Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard ....Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard tail), to describe the regrowth process and determine the abundance, location, functional properties and molecular control of the new lymphatics. Furthermore, if reptilian lymphatic growth factors can promote lymphangiogenesis in mammals, we can design novel therapeutic approaches using reptilian ligands to promote lymphangiogenesis in lymphoedematous human tissues.Read moreRead less
Investigation of Macrophage Function in an Immunologically Privileged Site. The unique phenotype of the testicular macrophage demands understanding, and this project has the potential to open up an entirely new direction of research. The basic information so generated could facilitate development of strategies to alter either host or donor tissue macrophage functions in order to prevent rejection responses in humans, and be used in the development of new anti-inflammatory drugs. Such technologie ....Investigation of Macrophage Function in an Immunologically Privileged Site. The unique phenotype of the testicular macrophage demands understanding, and this project has the potential to open up an entirely new direction of research. The basic information so generated could facilitate development of strategies to alter either host or donor tissue macrophage functions in order to prevent rejection responses in humans, and be used in the development of new anti-inflammatory drugs. Such technologies will have application in development of novel therapeutics for transplantation and the treatment of chronic inflammatory diseases. Read moreRead less
REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that th ....REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that the proteins also bind to each other and that calsequestrin regulates Ca2+ release from the stores through the ryanodine receptor ion channel. This regulation is likely to be important in conserving store calcium during stress or fatigue.Read moreRead less
Phospholipids and kinases as regulators of epithelial sodium channels. The intracellular signalling pathways that will be identified in this project will facilitate the development of novel therapies for the many conditions in which the activity of epithelial sodium channels is abnormal. These include influenza, otitis media, high blood pressure and cystic fibrosis. It will also provide training for post-doctoral fellows and research students in a number of the key techniques in modern cellular ....Phospholipids and kinases as regulators of epithelial sodium channels. The intracellular signalling pathways that will be identified in this project will facilitate the development of novel therapies for the many conditions in which the activity of epithelial sodium channels is abnormal. These include influenza, otitis media, high blood pressure and cystic fibrosis. It will also provide training for post-doctoral fellows and research students in a number of the key techniques in modern cellular physiology.Read moreRead less
Novel kinases: How do they regulate epithelial ion transport, and what is their role in epithelial function? The project will produce the knowledge of fundamental physiology that will lead to novel approaches for treating respiratory and gastrointestinal infections and cystic fibrosis, as well as for the accumulation of fluid in the lungs and abdomen that accompany many advanced malignancies. It thus has the potential to have a significant economic and social impact in Australia and internation ....Novel kinases: How do they regulate epithelial ion transport, and what is their role in epithelial function? The project will produce the knowledge of fundamental physiology that will lead to novel approaches for treating respiratory and gastrointestinal infections and cystic fibrosis, as well as for the accumulation of fluid in the lungs and abdomen that accompany many advanced malignancies. It thus has the potential to have a significant economic and social impact in Australia and internationally. Furthermore, it will provide advanced training in research methods to Australian scientists, equipping them to undertake challenging and interesting positions in the medical and life sciences and beyond.Read moreRead less
The Properties of Enteric Reflexes Recorded in Vivo. The benefit of the work will be a clear understanding of how a key body system, the digestive system is controlled. This will bring a new understanding of how intestinal function is influenced by the food that we eat and also by medicinal compounds. In the longer term, it may lead to development of dietary programs that improve digestive health and to ways to test for adverse or beneficial effects of drugs on the intestine.
Novel ways of regulating epithelial transport. This project is intended to discover novel intracellular mechanisms that regulate the rate of ion transport by the lung, the gut and the kidney. It will not only provide new insights into how the body controls a process that is critical to animal life, but also provide new targets for the development of pharmaceuticals.
A new model for secreton in epithelial cells. This proposal sets out to test a new model for secretion that we have developed in the light of recent experimental data. The project outcomes will advance our understanding of normal processes of secretion and may be important in understanding disease. We will develop cutting-edge techniques of microscopy which will place Australia at the forefront of this exciting field. The project will bring benefit to the Australian scientific community through ....A new model for secreton in epithelial cells. This proposal sets out to test a new model for secretion that we have developed in the light of recent experimental data. The project outcomes will advance our understanding of normal processes of secretion and may be important in understanding disease. We will develop cutting-edge techniques of microscopy which will place Australia at the forefront of this exciting field. The project will bring benefit to the Australian scientific community through interactions and collaborations with other scientists in Australia and internationally and will benefit early-career scientists, training them in novel methods and allowing them to develop their research expertise and profile and enabling them to compete on the world science stage. Read moreRead less