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Enzymes that generate or degrade peptides serve important roles - alterations in their activity can impact on a diverse range of physiological processes in healthy and diseased states. Angiotensin is a peptide that plays a critical role in regulating blood pressure and fluid balance - drugs that block the activity of its processing enzymes forms an important class of medication used to treat hypertension and heart disease. My research interest is in discovering novel roles for these enzymes.
Retinal Microvascular Signs In Acute Stroke: Prognostic Significance And Relevance To Underlying Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$375,425.00
Summary
This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that asses ....This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that assess size of the small retinal arteries compared to veins (the arteriole-to-venule ratio) and will document other abnormalities, such as microaneurysms, haemorrhages, tortuosity and focal and generalised vessel narrowing and wall opacity. In normal populations these signs are associated with hypertension, inflammation and endothelial dysfunction and predict future stroke. These signs, and their significance have not been systematically studied in acute stroke. This may offer a window into the brain for important subgroups of stroke such as lacunar stroke. It is increasingly hard (and remains technically very difficult) to study the cause of lacunar stroke, affecting 10,000 Australians each year, as lacunar stroke has a lower fatality rate (and thus few opportunities for post mortem studies) but a high disability rate. Lacunar stroke is known to be due to small vessel disease but the exact nature of this disease is unknown. Echocardiography (to identify heart and major blood vessel abnormalities) and carotid duplex scanning (to identify critical stenosis of the major blood supply to the brain) are commonly normal in this type of stroke, and brain scanning with computerised tomography (CT) or magnetic resonance (MR) merely shows the outcome of the small vessel disease. The eye develops as part of the brain and thus retinal vascular abnormalities could add important knowledge to our understanding of stroke and add clinically useful data in the assessment of patients with stroke.Read moreRead less
Mapping, recovery and remediation of arm coordination deficits after stroke. Coordination of arm movement is a significant problem after a stroke. This innovative project will underpin new treatments by focusing on what type of stroke causes difficulty in coordinating arm movement, describing the coordination difficulties in detail and investigating mechanisms of recovery and treatment.
Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
Defining The Changes In Cell Biology Caused By PRESENILIN Truncations Associated With Different Diseases
Funder
National Health and Medical Research Council
Funding Amount
$622,886.00
Summary
Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be requir ....Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be required for the development of treatments.Read moreRead less
Muscling in on the brain. This project investigates an enzyme that 'matures' neurotransmitters in the brain that regulate food intake, energy expenditure and blood pressure by the brain; these neurotransmitters arise from the same precursor molecule. This project will show the physiological relevance of this enzyme in obesity.
Longitudinal Transcriptome Profiles For People With Dementia
Funder
National Health and Medical Research Council
Funding Amount
$475,913.00
Summary
Over the past decade, less than half a percent of drugs trialled for Alzheimer Disease were found to be effective. This highlights the need for new drug targets. This Fellowship aims to study how genes express themselves over time, among people with very high risk of dementia (genetic form of Alzheimer Disease and Huntington Disease). By looking at gene expression in nerve tissue in the nose, fluid around the brain, and blood, I hope to better understand the disease mechanisms causing dementia.
SELECTIVE VULNERABILITY IN ALZHEIMER’S DISEASE AND RELATED DISORDERS: MECHANISM OF TAU PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$1,072,324.00
Summary
Alzheimer’s disease and related dementias affect 230,000 people in Australia, with numbers expected to grow to 730,000 by 2050. The direct costs for health and residential care alone exceed $6.6 billion per annum. By identifying genes that protect degenerating neurons in the Alzheimer brain, a deeper understanding of the underlying processes will be gained and therapeutic targets will be defined that will assist in developing a therapy for a yet uncurable disease.