Understanding SOCS3 Inhibition Of JAK Activity In Myeloproliferative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
The myeloproliferative disorders are diseases in which abnormal blood cell development leads to a risk of stroke, thrombosis, hemorrhage and leukemia. Remarkably, three of these disorders are caused by an error in a single enzyme that makes it over active. The enzyme, JAK2, controls how cells respond to hormone-like messengers called cytokines. We are investigating a cellular pathway that inhibits this enzyme in order to understand the progression and potential treatment of the disorders.
The Mechanism By Which Apical-basal Polarity Complexes Regulate The Salvador-Warts-Hippo Pathway
Funder
National Health and Medical Research Council
Funding Amount
$540,099.00
Summary
Cancer is a multi-hit process involving the activation of critical signaling pathways leading to increased proliferation, survival and increased invasion-metastasis. We have discovered that a neoplastic tumour suppressor gene, lgl, acts though the Salvador-Warts-Hippo (SWH) tumour suppressor pathway to inhibit cell proliferation and cell survival. Here we use the model organism, Drosophila, and mammalian epithelial cells to determine the mechanism by which Lgl activates the SWH pathway.
The Tumour Suppressor Lgl In The Regulation Of Cell Signaling, Proliferation And Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$534,871.00
Summary
Cancer is a disease that affects 1-3 people at some point in their lifetime. Therefore, understanding what causes cancer is of major importance to medical science. This proposal focuses on a group of tumour suppressors, Scrib-Dlg-Lgl, which act in a common pathway to regulate cell polarity (cell shape) and proliferation. We have shown that Lgl also regulates cell death. This proposal focuses on understanding the mechanism by which Lgl regulates the cell proliferation and death machinery.
Cyclin Dependent Kinases As Drug-Targets To Reduce Renal Cyst Formation And Scarring In Polycystic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$319,446.00
Summary
Polcystic kidney disease (PKD) is one of the most common genetic diseases in humans. The most common type (autosomal dominant-PKD) affects approximately 1:400 to 1:1000 individuals worldwide. Kidney failure is the most debilitating and serious complication of PKD, and it accounts for approximately 10% of the cases of end-stage kidney requiring artificial kidney treatment (dialysis) or transplantation. Over the last decade, major advances have been made in preventing kidney failure due to diabeti ....Polcystic kidney disease (PKD) is one of the most common genetic diseases in humans. The most common type (autosomal dominant-PKD) affects approximately 1:400 to 1:1000 individuals worldwide. Kidney failure is the most debilitating and serious complication of PKD, and it accounts for approximately 10% of the cases of end-stage kidney requiring artificial kidney treatment (dialysis) or transplantation. Over the last decade, major advances have been made in preventing kidney failure due to diabetic kidney disease, but these are ineffective for PKD. As such, currently, there is no treatment to prevent kidney failure due to PKD, and new therapies are needed. PKD is characterised by the development of multiple cysts in the kidney, which enlarge and destroy normal kidney tissue. The growth of the cysts is due to uncontrolled growth (cell division) of the cells of the kidney (epithelial cells), which causes cyst formation. In recent years, gene mutations in proteins called polcysytins are thought to be responsible for the cause of the disease. However, the genetic mutations in PKD are complex (>30 types for autosomal dominant PKD alone), and it is unlikely that gene therapy will be possible with current technology in the near future. A simpler approach is to develop 'drugs' that target the consequences of the mutation. This project will investigate the role of a group proteins, called cyclin-dependent kinases (CDKs) in PKD. CDKs which are enzymes that are critical in promoting cell division. Our preliminary data shows that CDKs are upregulated in PKD. The aim of this project is to establish the importance of CDKs in PKD, and examine the effect of new drugs (CDK inhibitors) in maintaining in preventing cyst growth and kidney scarring in PKD. CDK inhibitors are currently being tested in phase 1 and 2 clinical trials in patients with cancer, and this will facilitate the translation of the findings of this project to humans with PKD.Read moreRead less
Burden Of Disease: Costing An Effective Package Of Care For Mental Disorders
Funder
National Health and Medical Research Council
Funding Amount
$272,735.00
Summary
The Global Burden of Disease project, a WHO-World Bank-Harvard collaboration, presented an unprecedented picture of global health across the developed and developing world, providing much-needed information for planning health services. Health was measured at the population level, and combined the number of life years lost due to death and disablement to give a total amount of life lost per disorder. One surprise of the project was the importance of mental disorders, accounting for 43% of life y ....The Global Burden of Disease project, a WHO-World Bank-Harvard collaboration, presented an unprecedented picture of global health across the developed and developing world, providing much-needed information for planning health services. Health was measured at the population level, and combined the number of life years lost due to death and disablement to give a total amount of life lost per disorder. One surprise of the project was the importance of mental disorders, accounting for 43% of life years lost due to disability in countries like Australia. Service planning to reduce this burden requires knowledge of cost-effective treatments.This project will trial a method used for combining burden and cost-effectiveness data to design an essential package of services to address the treatment shortfall in mental disorders. This research will assist in our understanding of why burden due to mental disorders persists, and the extent to which current treatment knowledge is able to address this burden within existing budgetary constraints. This will be achieved by: 1) detailing the costs and population outcome of current services in Australia for mental disorders, to determine which disorders are currently adequately treated and which disorders require further intervention, 2) calculating the costs and outcome of best practice interventions from clinical practice guidelines, to understand the extent to which current treatment knowledge can reduce burden due to mental disorders, 3) examining the equity consequences of such a package of ideal interventions, with the understanding that the treatment endpoint is not the same for all disorders. This is a secondary analysis, representing a method for translating existing cost and outcome data for individual treatments into their costs and consequences for health planning at the population level.Read moreRead less
Balance disorders are very common, but particularly in those conditions that involve the brain 'balance centres' are often difficult for doctors to diagnose. When diseases are difficult to diagnose, then recommending helpful treatment is particularly challenging. We will use a group of specialized tests to better understand these balance conditions in order to help patients receive accurate diagnoses and therefore, better treatment.
Balance disorders are very common, but particularly in those conditions that involve the brain 'balance centres' are often difficult for doctors to diagnose. When diseases are difficult to diagnose, then recommending helpful treatment is particularly challenging. We will use a group of specialized tests to better understand these balance conditions in order to help patients receive accurate diagnoses and therefore, better treatment.
Molecular Mediators, Epigenetic Modulators And Therapeutic Targets For Cognitive Disorders
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Brain disorders constitute an enormous, and growing, burden. My research investigates how genes and environment combine to cause disorders of cognition, including dementia, schizophrenia and autism. The research will provide new insights into these disorders, at the level of molecules, cells and behaviour. I will explore how genetic and environmental factors interact, with a focus on mental activity, physical exercise and stress, which affect a range of neurological and psychiatric disorders.
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.