Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis. Cyclic Adenosine Monophosphate (cAMP) is an important cellular chemical necessary for cell growth. However, de-regulated cAMP production in response to altered physiology can result in cellular death or apoptosis. This is attributed to the development of certain human diseases and this project aims to understand the molecular mechanism behind this process.
Elucidating the regulation of cell death by random mutagenesis of key apoptotic proteins. All organisms need to remove damaged or excessive cells. This cell death process is called apoptosis. Defects in apoptosis result in numerous diseases including cancer, and neurodegenerative and immune disorders. Determining how this process is regulated is of crucial importance for therapeutic intervention. We will utilise a powerful strategy to mutate proteins required for apoptosis so that they no longer ....Elucidating the regulation of cell death by random mutagenesis of key apoptotic proteins. All organisms need to remove damaged or excessive cells. This cell death process is called apoptosis. Defects in apoptosis result in numerous diseases including cancer, and neurodegenerative and immune disorders. Determining how this process is regulated is of crucial importance for therapeutic intervention. We will utilise a powerful strategy to mutate proteins required for apoptosis so that they no longer work, which will allow the identification of protein regions essential for cell death activity . This will lead to identification of potential drug targets to control apoptosis. Elucidating the mechanism of cell death will lead to the development of novel and improved therapies for diseases such as cancer and neurodegenerative disease.Read moreRead less
Determining the molecular regulation of blood vessel development and angiogenesis. Abnormal blood vessel growth is associated with diseases including cancer, macular degeneration, diabetic retinopathy and chronic inflammation. This project focuses on understanding normal blood vessel growth in order to gather clues to help discover ways of preventing abnormal blood vessel growth during disease.
Molecular control of apoptosis and protein homeostasis. A million cells are produced every second by cell division. At the same time a million cells commit suicide by a process called apoptosis. When cells fail to die when they should they can develop into cancers. In heart attacks, stroke and neurodegenerative diseases, many cells appear to activate their self destruct mechanism to die unnecessarily. Drugs that can cause cancer cells to kill themselves, or drugs that prevent cells dying when th ....Molecular control of apoptosis and protein homeostasis. A million cells are produced every second by cell division. At the same time a million cells commit suicide by a process called apoptosis. When cells fail to die when they should they can develop into cancers. In heart attacks, stroke and neurodegenerative diseases, many cells appear to activate their self destruct mechanism to die unnecessarily. Drugs that can cause cancer cells to kill themselves, or drugs that prevent cells dying when they shouldn't, would make a major impact on many important diseases. Understanding the molecular mechanisms of cell death is the first step towards developing these drugs.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100117
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Allosteric fingerprinting of G protein-coupled receptor monomers and oligomers. Allosteric modulation describes interactions between distinct, but conformationally linked, binding sites. Research will develop enabling technology using the unique profile, or 'fingerprint', of allosteric modulation at interacting and non-interacting G protein-coupled receptors to probe for receptor complexes within healthy and diseased tissue.
Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiati ....Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiating (stem cell) property of tumour cells is maintained offers potential novel avenues to eliminate persistent cancer cells. This knowledge will ultimately lead to better management and treatment of cancer, and increase survival. An understanding of stem cell behaviour is also central to the control of degenerative conditions.Read moreRead less
Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australia ....Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australians.Read moreRead less
Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase ....Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase 3 (HDAC3) as potentially involved in promoting colon cancer. The current proposal will now extend and validate this finding in mice. Importantly, drugs which inhibit HDAC3 have recently been developed for the treatment of cutaneous T-cell lymphoma. Defining the role HDAC3 plays in colon cancer will justify testing these drugs in colon cancer patients.Read moreRead less
Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family protei ....Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family proteins in spermatogenesis. The outcomes will define the different roles of highly similar proteins from the same family in differentiation of a single cell lineage. This is important in generating functional tissues using in vitro laboratory approaches or understanding how normal development and developmental disorders arise.Read moreRead less
Controlling apoptotic cell death in health and disease. Regulating how and when cells die is crucial for the development and maintenance of a healthy body and mind. This project will investigate the proteins that are responsible for controlling cell death with the view to identifying novel ways to target these proteins for the treatment of disorders such as cancer, neurodegenerative disease and autoimmunity.