CINV Postdoctoral Fellowship Program 2014
Research Area: Physiological mechanisms of deafness associated to connexin 26 (Cx26) mutations
Laboratory: Inter-cellular communication
Senior researcher: Agustín Martínez
B.Sc. Biology. University of Havana, Cuba (2000)
M.Sc. Animal Physiology, University of Havana, Cuba (2006)
Ph.D. Health Science, University of Medical Science, Havana, Cuba (2013)
E-mail: pavel.prado at cinv.cl
Fax: (56)-(32)-250 8047
Address: Centro Interdisciplinario de Neurociencia de Valparaíso.
Facultad de Ciencias, Universidad de Valparaíso.
Gran Bretaña 1111. Playa Ancha. Valparaíso. Chile.
In the cochlea, gap junction (GJ)-based intercellular communication networks localize among supporting cells of the Organ of Corti (OC) and also among cells of connective tissue. Those networks are indispensable to maintain the high potassium concentration and the endocochlear potential in the scala media, two critical aspect for the mechanical transduction of hair cells. Connexine 26 (Cx26) and connexine 30 (Cx30) are the predominant cochlear Cx and they generally co-assemble to form hybrid GJ. Mutations in Gjb2 (gen codifying for Cx26) are linked to about a half of the inherited prelingual deafness and all the autosomal dominantly inherited sensorineural hearing loss (SNHL).
We aim to describe the physiological mechanisms of deafness associated to connexine 26 (Cx26) mutations, answering one of the key questions related with the genetic SNHL. Our hypothesis is that mutations in Cx26 induce SHNL by disrupting the purinergic signaling pathway during the development of the cochlea. We are interested in analysing the GJ-based inter-cellular communication and the function of hemichannels in the developing cochlea in both intact animals and organotipic cultures of the OC. In that sense, we are focused on the development of a model of genetic deafness by the cochlear expression of mutated Cx26 in mice mediated by lentivirus infection, a novel and efficient approach of gene delivery vector. Finally, using electrophysiological, immunohistochemical and image aproaches, we aim to characterize the biophysical properties of the corresponding hybrid channels in exogenous expression systems.
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