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
Australian Centre For Vertebrate Mutation Detection (ACVMD)
Funder
National Health and Medical Research Council
Funding Amount
$1,611,794.00
Summary
Over the last 20 years, generation and analysis of genetically modified animals has proven to be an important step in the transition from in vitro studies of gene function to in vivo studies and eventually clinical research. The remarkable parallels between the human, mouse and zebrafish genomes means that there are now many examples of mutations that cause or modify disease in humans, and which lead to similar phenotypes when present in mice and zebrafish. Until recently, the prime method of in ....Over the last 20 years, generation and analysis of genetically modified animals has proven to be an important step in the transition from in vitro studies of gene function to in vivo studies and eventually clinical research. The remarkable parallels between the human, mouse and zebrafish genomes means that there are now many examples of mutations that cause or modify disease in humans, and which lead to similar phenotypes when present in mice and zebrafish. Until recently, the prime method of introducing mutations into specific genes of interest in the mouse (although still unavailable in the fish) was via homologous recombination, and the principal classes of mutations induced were large deletions or insertions. This type of mutation rarely occurs in humans. Rather, point mutations and single-nucleotide polymorphisms are the prevalent form of genetic variation. An alternative approach to the development of mouse models with the more relevant point mutations is TILLING (Targeting Induced Local Lesions IN Genomes). The goal of this Enabling Grant is to make TILLING technology accessible to the Australian research community and in doing so promote movement of research from the in vitro setting into animal models of disease.Read moreRead less
Antitumour Efficacy Of TRAIL: An Immunotherapeutic Approach For The Treatment Of Skeletal Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$459,034.00
Summary
The most serious clinical problem with patients with solid tumours is metastasis to bone, which leads to complications that can cause erosion of the patient's quality of life, and eventually death. TRAIL is a new cancer therapeutic that selectively kills cancer cells while sparing normal cells. The use of TRAIL agonistic antibodies that do not bind OPG and have increased serum half life offers an exciting approach for the treatment of skeletal malignancies that is non toxic and safe.
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.
Precision Epigenetics: Targeting The Epigenome To Treat Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,940,576.00
Summary
Epigenetic marks are changes made to the DNA that allow genes to be switched off in some cells and switched on in others. These marks are critical to normal development and often go wrong in disease. We aim to find genes that add epigenetic marks to the DNA and understand how they co-operate at the molecular level to switch genes off. Our focus is on one such gene, SMCHD1. We are developing new drugs against SMCHD1 to treat incurable neurodevelopmental disorder PWS and muscular dystrophy FSHD.