Functional Contribution Of Fetal Microchimeric Cells In Transgenic Models Of Maternal Tissue Repair In And After Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Fetal stem cells cross into the mother during pregnancy and persist lifelong in her tissues. To determine whether helpful or harmful, we will study how these cells contribute to healing both after acute injury and in chronic genetic models like brittle-bone disease and muscular dystrophy. This research will inform long-term consequences of pregnancy, important for women's health and longevity, and help develop a promising form of stem cell therapy.
A Phase I Study Of PiggyBac CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Persistent And Relapsed B-cell Leukaemia And Lymphoma Post Allogeneic Stem Cell Transplantation (The CARTELL Study).
Funder
National Health and Medical Research Council
Funding Amount
$357,590.00
Summary
Most people with relapsed leukaemia and lymphoma after bone marrow transplant die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but there is little experience in bone marrow transplant patients. We will make leukaemia and lymphoma specific immune cells from normal bone marrow transplant donors, then administer the immune cells to transplant patients to assess their safety and effectiveness.
Modelling TRPV4 Skeletal Disorders Using Human IPSCs
Funder
National Health and Medical Research Council
Funding Amount
$1,171,187.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and new in vitro re-programing technology to induce them to form cartilage cells to produce “disease in a dish” models of human skeletal disorders. These models will allow us to answer questions about how specific mutations cause disease and identify potential therapies
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Controlling the adhesome to regulate cell fate on biomaterials. Mesenchymal stem cell-based tissue engineering practices are hampered worldwide by the lack of appreciation and understanding of the matrix-mediated cues that must be provided during adhesion and spreading to drive cells to definitive tissue end points. This project will address these knowledge deficiencies by combining high throughput array technologies, a set of tailorable self-assembling biomaterials and real-time biosensors to r ....Controlling the adhesome to regulate cell fate on biomaterials. Mesenchymal stem cell-based tissue engineering practices are hampered worldwide by the lack of appreciation and understanding of the matrix-mediated cues that must be provided during adhesion and spreading to drive cells to definitive tissue end points. This project will address these knowledge deficiencies by combining high throughput array technologies, a set of tailorable self-assembling biomaterials and real-time biosensors to rapidly, at high resolution, elucidate how mechanotransductive cues determine the fate choice of mesenchymal stem cells, and furthermore, how to manipulate them with smart biomaterial design to achieve desired outcomes for tissue engineering. Read moreRead less
Dual Targeting Of The Androgen Receptor For Effective And Durable Control Of Lethal Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$946,177.00
Summary
Preventing binding of androgens to the androgen receptor is the mainstay treatment for advanced prostate cancer, but resistance inevitably develops and the disease becomes lethal. We will develop a new drug that targets a part of the androgen receptor unrelated to its androgen binding function to overcome resistance to current therapy. As this drug will be effective in all stages of prostate cancer, it has high potential to improve survival outcomes for men with prostate cancer.