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
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 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
Early Detection Of Hearing Damage In Children Receiving Anticancer Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$197,500.00
Summary
Children surviving cancer are often left with a severe permanent hearing loss. However, very little progress has been made to minimize hearing damage in this special population. Early detection of hearing damage is not possible using traditional assessment tools. The present research seeks to investigate the use of innovative testing techniques to identify hearing damage in the early stages of the disease with high accuracy. If successful, the research will alter standard audiometric practice in ....Children surviving cancer are often left with a severe permanent hearing loss. However, very little progress has been made to minimize hearing damage in this special population. Early detection of hearing damage is not possible using traditional assessment tools. The present research seeks to investigate the use of innovative testing techniques to identify hearing damage in the early stages of the disease with high accuracy. If successful, the research will alter standard audiometric practice in hospital clinics around Australia, hence improving the standard of hearing health care for this group. The early diagnosis of hearing impairment will not only provide a chance for doctors to balance the therapeutic effects of anticancer drugs against the danger of a permanent hearing loss, but also enable allied health professionals and educational specialist to provide timely management strategies. The determination of the rate and extent of hearing dysfunction progression in children receiving chemotherapy, as proposed in this research, enables the ototoxic effects of existing drugs to be compared. With this approach, the ototoxic side effects of new drugs can also be evaluated. In summary, the proposed study will improve the quality and efficiency of audiological service delivery to young children undergoing chemotherapy in Australia and overseas.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.
Enabling Safe Leisure Activity Participation For Young Hearing Aid Wearers
Funder
National Health and Medical Research Council
Funding Amount
$47,537.00
Summary
There is community concern that exposure to loud sound during everyday activities, (such as, using iPods,MP3 players), may be damaging young peopleÍs hearing, and researchers around the world are investigating this issue. There is little information about how exposure to loud sound affects young people who already have permanent hearing loss, so the National Acoustic Laboratories (NAL) is conducting a study (iHEAR2) to find out whether loud sound exposure is affecting young hearing aid wearers.
Both hearing and balance are vulnerable during ear surgery, and the loss of either carries a heavy personal, social and economic cost. We will develop new ways of protecting the ear during surgery, though the local delivery of medication to the inner ear. The protocol will be developed in the laboratory and tested in a clinical trial. This research will stand to benefit all people undergoing major operation on their ear, and especially cochlear implant candidates with residual hearing.
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