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
L1 Retrotransposition: The Missing Link Between Genetics And Environmental Factors In Parkinson's Disease ?
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
The study proposed here focuses on understanding the role of specific mobile DNA sequences in the interaction between environmental and genetic risk factors causing Parkinson’s disease (PD) leading to dementia. The project proposes identification of mobile DNA induced mutations in post-mortem human PD patient brain samples. The significance and mechanisms of mobile DNA induced mutations will be then tested in a PD mouse model.
Interleukin-6 -gp130 Signaling And Actions In The CNS
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
Interleukin-6 (IL-6) is a member of a family of cytokine proteins that may be causative factors in many neurological disorders where they are involved in diverse processes including inflammation, neuronal injury and repair. In this project we will study how IL-6 affects the brain to bring about these outcomes. The results of this work will advance our understanding of how members of this cytokine family function and how they contribute to neurological disease.
Identification And Characterisation Of A Novel Parkinson's Disease Gene
Funder
National Health and Medical Research Council
Funding Amount
$556,313.00
Summary
Parkinson’s disease (PD) is a complex neurological condition affecting 100,000 Australians. The primary clinical features of PD result from the selective loss of a specific type of neuron. These neurons make up less than 1% of the over 50 million neurons within the brain, and it is currently unclear why they are preferentially lost during disease development. We have identified a novel gene that causes early onset parkinsonism. This study will characterise the gene and determine what role it pla ....Parkinson’s disease (PD) is a complex neurological condition affecting 100,000 Australians. The primary clinical features of PD result from the selective loss of a specific type of neuron. These neurons make up less than 1% of the over 50 million neurons within the brain, and it is currently unclear why they are preferentially lost during disease development. We have identified a novel gene that causes early onset parkinsonism. This study will characterise the gene and determine what role it plays in the development of PD.Read moreRead less
Harnessing The Human Postmortem Brain To Elucidate Changes In FK506 Binding Protein (FKBP5) In The Neuropathology Of Severe Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$392,052.00
Summary
The postmortem human brain is a unique source to search for the pathological basis of severe psychiatric disorders including major depression, bipolar disorder and schizophrenia. Postmortem tissues are however being underutilised. This project will apply a selection of powerful biochemical measuring techniques to postmortem human brain tissues to uncover the molecular pathways of severe psychiatric disorders, which is knowledge that can lead to better treatments, preventions and cures.
Mechanisms Of Cortical And Respiratory Degenerations In Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$333,900.00
Summary
This study will be the first to chronicle how and when motor neurons (MNs) in the brain and spinal cord degenerate before, during and after ALS symptoms in 2 different mouse models. The MNs studied control breathing muscles and are a key disease progression and mortality indicator in patients. I expect drastic shape and electrical abnormalities, providing information useful to clinicians about how and when brain and spinal cord MNs degenerate, uncovering new therapeutic targets and time-points.
Controlling The Development And Function Of Hindbrain Commissures In Vertebrate Animals: The Role Of Robo3 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$393,834.00
Summary
Commissural axons connect and coordinate activity between neurons of the left and right sides of the central nervous system. In the forebrain, formation of commissural axons is determined by guidance factors at the midline between the two hemispheres, and abnormalities in guidance can cause developmental malformations. The aims of this project are to elucidate function of the Robo/Slit family of molecules in regulating axon guidance of commissural neurons, particularly in the corpus callosum.
Neurexin And Neuroligin: A Code For Synaptic Development
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
As soon as we are born, we interpret our world through our senses, learn new information and lay down memory. These processes require molecules that connect neurons together. Mutations in genes encoding these molecules result in incorrect wiring of the brain and lead to mental disorders such as autism and schizophrenia. Using simple insect models, our project aims to unravel the fundamental mechanisms of how these molecules function in the brain and how their interaction controls behaviour.
Determining The Role Of Parkin And PACRG In Protein Turnover
Funder
National Health and Medical Research Council
Funding Amount
$555,780.00
Summary
Alterations in the parkin gene are associated with neurodegenerative disorders such as Parkinson's disease (PD). The aim of this proposal is to characterise the function of parkin and the role it plays in disease development. We will determine the role of parkin in the brain and how loss of this function causes specific nerve cells to die. These studies will provide the means to develop novel therapeutic approaches to alleviate or prevent these disorders.
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