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Understanding The Role Of RAS Mutations In Thyroid Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$463,854.00
Summary
My fellowship will examine the association of RAS mutations in thyroid cancer. RAS proteins are the most mutated in cancer and I will investigate how they work in thyroid cancer. RAS mutated thyroid cancer is more likely to cause death. This grant will be based in the pioneering lab of Prof Fagin at Memorial Sloan Kettering Cancer Center and the Garvan Institute of Medical Research. It is hoped by understanding these mutations, new treatments for thyroid cancer can be developed.
Biomarkers For The Treatment And Prognosis Of Sight-threatening Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$598,305.00
Summary
Diabetic retinopathy (DR) is a highly specific vascular complication of both type 1 and type 2 diabetes, with prevalence strongly related to the duration of diabetes. Clinic biomarkers of DR have become the basis for preventive medicine. In this project, we aim to evaluate possible biomarkers in both Chinese and Australian diabetic populations at different stages of DR. We will also investigate pathological mechanisms and novel drugs to treat DR in animal models.
Characterization Of Novel Regulators Of Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature fu ....Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature functional cells. We have identified six molecules which interact with Lyn in red blood cells. We have shown that amolecule called HS1 is important for epo function in individual red blood cells and now we plan to investigate its functions in whole animals, including mice that lack the HS1 gene. We have also shown that a molecule called Trip1 is important for red blood cell development. Interestingly, this molecule also interacts with the thyroid hormone receptor and can influence the effects of epo and thyroid hormone on red blood cell development. The interplay between these two hormones will be looked at in more detail both at the cell and whole animal levels in normal mice and those lacking the thyroid hormone receptor gene. The third Lyn binding molecule we isolated is a novel gene-we have named it ankyrin repeat protein in line with the molecules it is related to. This gene is expressed in red blood cells and we aim to investigate what role it plays in the development of these cells. The fourth gene is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Its role in red blood cell structure will also be investigated. Finally, the last two molecule we have identified are both novel and are unrelated to any other known proteins. As above, the effects of these two molecules on red blood cell development will be investigated.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
Novel Epidemiological Methods To Infer The Causal Effects Of Risk Factors On Neuropsychiatric And Cardiovascular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$182,003.00
Summary
Epidemiological studies, which associate risk factors and disease, are central in informing public health policy. Because causality is difficult to ascertain from these associations, public health interventions based on these findings are at some risk of failure. We propose to develop, extend and apply an innovative epidemiological approach, Mendelian randomization (MR) to resolve the causal relationship between risk factors and neuropsychiatric and cardiovascular disorders.
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.
Delineating The Relationship Between Iron And Peroxisomal Disorders: The Role Of The Peroxisomal Enzyme GNPAT In Iron-Overload Disorders
Funder
National Health and Medical Research Council
Funding Amount
$700,767.00
Summary
Hereditary haemochromatosis is one of the most common genetic disorders in humans, affecting 1 in 200 Australians. We have identified a change in a peroxisomal gene which may affect iron levels in humans. The prevalence of this gene change in Australian haemochromatosis patients will be examined followed by a systematic analysis of how this protein controls iron levels in the body. Our goal is to identify and diagnose genetic changes which influence iron loading in haemochromatosis patients.