Characterisation Of The Molecular Mechanisms Of Abeta-induced Proteolysis Of The Neural Cell Adhesion Molecule 2 (NCAM2)
Funder
National Health and Medical Research Council
Funding Amount
$374,666.00
Summary
Neurons in the brain are connected by synaptic contacts. Amyloid beta peptide accumulating in the brain in Alzheimer’s disease destroys synaptic contacts by degrading synaptic cell adhesion molecules which maintain the structure of the contacts. The aim of the project is to characterise the molecular mechanisms of amyloid beta-dependent degradation of synaptic cell adhesion molecules. The project will identify strategies that can be used to inhibit synapse loss in Alzheimer’s disease.
How The Dosage Of A Down Syndrome Candidate Gene Affects Neural Circuitry And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$414,961.00
Summary
In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.
Targeting The Hypoxia Sensing Pathway To Improve Hematopoietic Stem Cell Mobilisation And Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$653,313.00
Summary
Transplantation of patients’ own blood stem cells is used to treat many blood cancers. It increases the chance of cure. However the damage caused by chemotherapies used to combat the cancer can compromise stem cell collection and transplantation. Without transplant, these patients are less likely to survive cancer. This project is to test new drugs that enhance the harvest of blood stem cells for transplantation. These will increase the success rates of transplants and cure in these cancer patie ....Transplantation of patients’ own blood stem cells is used to treat many blood cancers. It increases the chance of cure. However the damage caused by chemotherapies used to combat the cancer can compromise stem cell collection and transplantation. Without transplant, these patients are less likely to survive cancer. This project is to test new drugs that enhance the harvest of blood stem cells for transplantation. These will increase the success rates of transplants and cure in these cancer patients.Read moreRead less
Functional Characterisation Of A New Surface Adhesion Molecule On Human Vascular Progenitor Cells To Combat Cancer
Funder
National Health and Medical Research Council
Funding Amount
$593,794.00
Summary
Collectively, diseases of the blood vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation is a major cause or contributor to many diseases, such as cancer, cardiovascular disease, rheumatoid arthritis, ischemia injury and diabetes. This project aims to understand the underlying mechanisms associated with aberrant angiogenesis such that it may aid in the identification of novel targets for the development of therapeutics.
Failure to correctly regulate cell death leads to a number of diseases, including cancers and auto-immune diseases. Viruses have the ability to hijack the host cell death machinery for their own benefit. Viral infections have been linked to a number of cancers. We aim to target the ability of viruses to hijack the process of cell death to develop new treatments against virus-linked cancers including Burkitt's Lymphoma and Nasopharyngeal Carcinoma.
Investigation Of A New Leukocyte Recruitment Mechanism At Sites Of Vascular Injury
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
Blood clots formed at sites of small vessel injury can cause damage of vital organs by obstructing blood flow and promoting a proinflammatory response by efficiently recruiting and activating leukocytes. The molecular mechanisms responsible for the latter event are poorly defined. We have established a new mouse model, gained novel insights into the leukocyte recruitment by blood clots, and aim to define the precise mechanism for this process in this application.
Investigating The Link Between Oxidative Stress And Biomechanical Integrin Activation In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Diabetes represents a serious healthcare problem globally. A large proportion of deaths associated with diabetes can be attributed to the development of blood clots in the circulation of the heart and brain (heart attack/stroke). The blood clotting mechanism is ‘hyperactive’ in diabetes, although the reason for this is not well defined. In this proposal we will investigate a new mechanism promoting blood clots, and will investigate innovative approaches to reduce this clotting mechanism.
Defining The Role Of Glycosylation In Basement Membrane Failure During Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$824,664.00
Summary
This project aims to utilize mutations within the zebrafish fkrp gene to understand the pathogenic basis of the human diseases associated with mutation of this gene which results in a spectrum of muscular dystrophies. By generating models of alleles that represent the range of phenotypes seen in humans we will have a directly translatable model system to human pathology.
Regulation Of Receptors That Control Platelet Function Under Shear Stress
Funder
National Health and Medical Research Council
Funding Amount
$507,273.00
Summary
Specialized human blood cells that control blood loss and clotting (platelets) are currently difficult to test in the clinical laboratory, meaning patients are at risk of excessive bleeding or serious clot formation during disease or treatment. The aim of this proposal is to use our new reagents and assays to develop more reliable methods for evaluating relative bleeding or clotting risk in individuals.
How Caveolae Condition Tissue Mechanics For An Anti-tumor Niche.
Funder
National Health and Medical Research Council
Funding Amount
$1,091,226.00
Summary
The outcome of cancer is determined not only by the behaviour of the cancer cell, but also by how the normal tissue cells of the body respond to it. This project investigates how tissue cells that surround cancer cells can eliminate early cancers from the body. It develops on newly-discovered mechanisms that allow epithelial tissues to detect and physically expel cancer cells. This mechanism can protect us from cancer, but potentially allow cancer to develop when it fails.