Regulation Of Secretion Of The Fungal Virulence Determinant, Phospholipase B
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted ....Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted by the disease-causing fungus, Cryptococcus neoformans, and that it is important in enabling the fungus to invade the host's cells and spread around the body from the lungs to the brain, where it can cause meningoencephalitis. PLB is also produced by other disease-causing fungi. The mechanism of PLB secretion is completely unknown. In this project we aim to determine the pathways involved in PLB secretion with the intention of exploiting steps unique to pathogenic fungi, for the future design of new anti-fungal drugs.Read moreRead less
Discovery And Development Of Better Pain Treatments
Funder
National Health and Medical Research Council
Funding Amount
$9,613,850.00
Summary
Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clini ....Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clinical potential.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668534
Funder
Australian Research Council
Funding Amount
$770,000.00
Summary
High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Anal ....High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Analysis Facility (APAF). The new technology is a missing link in bioanalytical capability where other instruments are not sufficiently sensitive. The instrument will be managed by MS specialists at the Bioanalytical Mass Spectrometry Facility at UNSW (www.bmsf.unsw.edu.au) where access by and training of users is well established.Read moreRead less
Development of chaperonin 10-based second generation biopharmaceuticals for treatment of inflammatory diseases. Diseases caused by malfunctioning of the body's immune system (inflammatory diseases) such as rheumatoid arthritis, psoriasis and Crohn's disease cause illness in all cultures and societies, and impose financial strain on health care providers. Current treatment relies on biopharmaceuticals that block inflammatory mediators in the body or with pharmaceuticals such as anti-inflammatory ....Development of chaperonin 10-based second generation biopharmaceuticals for treatment of inflammatory diseases. Diseases caused by malfunctioning of the body's immune system (inflammatory diseases) such as rheumatoid arthritis, psoriasis and Crohn's disease cause illness in all cultures and societies, and impose financial strain on health care providers. Current treatment relies on biopharmaceuticals that block inflammatory mediators in the body or with pharmaceuticals such as anti-inflammatory drugs; both these treatments may have serious side effects. Cpn10 suppresses the body's inflammatory response while maintaining immune function to combat infections. The project seeks to develop new, safe and effective biopharmaceuticals based on Cpn10 for the treatment of a variety of chronic inflammatory diseases and autoimmune disorders.Read moreRead less
Indoleamine 2,3-dioxygenase-2: a newly discovered enzyme with a key role in kidney function. We have discovered an enzyme, IDO2, that metabolises the amino acid tryptophan. The enzyme is found in kidney tubule cells and we propose that IDO2 activity regulates sodium reabsorption by the renal tubular cells. Regulation of sodium balance is important for determining blood pressure in health and disease.
Characterization of erythroid differentiation related factor (EDRF): a novel a-globin binding protein. Hemoglobin, a four-subunit protein comprising two alpha and two beta polypeptide chains, is the essential oxygen transporter found in all mammals. Problems with the synthesis of hemoglobin can give rise to a range of common and serious human disorders, including thalassaemia and anemia. We have discovered a protein, EDRF, that appears to interact directly with alpha-globin (but not beta-globin) ....Characterization of erythroid differentiation related factor (EDRF): a novel a-globin binding protein. Hemoglobin, a four-subunit protein comprising two alpha and two beta polypeptide chains, is the essential oxygen transporter found in all mammals. Problems with the synthesis of hemoglobin can give rise to a range of common and serious human disorders, including thalassaemia and anemia. We have discovered a protein, EDRF, that appears to interact directly with alpha-globin (but not beta-globin) and to play a role in the regulation of hemoglobin production. We now seek to understand the nature of this interaction at a molecular level and mechanistic level.Read moreRead less
Biomimetic Insights from Enamel: A Nano-mechanical and Nano-structural Investigation of a Natural Ceramic-like Biocomposite. Enamel is a naturally developed example of an optimised material structure that constitutes the hardest tissue in the human body. In addition it is exposed to severe mechanical and environmental challenges and must last the lifetime of the individual and unlike other tissue is unable to heal or repair itself. Understanding the factors controlling the amazing mechanical pr ....Biomimetic Insights from Enamel: A Nano-mechanical and Nano-structural Investigation of a Natural Ceramic-like Biocomposite. Enamel is a naturally developed example of an optimised material structure that constitutes the hardest tissue in the human body. In addition it is exposed to severe mechanical and environmental challenges and must last the lifetime of the individual and unlike other tissue is unable to heal or repair itself. Understanding the factors controlling the amazing mechanical properties of this tissue will be of great benefit for the design of bio-inspired materials and be important for the development of advanced materials for which Australia already has an enviable reputation.Read moreRead less
Molecular and immunological approaches to managing Australia's seafood allergy epidemic. Seafood is an increasingly important cause of food allergy. Novel insight into the functions of why and how proteins from seafood develop to potent allergens will lead to the development of better diagnostics and therapeutics. This will assist patients to better manage their serious food allergy.