Role of Acsl4 and lipid metabolism in high frequency hearing loss
Research division: Wolfson Centre for Age-Related Diseases
First supervisor: Professor Karen P Steel
PhD Mentor: Professor Patrick Doherty
Sponsor: Action on Hearing Loss (RNID)
Duration: 3 years
Study mode: Full time
Stipend: Starts at £17,000
Start date: 1 October 2013
Application closing date: 31 January 2013
Hearing impairment is a heterogeneous disorder with a wide range of causes, including a strong genetic component. The majority of people affected by deafness suffer progressive hearing loss, which is profoundly isolating and has a major impact on the quality of life. In progressive hearing loss, it is often the high frequencies that are lost first. However, we know very little about the molecular basis of progressive hearing loss. This project will use one of the first mouse mutants found with high frequency hearing impairment, as a model for human deafness. This mutant is of particular interest because it involves a gene (Acsl4) that has a role in lipid metabolism and there are small molecules available that can moderate this function. Understanding the pathological processes underlying hearing loss in this mutant will lead to a more general understanding of the role of lipid metabolism in auditory function and may suggest drug treatments. The mutation of Acsl4 in the mouse can be regarded as an access point for understanding the role of lipids in deafness whatever the initial trigger may be, so the benefits will not be confined to people with ACSL4 mutations. The aims of the project are:
- To determine the molecular, cellular and electrophysiological basis of high frequency hearing impairment in a newly-discovered mouse mutant carrying a targeted mutation of Acsl4.
- To ask if the Acsl4 mutant can tell us more about the general role of lipid metabolism in deafness by comparison with other genes important for lipid processing and by building a network of the interactions of Acsl4 protein with other molecules involved in lipid physiology to suggest other candidate genes that may underlie hearing loss and offer alternative targets for drug development.
- To manipulate lipid metabolism using small molecules known to moderate pathways involving Acsl4 to ask if this can affect the hearing impairment.
Applications are welcome from graduates with a first- or upper-second class degree in a relevant life sciences subject such as neuroscience, molecular genetics, physiology, or other general biological subjects.
How to apply
Please send a full CV, covering letter and details of at least two academic referees to firstname.lastname@example.org by the deadline, 31 January 2013.
Please direct enquiries about this studentship project to Professor Karen Steel.