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Séminaire impromptu - Jeffrey HoltFunction, dysfunction and restoration of sensory transduction channels in auditory hair cells.

Abstract :


 Molecular identification of ion channels that mediate sensory  transduction has been a major focus in the field of sensory biology for many years,
yet, the proteins that form sensory transduction channels 
required for hearing and balance have not been definitively identified. 
I will present the latest evidence that supports a role for transmembrane channel-like 1 (TMC1) in hair cell sensory transduction.   
Mutations in TMC1 cause deafness in mice and humans.  In addition to investigating the basic function of TMC1, our lab uses mice that harbor  TMC1 mutations as a model for human genetic deafness.  We find that TMC1 gene therapy can restore sensory transduction and auditory function in 
Tmc1 mutant mice.

Selected publications

Pan B, Askew C, Galvin A, Heman-Ackah S, Asai Y, Indzhykulian AA,  Jodelka FM, Hastings ML, Lentz JJ, Vandenberghe LH, Holt JR, Géléoc GS. Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. Nat Biotechnol. 2017 Mar;35(3):264-272.

Akyuz N, Holt JR. Plug-N-Play: Mechanotransduction Goes Modular.  Neuron. 2016 Mar 16;89(6):1128-30.

Askew C, Rochat C, Pan B, Asai Y, Ahmed H, Child E, Schneider BL, Aebischer P, Holt JR. Tmc gene therapy restores auditory function in deaf mice. Sci Transl Med. 2015 Jul 8;7(295)

Pan B, Géléoc GS, Asai Y, Horwitz GC, Kurima K, Ishikawa K, Kawashima Y, Griffith AJ, Holt JR. TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear.  Neuron. 2013 Aug 7;79(3):504-15.