The overall incidence of primary brain tumours in the Western world is 10 per 100,000 people. Unlike many other tumours, these occur in patients of all ages and comprise the second most common tumour type among children and young adults. Most brain tumours remain incurable. We are using our expertise in the field of neural stem cell research to characterise tumour cells responsible for resistance to treatment, with the final goal of identifying new targets for therapeutic intervention.
Roles Of Brain-derived Neurotrophic Factor In The Regulation Of Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$299,625.00
Summary
Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to ....Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to analyse physiological roles of BDNF in the brains stem and spinal cord in the regulation of nerve activity and blood pressure. The successful execution of the project will significantly enhance our understanding of how blood pressure is controlled by BDNF and nerve activity. The knowledge from this study will form basis for designing new drugs to control high blood pressure.Read moreRead less
Headache Prophylaxis By Cortico-brainstem Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$616,437.00
Summary
In this project we hope to discover the cause of migraine headache. Many triggers lead to migraine, but we do not know how. We believe the triggers produce a defect in pain control by the brainstem, which normally keeps sensation from the head below the pain threshold. In migraine, trigger factors acting high in the brain open a pain control gate lower in the brain, producing a migraine headache. If we can prove this, we can develop therapies that will prevent migraine before it starts.
The Role Of The Transcriptional Co-activator, Qkf, In Adult Neural Stem Cell Self-renewal And Multi-potency.
Funder
National Health and Medical Research Council
Funding Amount
$403,709.00
Summary
In recent years there has been considerable interest in stem cells because they have the potential to provide new therapeutic approaches to disease. Indeed, haematopoietic stem cells are already used in treatments for leukaemia. Many organs in adult humans contain stem cells, including the brain. In order to develop safe, and effective, stem cell-based treatments for human diseases it is necessary to determine how proliferation and differentiation are regulated in adult stem cells.
PURINERGIC TRANSMISSION AND CENTRAL AUTONOMIC REGULATION
Funder
National Health and Medical Research Council
Funding Amount
$157,848.00
Summary
The brain regulates bodily functions in a complex manner. One such example is the regulation of blood pressure and heart rate. This is achieved by an interconnected network of brain nuclei that sense information from the major blood vessels and integrate appropriate responses to maintain the status quo. Chemicals called neurotransmitters convey the nervous messages, and one such example is purines, which include ATP and adenosine. Both ATP and adenosine can act in a number of brain regions to mo ....The brain regulates bodily functions in a complex manner. One such example is the regulation of blood pressure and heart rate. This is achieved by an interconnected network of brain nuclei that sense information from the major blood vessels and integrate appropriate responses to maintain the status quo. Chemicals called neurotransmitters convey the nervous messages, and one such example is purines, which include ATP and adenosine. Both ATP and adenosine can act in a number of brain regions to modulate blood pressure and heart rate. This project is designed to characterise the mechanism by which purines act within specific brain nuclei to regulate the cardiovascular system. Considering the large economic burden on the healthcare system caused by cardiovascular disease, this research is vital to increase our understanding of how diseases such as hypertension may be caused, and therefore provide improved therapeutic strategies.Read moreRead less
Investigation Of Delta3 Function And Notch Signalling During Cell Fate Specification In Mouse And Human
Funder
National Health and Medical Research Council
Funding Amount
$221,717.00
Summary
This project seeks to understand how cells within the developing embryo are produced and how they are given a specific identity. These processes often require the cell to make a decision about what type of cell it will become. We are using the Delta3 gene, which is present in humans and in the mouse, as a tool for our investigations. Delta3 is expressed at the surface of the cell and Notch (its receptor) is present on the surface of neighbouring cells. Delta3 on one cell will bind to Notch on th ....This project seeks to understand how cells within the developing embryo are produced and how they are given a specific identity. These processes often require the cell to make a decision about what type of cell it will become. We are using the Delta3 gene, which is present in humans and in the mouse, as a tool for our investigations. Delta3 is expressed at the surface of the cell and Notch (its receptor) is present on the surface of neighbouring cells. Delta3 on one cell will bind to Notch on the neighbouring cell and activates Notch. When Notch is activated in a cell it pushes the cell to make its decision. This project aims to determine what exactly is the function of Delta3 in mammals and how at the level of the individual cell this protein exerts its effects. We have generated a mouse in which the Delta3 gene is no longer active and have observed that embryos do not develop normally. We will explore these defects (which affect the skeleton and the brain) in detail in order to define their origins. We will also use these abnormal mice to identify genes, which require the function of Delta3 for their normal activity. It is not only important to define the function of Delta3 in mammals but also to determine this protein functions. We wish to know how exactly Delta3 interacts with Notch. That is, which part of the Delta3 protein binds to which part of the Notch protein. We can address this by modifying the Delta3 protein in small (but revealing ways) and see if it can still bind the Notch receptor in a cell culture assay. Our studies have relevance to humans because recently it has been shown that Delta and Notch are associated with a human syndrome (spondylocostal dysostosis) in which individuals suffer from abnormal skeletons.Read moreRead less
Understanding how the brain grows and is organised is one of the great challenges of science. This project seeks to identify key regulators of neural progenitors as these are the building blocks from which all brains cells are derived. This knowledge may also identify new avenues through which to manipulate neural progenitor function. This has implications not only for normal brain development but also potential therapies for neural disorders and disease.