A proteomic approach to the identification of novel targets for allergy treatment. Eosinophils are involved in parasite immunity and in the pathology of allergic diseases including asthma. Eosinophil recruitment and activation is critical to their functional activity, but the relevant molecular mechanisms have not been fully elucidated. In the present proposal, a unique resource of eosinophils, at different stages of recruitment and activation, will be used for detailed proteomic analysis to ide ....A proteomic approach to the identification of novel targets for allergy treatment. Eosinophils are involved in parasite immunity and in the pathology of allergic diseases including asthma. Eosinophil recruitment and activation is critical to their functional activity, but the relevant molecular mechanisms have not been fully elucidated. In the present proposal, a unique resource of eosinophils, at different stages of recruitment and activation, will be used for detailed proteomic analysis to identify molecules and molecular pathways involved in eosinophil migration and activation. These studies may lead to novel anti-inflammatory strategies and more targeted drug treatments that will generate significant intellectual property and be of enormous benefit to allergy patients worldwide.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
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
Proteomics Analysis of Interactions Between Chaperonin 10 and Cell Surface Proteins. Specific interactions at the cell surface may induce downstream biological responses. In the case of chaperonin 10, Cpn10, interaction at the cell surface results in immunomodulation of the inflammatory response. Cell surface proteins that interact with Cpn10 have not been identified. This project will use chemical crosslinking and proteomic techniques to identify cell surface proteins that interact with Cpn10 a ....Proteomics Analysis of Interactions Between Chaperonin 10 and Cell Surface Proteins. Specific interactions at the cell surface may induce downstream biological responses. In the case of chaperonin 10, Cpn10, interaction at the cell surface results in immunomodulation of the inflammatory response. Cell surface proteins that interact with Cpn10 have not been identified. This project will use chemical crosslinking and proteomic techniques to identify cell surface proteins that interact with Cpn10 and structural features of Cpn10 involved in these interactions. These findings will providde leads for the development of immunomodulatory therapeutics based on Cpn10 interactions. Analytical technologies will be developed that are applicable to other interacting protein systems.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
Rational structure-based drug design of protein tyrosine kinase inhibitors. This research project is focussed on understanding the physiological roles of a group of enzymes within the cell, as well as developing therapeutics to combat significant diseases. It will achieve this by developing compounds to enzymes that are implicated in the disease process. The research project represents a continuation of a collaboration between academic researchers at Monash University, and an Australian biotec ....Rational structure-based drug design of protein tyrosine kinase inhibitors. This research project is focussed on understanding the physiological roles of a group of enzymes within the cell, as well as developing therapeutics to combat significant diseases. It will achieve this by developing compounds to enzymes that are implicated in the disease process. The research project represents a continuation of a collaboration between academic researchers at Monash University, and an Australian biotechnology company, Cytopia Ltd.Read moreRead less
Investigating the atomic structure of an immune cell inhibitory receptor. T cells play a key role in the adaptive immune system, whose reactivity must be controlled to prevent aberrant reactivity. Central to the function of T cells is the T cell antigen receptor, and a host of co-stimulatory molecules, co-receptors and inhibitory receptors. This proposal, in partnership with Immutep Ltd, aims to gain a basic understanding of the structure and function of a key inhibitory receptor found on T cel ....Investigating the atomic structure of an immune cell inhibitory receptor. T cells play a key role in the adaptive immune system, whose reactivity must be controlled to prevent aberrant reactivity. Central to the function of T cells is the T cell antigen receptor, and a host of co-stimulatory molecules, co-receptors and inhibitory receptors. This proposal, in partnership with Immutep Ltd, aims to gain a basic understanding of the structure and function of a key inhibitory receptor found on T cells, termed the Lymphocyte activation gene-3 (LAG-3). The proposal utilises a combination of cellular immunology and structural biology to gain insight into the form and function of the LAG-3 molecule. Ultimately this fundamental knowledge can be used by the biotechnology industry.Read moreRead less
Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell recept ....Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell receptor is determined by utilising structural biology and cellular immunology techniques. The impact of this project effects the development of innovative T cell immunomodulatory agents, improving the health and quality of life of the Australian population.Read moreRead less
Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, an ....Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, and what target molecules they act on. A better understanding of these factors will increase the chances of finding cures and developing better treatments for important inflammatory diseases of the ageing population.Read moreRead less
Modulating T cell responses with novel Lck activating compounds. Modulating T cell responses with novel Lck activating compounds. This project aims to research T cell receptor (TCR) signal initiation and network plasticity and identify uses for drugs that affect the kinase Lck. The TCR signalling network has considerable plasticity so that modulation of one molecule (here the drug target is Lck) can have non-linear effects on T cell function. This project intends to use novel drugs to understand ....Modulating T cell responses with novel Lck activating compounds. Modulating T cell responses with novel Lck activating compounds. This project aims to research T cell receptor (TCR) signal initiation and network plasticity and identify uses for drugs that affect the kinase Lck. The TCR signalling network has considerable plasticity so that modulation of one molecule (here the drug target is Lck) can have non-linear effects on T cell function. This project intends to use novel drugs to understand how the T cell network can be exploited to control both the magnitude and quality of the T cell responses. This research is expected to aid the design of immune-modulating drugs.Read moreRead less