NEURAL MODULATION OF HEARING LOSSES INDUCED BY LOUD SOUND
Funder
National Health and Medical Research Council
Funding Amount
$290,500.00
Summary
Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with ....Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with a view to optimising such mechanisms. I propose to build on seminal Australian work to examine how one such system, nerves from the brain to the inner ear (the site of most damage from loud sounds), modulates hearing losses caused by loud sounds. Early studies indicated these nerves could protect from damage induced by short-lasting loud sound and this has led to international interest in functional applications of such protection to reduce hearing damage suffered by humans. However, my recent work indicates the nerves exert complex protective and exacerbative effects to loud sounds similar to common trauma or occurring under conditions similar to common trauma. They even exacerbate hearing losses due to loud sound, especially when there is an imbalance in hearing sensitivity in the two ears (bilateral) similar to what is common in humans. These findings make it critical that functional application be delayed until the full range of effects exerted by the nerves is understood. I propose to elucidate the novel complex effects of these nerves to loud sound. Specific aims are: (1) To understand effects of these pathways to loud sounds like those encountered by humans, (2) To investigate how chronic imbalanced bilateral hearing sensitivity, like that common in humans, alters effects of the nerves and when they change from being protective to exacerbative, (3) To adduce how an atraumatic sound affects hearing losses due to later loud sound and the role played by these nerves.Read moreRead less
The immune system employs a variety of strategies to combat parasites including viruses. One of them is cytolytic lymphocytes, cells that can recognize and destroy virus-infected target cells. These cells use, besides other molecules, enzymes called granzymes to kill target cells by inducing suicide in them. We intend to investigate if those granzymes can protect cytolytic lymphocytes themselves from being infected by viruses and turned into viral factories. We are going to use a model of a natu ....The immune system employs a variety of strategies to combat parasites including viruses. One of them is cytolytic lymphocytes, cells that can recognize and destroy virus-infected target cells. These cells use, besides other molecules, enzymes called granzymes to kill target cells by inducing suicide in them. We intend to investigate if those granzymes can protect cytolytic lymphocytes themselves from being infected by viruses and turned into viral factories. We are going to use a model of a natural infection, ectromelia, mouse pox. Mouse pox is fatal in resistant strains of mice if the genes for the two dominant granzymes are deleted. This indicates that granzymes are essential for fighting this viral disease. We will explore in which cells of the immune system granzymes are expressed and whether virus entry into a cell can actually trigger their expression. Furthermore, we will investigate how the granzymes inhibit virus infection within the infected cell to determine whether the mechanisms involved resemble those used by cytolytic lymphocytes in killing of target cells (i.e. degradation of DNA and mitochondrial damage), or whether they represent entirely new facets of granzyme function. Finally, using viruses from a number of different families, we will establish whether these functions of granzymes also contribute to protection from other viral infections. An understanding of the role of these granzymes in the innate immune response, i.e. before antigen specific T cell and antibody responses are fully activated, is of great significance as it may allow us to manipulate this particular anti-viral response and thus enhance survival and reduce morbidity in viral infections.Read moreRead less
Improving Music Appreciation For People With Prosthetic Hearing Devices By Enhancing Auditory Stream Segregation
Funder
National Health and Medical Research Council
Funding Amount
$266,560.00
Summary
Music perception is one of the most often-cited problems for people with hearing aids or cochlear implants. Part of the problem is related to the reduced ability to hear different instruments or melodic lines separately. This ability is based on perceptual differences between auditory streams. Psychophysics experiments will be performed to understand the effect of different acoustic parameters on auditory streaming. An innovative approach to restore music appreciation will be tested on people wi ....Music perception is one of the most often-cited problems for people with hearing aids or cochlear implants. Part of the problem is related to the reduced ability to hear different instruments or melodic lines separately. This ability is based on perceptual differences between auditory streams. Psychophysics experiments will be performed to understand the effect of different acoustic parameters on auditory streaming. An innovative approach to restore music appreciation will be tested on people with impaired hearing.Read moreRead less
The Role Of Mitochondrial DNA In Age-related Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$260,475.00
Summary
Hearing loss is an extremely common and under-studied age-related disability, affecting 39% of Australians aged 50 years or older. Both genetic and environmental factors may contribute to the development of age-related hearing loss. Human genetic material (DNA) resides in two places in body cells; the nucleus and in organelles called mitochondria. This is due to the fact that mitochondria were derived from bacteria that were engulfed by the cell back in primordial life. Although this genetic mat ....Hearing loss is an extremely common and under-studied age-related disability, affecting 39% of Australians aged 50 years or older. Both genetic and environmental factors may contribute to the development of age-related hearing loss. Human genetic material (DNA) resides in two places in body cells; the nucleus and in organelles called mitochondria. This is due to the fact that mitochondria were derived from bacteria that were engulfed by the cell back in primordial life. Although this genetic material is different to nuclear DNA, it has an essential role in helping to provide energy for the cell. Genetic mutations in the DNA residing in the mitochondria have been associated with a number of conditions, usually affecting tissues that require large amounts of energy, such as the brain, muscle, heart, retina and the cochlea of the ear. The commonest clinical manifestation of mitochondrial disease is thought to be hearing loss. This project investigates the role that abnormal mitochondrial DNA plays in the development of hearing impairment by studying subjects from a representative Australian community who participated in a large population study of hearing loss. We will assess whether different sectors of mitochondrial DNA predispose particular individuals to the development of hearing loss or accelerate its onset. The Blue Mountains Hearing Study is able to take into account other factors known to be associated with hearing loss (industrial noise exposure, diabetes, smoking).Read moreRead less
The discoveries made to date and the proposed studies point to an intrinsic role for vitamin D compounds in skin in providing protection from sun damage. As a result of sun exposure, increased concentrations of vitamin D compounds in skin will be generated and this is likely to provide protection against further UV damage, in much the same way as increased pigmentation and increased thickness of the outer layer of skin. Furthermore, the studies are designed to test whether vitamin D compounds wh ....The discoveries made to date and the proposed studies point to an intrinsic role for vitamin D compounds in skin in providing protection from sun damage. As a result of sun exposure, increased concentrations of vitamin D compounds in skin will be generated and this is likely to provide protection against further UV damage, in much the same way as increased pigmentation and increased thickness of the outer layer of skin. Furthermore, the studies are designed to test whether vitamin D compounds which have minimal effects on serum calcium, could nevertheless be used topically in association with a sunscreen or moisturizer to add to sun protection. As Australia has the highest skin cancer rates in the world, this would be of significant health and economic value.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.