Defining The Mechanism Of Assembly Of Herpes Simplex Virus In The Neuronal Growth Cone And Its Subsequent Exit To Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$774,624.00
Summary
Herpes simplex virus (HSV) causes dormant infection of nerve cell bodies near the spine. It periodically reactivates to be transported along nerves to the skin where it causes oral, genital or neonatal herpes and mediates HIV superinfection. HSV assembles into its final form in the terminal part of the axon just prior to crossing into skin. Elucidating the mechanism of HSV assembly and exit will facilitate new strategies for antiviral agents and immune treatment for HSV and similar viruses.
The Mechanism Of HSV-1 Transport In Sensory Axons And Its Unique Assembly At The Axon Terminus
Funder
National Health and Medical Research Council
Funding Amount
$670,284.00
Summary
Herpes simplex viruses 1 and 2 cause common diseases such as genital herpes and, occasionally, neonatal deaths and encephalitis and predisposes to HIV infection. New antiviral strategies are required for resistant viruses for control. These aims will be facilitated by understanding how HSV is transported down nerves and across into skin. In this study, we will define how a key viral protein plays a major role in assembly of the virus at the tip of the nerve before it enters skin.
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
Mechanisms Of Oxidised Protein Accumulation In Ageing Cells
Funder
National Health and Medical Research Council
Funding Amount
$429,000.00
Summary
Australia has one of the world's most rapidly ageing populations. It is estimated that in 30 years time over 30% of the population will be over 65; many will suffer from a debilitating, age-related disease. The diseases of ageing represent one of the major health challenges this century. Despite their increasing incidence, our understanding of the underlying causes is limited. A common feature is the accumulation of damaged proteins in cells and tissues. Damaged proteins are usually broken down ....Australia has one of the world's most rapidly ageing populations. It is estimated that in 30 years time over 30% of the population will be over 65; many will suffer from a debilitating, age-related disease. The diseases of ageing represent one of the major health challenges this century. Despite their increasing incidence, our understanding of the underlying causes is limited. A common feature is the accumulation of damaged proteins in cells and tissues. Damaged proteins are usually broken down by the cells and replaced, but in many age-related diseases this process fails. The most common source of protein damage is attack by oxygen-derived free radicals. These are by-products of our body's need for oxygen and can originate from atmospheric pollutants. Oxygen rusts metal, makes fat go rancid and can cause irreparable damage to proteins and other biological molecules. Free radical damage contributes to the development of many age-related diseases such as atherosclerosis and neurodegenerative diseases such as Alzheimer's disease. The accumulation of damaged proteins can cause cell death. Our knowledge of the mechanisms by which cells remove proteins damaged by oxygen and the reasons for their accumulation is limited. In this project we will use a novel technique we have developed to generate oxidised proteins in ageing cells. We will identify cellular mechanisms required for the efficient removal of damaged proteins and those mechanisms which fail in ageing cells. We will focus on a group of proteins which protect damaged proteins from aggregating and accumulating and we will examine how we can prevent the accumulation of oxidised proteins by stimulating the body s defence mechanisms. Since the population of Australia is ageing, diseases of ageing are going to consume an increasing amount of the national health budget. A better knowledge of these cellular mechanisms will allow us to design effective prevention and treatment strategies which are at present lacking.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
Discovery Early Career Researcher Award - Grant ID: DE190100985
Funder
Australian Research Council
Funding Amount
$409,574.00
Summary
Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes wit ....Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes with high efficacy and specificity. This project will provide new and intriguing insights into cellar function, with broad applications in basic research and biotechnology.Read moreRead less