Strabismus is the pathological misalignment of the eyes associated with loss of binocular vision and is one of the most common human ophthalmological disorders. Patients with comitant strabismus have full eye movements, whereas patients with incomitant strabismus have limited eye movements, which causes the angle of strabismus to vary with gaze direction. This project aims to define genetic contributors to comitant congenital strabismus.
Understanding The Causes Of Childhood Congenital Anomalies Of The Kidney And Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$609,748.00
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified ....Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified genes.Read moreRead less
Identification And Characterisation Of Novel Genes For Congenital Cataract
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Au ....Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Australia over the past 5 years to determine the causative genes. A large number of families have been involved in the study and solid progress has been made in identifying mutations in cataract genes and understanding what effect these may have on the patient's prognosis. We have recently identified a new gene in a large Australian family with a syndrome of cataract, mental retardation and teeth problems. This syndrome, known as Nance-Horan syndrome was originally described in Australia 30 years ago and we have worked with the original family to find the exact gene responsible. We already know that this gene causes the same syndrome in other families and in this project we will examine whether it can cause cataract without the other features or mental retardation without cataract. We will perform a series of experiments to learn what this gene does and how it causes the disease. We have also selected 3 other very interesting families with congenital cataracts for further study as we either know already or strongly suspect that they will enable us to identify further new genes for cataract, and in one case mental retardation. Our work in other diseases indicates that understanding the genes in severe young onset cases can give valuable clues to the causes of age-related forms and may in the future enable new ways to prevent and treat the commonest cause of worldwide blindness.Read moreRead less
The Role Of The Mammalian Grainyhead-like Gene Family In Neural Tube Closure
Funder
National Health and Medical Research Council
Funding Amount
$569,541.00
Summary
Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Anencephaly is not compatible with life and affected babies die at birth. In contrast children with spina bifida survive, but suffer from limb paralysis, bowel and bladder dysfunction, learning diff ....Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Anencephaly is not compatible with life and affected babies die at birth. In contrast children with spina bifida survive, but suffer from limb paralysis, bowel and bladder dysfunction, learning difficulties and psycho-social disturbances. Our laboratories have identified a family of genes essential for the colsure of the neural tube in mammals. The aim of this proposal is to understand the mechanisms of action with a view to developing new therapeutics that mey be used preventatively in these conditions. We also hope that these studies may facilitate the development of a genetic test to screen couples at risk.Read moreRead less
Ocular Motility In Autism And Asperger S Disorder: Dissociation Of Motor Deficits.
Funder
National Health and Medical Research Council
Funding Amount
$131,235.00
Summary
We will use ocular motor technology to investigate motor dysfunction in autism and Asperger's disorder, to advance our understanding of the neurobiological bases of these disorders. This will help clarify whether neural networks are differentially disrupted in these disorders, as our previous clinical research suggests. This dissociation and the subsequent development of an ocular motor clincal screen may improve diagnosis, and potentially treatment, of these devastating conditions.
Emerging Severe Mental Illness In Young People: Clinical Staging, Neurobiology, Prediction & Intervention From Vulnerabi
Funder
National Health and Medical Research Council
Funding Amount
$6,229,421.00
Summary
Mental disorders, such as psychotic and severe mood disorders, are the largest cause of disability in Australia. However, there is still little known about illness onset, relapse and progression. We have developed a clinical staging model with transition points from symptomfree to subthreshold status, to threshold disorder to chronic disability. We will investigate neurobiological and psychosocial factors which increase the risk of progression through these stages and use this model as a basis f ....Mental disorders, such as psychotic and severe mood disorders, are the largest cause of disability in Australia. However, there is still little known about illness onset, relapse and progression. We have developed a clinical staging model with transition points from symptomfree to subthreshold status, to threshold disorder to chronic disability. We will investigate neurobiological and psychosocial factors which increase the risk of progression through these stages and use this model as a basis for examining the effectiveness of interventions, for example to prevent, delay or ameliorate onset and relapse, and promote vocational recovery. Thus major clinical and public health benefits and an understanding of factors that contribute to the onset and progression of illness will result.Read moreRead less
NeuroSleep: The Centre For Translational Sleep And Circadian Neurobiology
Funder
National Health and Medical Research Council
Funding Amount
$2,659,061.00
Summary
NeuroSleep, the Centre for Translational Sleep and Circadian Neurobiology, will foster innovative clinical research and translation to develop national capacity in understanding how sleep disorders and dysfunction of the body clock impact on health. The Centre will focus its activities on the two-way relationship between disrupted sleep and body clock systems and brain disorders. Our goal is to improve brain performance, workplace safety and health outcomes in patients with sleep and circadian d ....NeuroSleep, the Centre for Translational Sleep and Circadian Neurobiology, will foster innovative clinical research and translation to develop national capacity in understanding how sleep disorders and dysfunction of the body clock impact on health. The Centre will focus its activities on the two-way relationship between disrupted sleep and body clock systems and brain disorders. Our goal is to improve brain performance, workplace safety and health outcomes in patients with sleep and circadian dysfunction and in the general community.Read moreRead less
Motor Functioning In Autism And Asperger's Disorder: Furthering Current Neurobehavioural And Clinical Definitions
Funder
National Health and Medical Research Council
Funding Amount
$354,932.00
Summary
While it is well known that autism and Asperger's disorder are associated with social, communicative, and behavioural symptoms, it is less well known that affected individuals also have considerable movement and coordination difficulties. For example, these children often have problems with hand writing, walking, hopping, skipping, catching, and running. These skills are very important for success at school; for example, if children are unable to participate in school sports they often feel isol ....While it is well known that autism and Asperger's disorder are associated with social, communicative, and behavioural symptoms, it is less well known that affected individuals also have considerable movement and coordination difficulties. For example, these children often have problems with hand writing, walking, hopping, skipping, catching, and running. These skills are very important for success at school; for example, if children are unable to participate in school sports they often feel isolated and rejected from the peer group. Also, hand writing problems have a significant impact on children's academic performance. Our previous research has suggested that there may be particular patterns of motor problems that characterise individuals with autism and Asperger's disorder. Our proposed research aims to use the kinds of 3D motion analysis technology used in the movie industry to capture exactly how people affected by these conditions move and respond to the environment. This study will enable us to highlight particular parts of the brain-motor circuitry that are affected by these disorders and will also enable us to more clearly distinguish how autism is different from Asperger's disorder. Ultimately, it is hoped that our motor investigations will lead to improved assessment and interventions for these disorders.Read moreRead less
Neourobiology Of Human Epilepsy: Genes, Cellular Mechanisms,network And Whole Brain
Funder
National Health and Medical Research Council
Funding Amount
$17,652,824.00
Summary
The team is comprised of neurologists, molecular geneticists, physiologists and brain imaging specialists and leads the world in the discovery of the genetic causes of epilepsy. They will continue to identify genes underlying epilepsy and study how genetic variations result in development of seizures. Advanced brain imaging will be used to understand the effects of genetic variation on brain structure and function. This study may lead to new diagnostic methods and treatments for epilepsy.
Defining The Epigenetic Origins Of Maternally Inherited Disease.
Funder
National Health and Medical Research Council
Funding Amount
$731,162.00
Summary
Epigenetic (non genetic) changes to the DNA in sperm and eggs can alter outcomes in children. Despite the potential for drugs and diet to mediate some of these inherited effects, the processes involved are very poorly understood. By determining the mechanisms that regulate epigenetic inheritance, this project will improve our understanding of how epigenetic mechanisms acting in the parent, can mediate inherited disease and life-long health outcomes in our children.