In the normal process of hearing, the brain actively selects sounds of interest from competing background sounds. This normal auditory function is indispensible for children and adults to cope in non-optimal listening environments, however the mechanisms by which such performance is achieved are poorly understood. This project will investigate the nerve circuits that enable this to occur and will also investigate how these circuits malfunction in various types of partial deafness. The results wi ....In the normal process of hearing, the brain actively selects sounds of interest from competing background sounds. This normal auditory function is indispensible for children and adults to cope in non-optimal listening environments, however the mechanisms by which such performance is achieved are poorly understood. This project will investigate the nerve circuits that enable this to occur and will also investigate how these circuits malfunction in various types of partial deafness. The results will improve our understanding of how we detect sounds and the impact of hearing pathologies on this process.Read moreRead less
Nerve pathways exist that carry information from the highest parts of the brain to the peripheral hearing organ, the inner ear. These descending control pathways have the potential to affect the hearing process in a number of ways; protecting from loud sounds, improving the detection of signals in noisy backgrounds, selecting stimuli of interest and regulating a variety of aspects of inner ear function. Abnormal function of these pathways can affect hearing sensitivity and may be important in ph ....Nerve pathways exist that carry information from the highest parts of the brain to the peripheral hearing organ, the inner ear. These descending control pathways have the potential to affect the hearing process in a number of ways; protecting from loud sounds, improving the detection of signals in noisy backgrounds, selecting stimuli of interest and regulating a variety of aspects of inner ear function. Abnormal function of these pathways can affect hearing sensitivity and may be important in phenomena such as tinnitus and other disorders of hearing. This project will investigate the subtle effects that selective activation of these pathways has on inner ear function and will attempt to unravel the different influences that subcomponents of the pathways have on the different aspects of hearing.Read moreRead less
Normal hearing relies on the generation and transmission of electrical signals in the hearing organ, the inner ear. These electrical signals are generated by the action of specialized molecular ion channels in the cellular membranes of the inner ear and this research aims to charcterize these ion channels and detail their role in the hearing process. The results will impact on our understanding of human hearing disorders such as tinnitus, auditory neuropathy and disturbances of loudness sensatio ....Normal hearing relies on the generation and transmission of electrical signals in the hearing organ, the inner ear. These electrical signals are generated by the action of specialized molecular ion channels in the cellular membranes of the inner ear and this research aims to charcterize these ion channels and detail their role in the hearing process. The results will impact on our understanding of human hearing disorders such as tinnitus, auditory neuropathy and disturbances of loudness sensation.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
Cell-based Neurotrophin Delivery With Cochlear Implantation For Long-term Rescue Of Auditory Neurones Following Deafness
Funder
National Health and Medical Research Council
Funding Amount
$437,212.00
Summary
This project aims to develop safe and effective techniques for long-term delivery of drugs to the ear by genetically modifying cells so they release the theraputic agents over extended periods of time, and then to use encapsulation techniques to safely deliver these cells to the inner ear in combination with a cochlear implant.
The Role Of Proteases In Deafness; Generation Of A Knockout Mouse For Tmprss3 As A Model Of Autosomal Recessive Deafness
Funder
National Health and Medical Research Council
Funding Amount
$70,880.00
Summary
Age-related hearing loss is the most common type of human hearing impairment, affecting approximately half the population by the age of 80. The interaction of predisposing genetic factors with environmental factors is responsible for most age-related hearing loss. Genes underlying genetically inherited hearing impairment also affect susceptibility to age-related hearing loss. Approximately 1-1000 children are born deaf and ~50% of these cases have a genetic cause. Autosomal recessively-inherited ....Age-related hearing loss is the most common type of human hearing impairment, affecting approximately half the population by the age of 80. The interaction of predisposing genetic factors with environmental factors is responsible for most age-related hearing loss. Genes underlying genetically inherited hearing impairment also affect susceptibility to age-related hearing loss. Approximately 1-1000 children are born deaf and ~50% of these cases have a genetic cause. Autosomal recessively-inherited defects are responsible for most cases of genetic deafness (70%) and patients have no other medical problems, indicating that only the inner ear is affected. Genes previously identified for genetic forms of deafness can be broadly classified as either ion channels (e.g. connexins) or structural proteins (e.g. myosins and collagens). We recently identified a novel gene, a transmembrane serine protease, TMPRSS3, which is mutated both in familial and sporadic cases of deafness. Different classes of mutations may cause either deafness from birth or childhood onset deafness. Thus, reduced expression or abnormal function of TMPRSS3 may be involved in age-related hearing loss. This discovery was the first description of a protease involved in hearing loss and the first gene family involved in congenital deafness for which a ready hypothesis for involvement in age-related hearing loss can be made. We will generate and characterize a mouse model to investigate the role of TMPRSS3 in inner ear function and development. We will also isolate and characterize additional members of the transmembrane protease gene family to investigate further the role of proteases in both genetic and age-related hearing loss. This may lead to a greater understanding of the function of the auditory system and, eventually, to new therapeutic protocols.Read moreRead less
Population Outcomes And Cost-effectiveness Of Universal Newborn Hearing Vs Risk Factor Screening At Age 5 Years.
Funder
National Health and Medical Research Council
Funding Amount
$540,423.00
Summary
Universal newborn hearing screening (UNHS) is being widely implemented because it is thought to greatly improve outcomes for children with congenital deafness. However, it is also very costly. Between 2003-5, all New South Wales babies were offered UNHS, while Victorian babies were offered a risk-factor screening and referral program. This two-year 'natural experiment' paves the way for a unique population effectiveness and cost-effectiveness study of UNHS as the children reach 5 years of age.
Most adults will have already sustained damage to the tiny connections between hearing cells and nerve cells; a missing link in their auditory pathway. There is no way to repair the damage and our hearing will worsen over time. We now have compelling evidence that a growth factor therapy to the inner ear restores the connections. We will deliver world-first data to justify and set the parameters for a clinical trial for a therapy to treat hearing loss for the first time.