Hearing is the sense of communication. It is a necessary condition to the learning of any vocal exchange within a species, including oral language in humans.
Our lab has historically mostly focused on human hereditary sensory disorders affecting olfaction (Kallmann’s syndrome) or vision (Usher syndrome), with a particular interest in hearing. The main aim of our team is to elucidate the cellular and molecular physiology of hearing. Our work which continually bridges the gap between basic science and medicine also targets at unravelling the pathogenesis of hearing disorders (and some visual defects) with a view of developing innovative therapeutic interventions.
The cochlea, the mammalian auditory sensory organ, is an electroacoustic organ with amazing properties. The human cochlea detects acoustic energy at levels less than ten times the energy of thermal noise and acoustic intensity covering 12 orders of magnitude. It responds to a spectrum of frequencies extending up to 8-9 octaves (from 20 Hz to 20 kHz) and can discriminate differences in frequency as small as 1/1000. The cochlea carries out three major functions: it performs frequency analysis, it amplifies sounds, and it operates acoustic-electric transduction, a microphonic function performed within microseconds. As a result of its non-linear functioning, the cochlea also generates sound distortions and suppressive masking. The basic principles of cochlea functioning were worked out by physicists since the 19th century. In contrast, at the beginning of the 1990s, their underlying molecular mechanisms were still entirely unknown. The very small number of cells within the cochlea has impeded their characterisation. Indeed, there are only 3000 genuine sensory cells per cochlea (the inner hair cells), an extremely small number compared to the 108 sensory cells per retina, the photoreceptor cells. To circumvent these problems, our team has developed a genetic approach of the cochlear cellular and molecular mechanisms. We opted for a neurogenetic approach of hearing in humans, which has the additional advantage of providing clinically relevant information in parallel. We mapped the first two genes underlying childhood autosomal recessive deafness (DFNB1 and DFNB2) and identified more than 20 causative genes of hearing impairment. We have developed an interdisciplinary approach involving the study of mouse models of various forms of human deafness as well as cell- and temporal-specific conditional knock-out mice. This has enabled us to unravel the pathogenic processes of a large spectrum of deafness forms as well as some of the mechanisms involved in sound processing in the peripheral auditory system. Of note, the lab has a major interest in Usher syndrome (which includes both hearing and visual impairment). We aim to explore both the basic science and the clinical aspects of this disorder, with a special focus on the structure-function relationship of the complexes formed by the Usher proteins in the photoreceptors and auditory hair cells, in particular in the auditory mechanotransduction (MET) machinery. We are developing in gene therapy approach of the retinal defect of this syndrome in collaboration with the “Vision Institute” in Paris..