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    A Comprehensive Immunoproteomic Analysis Of The Repertoire And Dynamics Of Human Antibody Responses To Malaria

    Funder
    National Health and Medical Research Council
    Funding Amount
    $325,384.00
    Summary
    Malaria infects 10% of humanity and kills more than two million children annually. We have developed a powerful new approach to comprehensively profile antibody responses against the malaria parasite in PNG children during the critical period of development of disease immunity. The proposed work will help us to better understand the targets and mechanisms of naturally acquired immunity and prioritise the development of future thereapeutic vaccines, drugs or diagnostics.
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    A Novel Mode Of Cytokine Receptor Assembly And Activation: Functional And Structural Characterization

    Funder
    National Health and Medical Research Council
    Funding Amount
    $621,322.00
    Summary
    This proposal will study a group of protein hormones and their receptors, implicated in blood cell cancers and inflammatory diseases and for which current treatments are inadequate. We will determine the mechanism of receptor activation and in particular will seek to link different forms of receptor assembly to different functions. This information will help us develop new drugs with more specificity for certain hormone functions and thus less side effects
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    Funded Activity

    Structural Biology Of Cytokine Receptor Signalling

    Funder
    National Health and Medical Research Council
    Funding Amount
    $3,988,996.00
    Summary
    This Program will be focused on a group of protein hormones and their receptors, implicated in blood cell cancers and inflammatory diseases and for which current treatments are inadequate. We will determine the mechanism of receptor activation and in particular will seek to link different forms of receptor assembly to different functions. This information will help us develop new drugs with more specificity for certain hormone functions and thus less side-effects.
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    Funded Activity

    Structural Studies On The Conjugative Apparatus Of The Gram-positive Bacteria, Clostridium Perfringens.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $287,321.00
    Summary
    Antibiotic resistance is a worldwide health problem. It has severely reduced the effectiveness of many antibiotics driving up the health care costs and death rates associated with bacterial infections. This project aims to investigate how antibiotic resistance determinants are transferred in the pathogenic bacteria, Clostridium perfringens. By understanding the mechanism of antibiotic resistance transfer in bacteria we will be better armed to combat antibiotic resistance.
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    Funded Activity

    Regulation Of Endothelin Converting Enzyme Subcellular Distribution And Vascular Endothelin Production.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $41,321.00
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    Funded Activity

    Zinc Fingers As Pharmaceutical Scaffolds

    Funder
    National Health and Medical Research Council
    Funding Amount
    $482,640.00
    Summary
    Great advances have been made in pharmaceutical design and discovery over the last 50 years. While drugs have traditionally been discovered using random screening of natural product libraries and chemical databases, new technologies in protein chemistry, structural and molecular biology have been adopted in efforts to speed the drug design process and increase its hit rate. In addition, our rapidly increasing knowledge of the molecular causes of many diseases provides us with many opportunities .... Great advances have been made in pharmaceutical design and discovery over the last 50 years. While drugs have traditionally been discovered using random screening of natural product libraries and chemical databases, new technologies in protein chemistry, structural and molecular biology have been adopted in efforts to speed the drug design process and increase its hit rate. In addition, our rapidly increasing knowledge of the molecular causes of many diseases provides us with many opportunities to develop therapeutics directed towards known molecular targets. Nevertheless, despite these advances, problems such as drug resistance and toxic side effects that compromise drug efficacy make it clear that there is a need for new classes of drugs with different modes of action. Because of their favourable properties, small-molecule drugs comprise by far the largest class of currently available therapeutics. However, in many cases, a drug derived from a protein may be preferable. The development of protein-based drugs is a youthful and rapidly expanding area of biotechnology, but to date, most studies have focused on targeting pathological events that occur on the outside of cells. We propose to use a combination of methods from molecular and structural biology, together with recently developed high-throughput screening techniques, to develop a generic protein drug scaffold that can be used as a template to develop therapeutics against a wide range of inappropriate interactions that may occur between molecules within cells.
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    Affinity-based Profiling Of Bacterial Fe(III)-siderophore Receptors: Design Strategies For Antibiotics And Iron Overload

    Funder
    National Health and Medical Research Council
    Funding Amount
    $275,016.00
    Summary
    In order to establish an infection, bacteria compete with the host for iron, which is in scarce supply. To access iron, bacteria produce compounds called siderophores which bind iron strongly. The iron-siderophore complex, which is unique to each bacterium, is recognised by specific receptors at the bacterial cell-surface and imported for use. In this project, we are using modified siderophores as platforms for bacteria-specific drug design with the aim of producing new antibiotics.
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    Funded Activity

    Colon Cancer: Receptors, Signalling And Therapeutics

    Funder
    National Health and Medical Research Council
    Funding Amount
    $7,115,542.00
    Summary
    This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell gr .... This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell growth, survival and movement. Newly developed instruments and techniques will allow us to identify and detect the critical steps during the development of colorectal cancer and to design potent drugs to fight the disease. We have experience in conducting novel clinical trials in colon cancer and have developed imaging techniques for monitoring the effectiveness and safety of new anti-cancer drugs. Our collective scientific experience and ability to work in the clinic provides a unique opportunity for developing more effective treatments for colorectal cancer patients.
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    Funded Activity

    Exploring The Structure Activity Relationships Of Novel Trypsin Inhibitor SFTI-1 With Implications As Cancer Therapeutic

    Funder
    National Health and Medical Research Council
    Funding Amount
    $360,312.00
    Summary
    A novel peptide isolated from sunflower seeds has recently been shown to interact with an enzyme implicated in the growth of cancers and in particular prostate cancer. The proposed research involves developing this peptide as a therapeutic by performing a thorough analysis of the important features involved in its exciting anti-cancer activity.
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    Funded Activity

    Design And Synthesis Of Peptide - Based Drugs For Multiple Sclerosis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $351,000.00
    Summary
    Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that affects ~1 million young adults worldwide. It is a debilitating disease for which there is currently no cure. The most effective treatment available, interferon-b (IFN-b) is useful for the treatment of some forms of the disease, reducing the relapse rate, that is the frequency of attacks or exacerbations of the disease, and delaying the time to onset of sustained progression of the disability. This treatment ma .... Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that affects ~1 million young adults worldwide. It is a debilitating disease for which there is currently no cure. The most effective treatment available, interferon-b (IFN-b) is useful for the treatment of some forms of the disease, reducing the relapse rate, that is the frequency of attacks or exacerbations of the disease, and delaying the time to onset of sustained progression of the disability. This treatment may, however, cause adverse side effects, result in the development of antibodies that neutralise its function and is prohibitively expensive. In addition it does not slow the sustained progression of the disease in 20-40% of patients with the two most common types of MS and does not appear to directly affect deterioration of the protective layer around neurons, myelin. There is clearly a need for the development of therapeutics that address these issues and the drug leads to be developed in this project may help to overcome some of these shortfalls. While the immune system of a healthy individual is able to distinguish between foreign molecules and its own molecules, in MS the immune system fails to do this. An immune response against important proteins that form part of the protective myelin layer around neurons occurs. This means that the integrity of the protective layer is compromised. The peptide-based drugs that we plan to develop in this project are designed to interfere with the interaction between these important myelin proteins and their immune system targets. This will leave the myelin proteins to carry out their normal physiological roles and should therefore significantly slow, if not halt, progression of the disease. Given the prevalence of MS such a development could have a profound impact on the health and quality of life of many individuals and their families, and has the potential to substantially reduce the economic burden of this disease on the community.
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