Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
The Intersection Between Hedgehog And Notch Signalling In Medulloblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$620,647.00
Summary
Brain tumours are the second most common malignancy of childhood and the leading cause of cancer related death and disability in children. Medulloblastoma is the most frequent malignant childhood brain tumour, arising in the cerebellum. This application looks at the relationship between two genetic pathways responsible for medulloblastoma which are also drug targets. Understanding this interaction will lead to better treatment options for the disease.
The Genetic Control Of Platelet Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$558,920.00
Summary
Platelets are the tiny cells that circulate in the body and make blood clot. The human body has more than a trillion of them at any one time, and they are replaced every week by the blood producing cells that reside in the bone marrow. Keeping the normal number of platelets steady is incredibly important any significant drop can result in a life-threatening hemorrhage. The clinical name given to a low platelet count is thrombocytopenia, and it is a very common problem. It can be caused by geneti ....Platelets are the tiny cells that circulate in the body and make blood clot. The human body has more than a trillion of them at any one time, and they are replaced every week by the blood producing cells that reside in the bone marrow. Keeping the normal number of platelets steady is incredibly important any significant drop can result in a life-threatening hemorrhage. The clinical name given to a low platelet count is thrombocytopenia, and it is a very common problem. It can be caused by genetic mutations, viral infections, or by cancer treatments like chemotherapy. The only way to raise platelet numbers in a person with thrombocytopenia is a blood transfusion, which carries with it risks and potential side effects. While we understand quite a lot about how the body produces platelets, we don t know anywhere enough to be able to develop new treatments. Our work is focused on the identification of the genes that control the process, beginning with mouse models of thrombocytopenia, genome mapping, gene isolation, and finally, making the links between the newly identified genes and patients with thrombocytopenia. It will give us a much better understanding of how platelets are produced, how things go wrong in human disease, and how new therapies might be developed to treat them.Read moreRead less
Control Of Blood Vessel Development By SOX Transcription Factors
Funder
National Health and Medical Research Council
Funding Amount
$495,750.00
Summary
Cardiovascular disease is Australia s greatest health problem, with an estimated 3 million Australians suffering a spectrum of conditions from hypertension through to heart failure. Improper development of blood vessels in the embryo can compromise survival of the embryo, and predispose patients to vascular disease after birth. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fu ....Cardiovascular disease is Australia s greatest health problem, with an estimated 3 million Australians suffering a spectrum of conditions from hypertension through to heart failure. Improper development of blood vessels in the embryo can compromise survival of the embryo, and predispose patients to vascular disease after birth. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. We discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or properties of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) by drug treatments.Read moreRead less
Role Of The Ets Family Transcription Factor Erg In Stem Cell Function And Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$413,775.00
Summary
The cells responsible for producing blood are called hematopoietic stem cells (HSCs). Our research is focused on the genes that control HSC growth and development. We have discovered that a gene known to cause cancer, Erg, plays a critical role in regulating this process. This Project will tease apart the mechanism by which it does so, provide insights into how Erg can trigger cancer, and help us understand the molecular network of regulators that control blood cell production.
The Effects Of Estrogen-Responsive B Box Protein On Retinoid Sensitivity In Cancer And Its Significance In Development
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
Although effective, many cancer drugs often lead to side effects, especially in children. New therapies are needed that specifically target cancer cells while leaving normal cells unaffected. I am studying a novel protein (EBBP) which I believe has an important role in cancer cell growth. By studying EBBP I aim to be able to increase the effectiveness of the low toxic chemotherapy retinoic acid without increased side effects, as well as understand the functional role of EBBP in cancer cells.