinery, we are using multi-disciplinary approaches from molecular biology to cellular and system level physiology.

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1.2 Wiring and activity of auditory nerve fibers

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Auditory nerve fibers convey sound-information from sensory cells to brainstem through neural spike trains. Dysfunction in the sound encoding process leads to deafness and tinnitus. Here, we combine morphological, electrophysiological investigations with computational modeling to examine the mechanism of sound encoding in the auditory nerve fibers.

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2. Sensory loss and Repair

2.1 ER pathies

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Endoplasmic reticulum (ER) is the key organelle for the synthesis of secreted and transmembrane proteins. Perturbations in ER lead to an accumulation of unfolded or misfolded proteins. As a consequence, the unfolded protein response (UPR) adapts ER capacity to demand. Under prolonged stress, UPR switches from a cell survival promoter to an apoptosis trigger. ER stress thus emerges as a potential cause of deafness.

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2.2 Age-related hearing loss

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Age-related hearing loss or presbycusis is a major health problem. Cumulative effects of aging on hearing are exacerbated by genetic and environmental factors such as noise or drug exposure. Here, we are using multi-disciplinary approaches to decipher the mechanisms of presbycusis and to develop therapies against hearing loss at elderly.

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3. From Diagnostic tools to Clinical trial