I am a cell-development biologist using genetic approaches in the model vertebrate zebrafish to study the regulation of myeloid blood cell development. My laboratory haematology research is in basic science and biology of haemopoiesism but is closely rel
Role Of Neutrophil Proteases In The Mobilisation Of Haemopoietic Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$318,279.00
Summary
Mobilisation is a procedure consisting in inducing the egress of blood forming cells (haemopoietic stem cells) from the bone marrow, where they normally reside, into the blood. The most common agent to induce mobilisation of haemopoietic stem cell is a cytokine called granulocyte - colony stimulating factor (G-CSF). In recent years, the number of transplantations performed with mobilised blood stem cells has exceeded those performed with bone marrow. Elements contributing to this success have be ....Mobilisation is a procedure consisting in inducing the egress of blood forming cells (haemopoietic stem cells) from the bone marrow, where they normally reside, into the blood. The most common agent to induce mobilisation of haemopoietic stem cell is a cytokine called granulocyte - colony stimulating factor (G-CSF). In recent years, the number of transplantations performed with mobilised blood stem cells has exceeded those performed with bone marrow. Elements contributing to this success have been the simplicity of the procedure (daily injections of a mobilising cytokines such as G-CSF), a more rapid recovery following high dose chemotherapy and transplantation, and lower costs. Despite its common use in clinics, the molecular mechanisms responsible for haemopoietic stem mobilisation following injection of cytokines are still unknown. A large body of experimental data demonstrate the critical role of adhesive interactions between blood forming cells and the bone marrow microenvironment These interactions control the lodgement of blood forming cells in the bone marrow, where they normally reside, and their egress into the blood during mobilisation. Experiments from this laboratory have shown that the mobilisation of blood forming cells that follows the administration of G-CSF, may be the consequence of the accumulation in the bone marrow of a class of leukocytes called neutrophils. These neutrophils subsequently release within the bone marrow a set of enzymes that specifically cleave a cell adhesion molecule expressed in the bone marrow, and therefore disrupt the adhesive interactions between the bone marrow and the blood forming cells resulting in their egress in the blood. This proposal aims to demonstrate this hypothesis and to provide tools to predict and improve the levels of mobilisation that can be achieved with healthy donors and cancer patients.Read moreRead less
Role Of Neutrophil Proteases And Their Inhibitors In Haematopoietic Stem Cell Mobilisation
Funder
National Health and Medical Research Council
Funding Amount
$472,750.00
Summary
Mobilisation is the enforced migration of blood forming cells (haemopoietic stem cells) from the bone marrow, where they normally reside, into the blood. The most common agent used to induce mobilisation of haemopoietic stem cells is a cytokine called G-CSF. In recent years, the number of transplantations performed with mobilised blood stem cells has exceeded those performed with bone marrow aspirates. The simplicity of the procedure (daily injections of G-CSF, absence of bone marrow aspiration) ....Mobilisation is the enforced migration of blood forming cells (haemopoietic stem cells) from the bone marrow, where they normally reside, into the blood. The most common agent used to induce mobilisation of haemopoietic stem cells is a cytokine called G-CSF. In recent years, the number of transplantations performed with mobilised blood stem cells has exceeded those performed with bone marrow aspirates. The simplicity of the procedure (daily injections of G-CSF, absence of bone marrow aspiration), better patient recovery and survival, lower costs have all contributed to the success of this procedure. Despite its common use in clinics to rescue cancer patients undergoing high-dose chemotherapy, the reasons why haemopoietic stem cells mobilise are still not fully understood. It is known that haemopoietic stem cells stay in the bone marrow because they express 'adhesive' molecules on their surface. In pioneering work, this laboratory has shown that cytokines such as G-CSF increases the number of neutrophils (a type of white blood cell) in the bone marrow. These neutrophils release enzymes (known as proteases) which cut into pieces the 'adhesive' molecules and other proteins responsible for the retention of blood forming cells within the bone marrow. This project aims to further these investigations to include both the role of proteases and their naturally-occurring inhibitors in the mobilisation of blood forming cells. Particularly, we will investigate how the expression of serpins and TIMPs, two families of protease inhibitors, is regulated in the bone marrow during mobilisation and how these inhibitors control the activity of proteases responsible for the mobilisation of blood forming cells. This knowledge may lead to the design of new treatments that induce more efficient mobilisation and ultimately improve the success of haemopoietic stem cell transplantation.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.