Project Title: Physiological basis of hearing loss in Tasmanian devil mutant mice
Supervisor: Dr Walter Marcotti
Co-Supervisor: Dr Stuart Johnson
Project Description:
Mammalian hearing depends on mechanosensory hair cells within the inner ear that convert sound into electrical signals. Relatively little is known about the molecular mechanisms that regulate the functional development of hair cells. Therefore, one of the major challenges in hearing research is to understand the genetic and physiological basis of how the auditory system develops. This is an extremely ordered process involving specific functional and morphological changes that, in most cases, are regulated by genetic programmes. One of the challenges in modern medicine is to implement new and effective therapeutic strategies to treat deafness by targeting specific genes that play a crucial role in the disease.
In this project we propose to investigate the physiological properties of a mouse model (Tasmanian devil: Erven et al 2002) for a form of nonsyndromic deafness found in humans (DFNB25: Odeh et al 2010). DFNB25 is caused by a mutation in Grxcr1 (Odeh et al 2010), a gene encoding for a protein expressed in the stereocilia and implicated in their morphological growth. Therefore, we aim to identify the functional/physiological consequences of this mutation in order to determine the cause of deafness in humans, making the proposed research cutting edge. Most of the work will be conducted using electrophysiological and molecular biology techniques (i.e. Kuhn et al 2011).
References:
- Erven A et al. (2002)
A novel stereocilia defect in sensory hair cells of the deaf mouse mutant Tasmanian devil.
Eur J Neurosci 16: 1433-1441. - Kuhn S et al. (2011)
miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells.
Proc Natl Acad Sci USA 108:2355-60. - Odeh H et al. (2010)
Mutations in Grxcr1 are the basis for inner ear dysfunction in the pirouette mouse.
Am J Hum Genet 86: 148-160.
Contact Details:
Dr Walter Marcotti & Dr Stuart Johnson
http://www.shef.ac.uk/bms/research/marcotti
Email: