Development Of Human Sensory Receptors Of The Inner Ear
Funder
National Health and Medical Research Council
Funding Amount
$418,281.00
Summary
Normal development of our special sense organs is crucial for sight, taste, hearing, and balance. The balance system mediates important postural and eye reflexes that are essential for movement and vision. Abnormal development of the balance system results in dizziness, vertigo, gait deficits, and impaired learning and reading ability in children. This study will investigate how the organs of balance mature and connect with nerve fibres of the inner ear during human development.
Mechanisms Underlying Efferent Feedback In The Vestibular System
Funder
National Health and Medical Research Council
Funding Amount
$491,475.00
Summary
The balance system has a remarkable, but poorly understood capacity for self-repair. An intrinsic feedback mechanism, the Efferent Vestibular System or EVS is thought to play a major role in this self-repair. Surprisingly, we know little about EVS function in animals or humans. We will study the EVS in mice and humans to gain a better understanding of how it works. This information will then drive the design of therapies that improve and restore balance in disease, injury, or ageing.
Gene Therapy For Preventing Progressive Sensorineural Hearing Loss And Restoring Hearing
Funder
National Health and Medical Research Council
Funding Amount
$549,848.00
Summary
This proposal aims to study the clinical feasibility and safety of gene therapy in the guinea pig cochlea for preventing progressive hearing loss and restoring hearing. Two cell survival genes (GDNF and BDNF) will be studied for preserving sensory (hair) cells and hearing nerves, while a gene called Atoh1 will be investigated for its ability to regenerate new hair cells and restore hearing after the onset of progressive hearing loss.
Our vestibular system provides us with the important sense of balance. When it fails we suffer debiltating bouts of vertigo and dizziness. A great deal is known about how balance signals are sent from the inner ear to our brains, but virtually nothing is known about the important signals the brain sends to the inner ear. In this study we will use a new perparation develped in our laboratory to examine how these essential brain signals control the function of our balance organs.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.
Analysis Of Gene Regulation In Disorders Of Sex Development
Funder
National Health and Medical Research Council
Funding Amount
$524,852.00
Summary
Disorders of Sex Development (DSD) are surprisingly common, however the majority of cases still cannot be explained. Our hypothesis is that a significant proportion of DSD is due to disturbed gene regulation. We will use state of the art methods to analyse the regulation of DSD genes. Our research will improve our knowledge of the regulation of genes that affect DSD and provide a diagnosis for DSD patients for whom the underlying cause is unknown. This in turn will improve clinical management.
Muscle Fusion Defects May Be A Common Cause Of Human Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$391,419.00
Summary
While muscle fusion is a crucial step of muscle formation, it is surprising that human muscle diseases were never associated with muscle fusion defects. We have recently undertaken a genome-wide functional screen using a mouse muscle cell line. We identified 21 genes that were previously associated with muscle dystrophies in human. The aim of this project is to examine the role of those genes during muscle fusion in vivo, using the chick embryo, mouse mutants and lines from patients as models.
Birth defects can have devastating consequences for individuals and their families, and improving our ability to diagnose and screen for these disorders has implications for treatment and reproductive options. We are using the mouse as a model to discover genes important in a new class of birth defects caused by dysfunction of a hair-like cellular projection known as the cilium.
Stress-induced Disease Risk For Pregnant Mothers Born Small
Funder
National Health and Medical Research Council
Funding Amount
$613,124.00
Summary
This proposal addresses the likelihood that mothers born small and exposed to stress during pregnancy will develop adverse physiological adaptations to pregnancy, slowing placental and fetal growth, programming intergenerational disease and compromising maternal health later in life. The outcomes from our human and rat studies will enable development of diagnostic tests to identify pregnancies at greater risk and lead to therapies to reduce adverse intergenerational and long-term health effects.