Inner Ear Protein Function Studied Using RNA Interference
Funder
National Health and Medical Research Council
Funding Amount
$365,230.00
Summary
The proper functioning of all cells tissues and organs depends on specific proteins that are manufactured by readout from the genome. The inner ear is no exception to this general principle and hence the normal hearing process depends critically on the proper functioning of key proteins. However, because of inherent limitations in the methods used to study their function in living tissues, the precise role of many inner ear proteins in the complex hearing process is not known or is at best poorl ....The proper functioning of all cells tissues and organs depends on specific proteins that are manufactured by readout from the genome. The inner ear is no exception to this general principle and hence the normal hearing process depends critically on the proper functioning of key proteins. However, because of inherent limitations in the methods used to study their function in living tissues, the precise role of many inner ear proteins in the complex hearing process is not known or is at best poorly understood. In this project we will use a recently developed technique called RNA interference, to reduce the amounts of specific targeted proteins in the inner ear of experimental animals. We will then study the effects on the inner ear's ability to detect sounds. The technique differs from other genome-manipulating methods because it can be applied to a single intact organ in the mature animal. The results of this project will illuminate the role of specific inner ear proteins in the process of sound detection. The project will also demonstrate the feasibility of using the RNA interference technique to modify function in the adult inner ear, thus paving the way for future therapies for inherited hearing disorders.Read moreRead less
A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second grou ....A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second group of plastic phenomena depend upon minute changes in the connections between neurons and these are invoked in the first few days following an injury (synaptic plasticity; changes in the pattern and strength of the connections between neurons). Aside from being model systems, there are also parallels of this plasticity with clinical situations such as losses in hearing and sight, and of the adaptations made by the brain in response to prosthetics (e.g. bionic ear) and resorative surgery but the degree of relevance for these situations is unclear. An intriguing aspect of the experiments on auditory and visual systems is that neurons with inputs from both ears, or both eyes, undergo the plastic changes when the relevant sense organ on only one side is damaged but the other is intact. In fact, on the basis of the limited available evidence, it appears that the changes are independent of there being a normal input from the other side. This is difficult to explain in terms of the modern understanding neuronal plasticity at a cellular level. It is thus proposed to study both auditory and visual models of this brain plasticity with stimuli which are systematically varied to extract the extent of bilateral interaction in the induced plasticity. This will enable prediction of how these plasticity mechanisms will be involved in adaptations made to prosthetics and surgical corrections.Read moreRead less
Hearing Protection Conferred By P2X2 Receptor Signaling In The Cochlea
Funder
National Health and Medical Research Council
Funding Amount
$580,019.00
Summary
Hearing loss from noise damage and ageing is the principal sensory disability in our society. This project will determine the contribution of the P2X2 receptor to protection from noise-induced hearing loss. We have found that P2X2 knockout mice have minimal temporary threshold shift. We will investigate the physiological basis for this and determine why this mouse model has greater hearing loss with intense sound and faster age-related hearing loss compared with wildtype controls.