Probing the Tasmanian Devil Serum Proteome for Preclinical Diagnosis of Devil Facial Tumour Disease. The Tasmanian Devil (Sarcophilus harrisii) is a carnivorous marsupial endemic to the island state of Tasmania, and is found all over the state. Over the past decade, a dramatic decline has occurred in the Devil population in association with the emergence of Devil Facial Tumour Disease (DFTD). This project aims to develop a preclinical diagnostic test for DFTD that will provide vital information ....Probing the Tasmanian Devil Serum Proteome for Preclinical Diagnosis of Devil Facial Tumour Disease. The Tasmanian Devil (Sarcophilus harrisii) is a carnivorous marsupial endemic to the island state of Tasmania, and is found all over the state. Over the past decade, a dramatic decline has occurred in the Devil population in association with the emergence of Devil Facial Tumour Disease (DFTD). This project aims to develop a preclinical diagnostic test for DFTD that will provide vital information for use in developing management strategies to ensure the ongoing survival of the Tasmanian Devil. The benefit to Australia in performing this research rests in the new technology that will be developed and the application of this technology to key areas of national and international significance.Read moreRead less
Mechanisms controlling enteroendocrine hormone secretion in human duodenum. This project aims to gain a deeper understanding of nutrient sensing pathways present in enteroendocrine cells within the human intestine. These cells control digestive function, blood glucose levels and food intake and are thus critical to digestion. This project will endeavour to be the first to assess the biology of human enteroendocrine cells and will use innovative approaches to deeply assess function from the level ....Mechanisms controlling enteroendocrine hormone secretion in human duodenum. This project aims to gain a deeper understanding of nutrient sensing pathways present in enteroendocrine cells within the human intestine. These cells control digestive function, blood glucose levels and food intake and are thus critical to digestion. This project will endeavour to be the first to assess the biology of human enteroendocrine cells and will use innovative approaches to deeply assess function from the level of the individual to isolated enteroendocrine cells.Read moreRead less
A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project a ....A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project aims to use sensory neurons derived from human stem cells to develop and optimise assays that can be used to study the pharmacology and function of human sensory neurons in vitro. This enhances access to critical model systems and technology platforms and removes the need for isolation of cells from cadavers. Read moreRead less
Determination of the mechanisms of immune system regulation of inflammation by the human protein, chaperonin 10. The aim of this project is to determine the mechanisms by which a human protein, chaperonin 10 (Cpn10), regulates the immune system and suppresses inflammation. When cells of the human immune system are challenged with lipopolysaccharide (LPS) (a product of bacterial infection), the pro-inflammatory cytokine TNF is released. Cpn10 has been shown to suppress production of TNF on chall ....Determination of the mechanisms of immune system regulation of inflammation by the human protein, chaperonin 10. The aim of this project is to determine the mechanisms by which a human protein, chaperonin 10 (Cpn10), regulates the immune system and suppresses inflammation. When cells of the human immune system are challenged with lipopolysaccharide (LPS) (a product of bacterial infection), the pro-inflammatory cytokine TNF is released. Cpn10 has been shown to suppress production of TNF on challenge of cells with LPS, while increasing the levels of the anti-inflammatory cytokine IL-10. Investigating the role of Cpn10 in modulating inflammation will contribute to the understanding and treatment of diseases associated with inflammation, including multiple sclerosis and rheumatoid arthritis.Read moreRead less
Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not re ....Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not respond to the current TNF treatments. Improved anti-TNF strategies would provide enhanced health outcomes and welcome relief to many Australians. In addition, the economic benefit of the TNF market is very substantial. Therefore the potential impact of this research is very high both for health care and economical potential.Read moreRead less
The development of tyrosine kinase inhibitors for the treatment of inflammation and malignant disease. Through the combination of expertise from the Industry partner and the Hume group this project aims to develop specific inhibitors of the CSF-1 receptor protein tyrosine kinase in order to demonstrate their efficacy as modulators of CSF-1 dependent macrophage and tumour cell function in vitro. The expected outcome will be a lead set of targets which can be further assessed for therapeutic pote ....The development of tyrosine kinase inhibitors for the treatment of inflammation and malignant disease. Through the combination of expertise from the Industry partner and the Hume group this project aims to develop specific inhibitors of the CSF-1 receptor protein tyrosine kinase in order to demonstrate their efficacy as modulators of CSF-1 dependent macrophage and tumour cell function in vitro. The expected outcome will be a lead set of targets which can be further assessed for therapeutic potential in clinical trials.Read moreRead less
Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in ....Targeted development of dual action antitumour and antiangiogenic agents using differential and functional proteomics. There is an enormous need to develop more effective and less toxic therapeutic approaches to reduce the social and economic burden of cancer. The recent identification of small molecules that can act by both destroying cancer cells and the blood vessels that carry nutrients to them has provided a unique opportunity to define the pathways involved in the action of these agents in order to develop more potent drug analogues. Development of these molecules will involve a collaborative and multidisciplinary link with our industry partner and the use of frontier technologies that may lead to improved health and economic outcomes for Australia. Read moreRead less
A proteomic approach to identifying the signaling pathway(s) by which acute oxidative stress causes cell death by apoptosis. Oxidative stress following traumatic injury (heart attack or stroke) is known to activate signaling pathways leading to programmed cell death (apoptosis). The aim of this project is to develop methods to identify the signaling proteins involved. Identifying proteins involved in causing cell death will be useful in developing diagnostic tools as well as providing potential ....A proteomic approach to identifying the signaling pathway(s) by which acute oxidative stress causes cell death by apoptosis. Oxidative stress following traumatic injury (heart attack or stroke) is known to activate signaling pathways leading to programmed cell death (apoptosis). The aim of this project is to develop methods to identify the signaling proteins involved. Identifying proteins involved in causing cell death will be useful in developing diagnostic tools as well as providing potential therapeutic possibilities.Read moreRead less
Life at the nanometre scale: imaging immunological synapses with a novel super-resolution fluorescence microscope. This project aims to image individual proteins in activated white blood cells in order to understand how lymphocytes participate in an immune response. The problem is that current imaging modalities either lack resolution or are unsuitable for live cell and three-dimensional (3D) imaging. With the project’s industry partner, Carl Zeiss MicroImaging, the project will build and apply ....Life at the nanometre scale: imaging immunological synapses with a novel super-resolution fluorescence microscope. This project aims to image individual proteins in activated white blood cells in order to understand how lymphocytes participate in an immune response. The problem is that current imaging modalities either lack resolution or are unsuitable for live cell and three-dimensional (3D) imaging. With the project’s industry partner, Carl Zeiss MicroImaging, the project will build and apply a novel microscope that is capable of visualising single proteins in 3D and live cells. This technology will provide insights into signalling and lymphocyte function on a true molecular scale.Read moreRead less
Rational structure-based drug design of protein tyrosine kinase inhibitors. Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune-related disorders, that cause significant morbidity and mortality within the population. This research proposal aims to develop PTK-specific small molecule inhibitors to combat such diseases. Cytopia's drug discovery capability, coupled with the X-ray crystallographic expertise within Monas ....Rational structure-based drug design of protein tyrosine kinase inhibitors. Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune-related disorders, that cause significant morbidity and mortality within the population. This research proposal aims to develop PTK-specific small molecule inhibitors to combat such diseases. Cytopia's drug discovery capability, coupled with the X-ray crystallographic expertise within Monash University, will permit a rational, structure-based drug discovery platform to be established. The ultimate goal of this innovative and mutlidisciplinary approach, namely a portfolio of phase I therapeutics, will be of substantial benefit in the medical health area.Read moreRead less