A drosophila model for understanding the basis of meniere’s disease
Too little is known about the complex hearing impairments and vestibular syndromes that develop in adults during their life course; new insights and novel scientific models are required. My project focuses on Meniere’s Disease (MD), a multifactorial impairment of the inner ear characterized by varying grades of (i) adult onset sensorineural hearing loss, (ii) episodic vertigo and (iii) tinnitus. During my PhD, I devised new approaches to decipher the genetic factors contributing to MD by combining whole exome sequencing and bioinformatic analysis. I identified candidate genes for MD and validated the expression of the associated proteins in two functional domains of the human and rodent inner ear: the sensory epithelial sheets of the vestibular system and the auditory Organ of Corti. To understand the functional importance of MD candidate genes, and their interplay with environmental factors, requires an experimentally tractable in vivo model. I here propose to use the hearing and balance system of Drosophila melanogaster as an in vivo model of MD. This will involve devising and employing novel experimental tools, such as novel tests of hearing and vestibular function, genome-wide transcription studies (RNA-Seq) and bioinformatics analysis. The project will provide a better understanding of the heterogeneous landscape of adult-onset inner ear pathologies, which will inform new therapeutic and diagnostic strategies.