Structural And Functional Studies On RNA Nuclear Retention Mediated By Paraspeckles: A Novel Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$290,978.00
Summary
Dynamic interactions between proteins and nucleic acids are essential process in gene regulation, where aberrant regulation leads to various diseases including cancers. The project aims to examine the interactions between paraspeckle proteins and nucleic acid molecules via determination of the structures of protein-nucleic acid complexes at the atomic level. The results will provide a better understanding of a recently discovered gene regulation mechanism and a basis for new gene therapy.
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Sugar transporters in coral symbiosis and origin of parasitism. We aim to identify how symbiotic algae feed sugar to their coral hosts. Corals need this algal sugar to exist, but no one knows how it is transferred, so understanding this crucial mechanism is hugely significant. The first benefit of this research will be a fundamental understanding about how two organisms (algae and coral) cooperate to build habitats like the Great Barrier Reef. We also aim to explore whether coral/algal coopera ....Sugar transporters in coral symbiosis and origin of parasitism. We aim to identify how symbiotic algae feed sugar to their coral hosts. Corals need this algal sugar to exist, but no one knows how it is transferred, so understanding this crucial mechanism is hugely significant. The first benefit of this research will be a fundamental understanding about how two organisms (algae and coral) cooperate to build habitats like the Great Barrier Reef. We also aim to explore whether coral/algal cooperation paved the way for the origin of parasitism. The second key outcome will be to identify the precise molecular mechanism that allowed parasitism to arise. This will benefit us through understanding the origins of important diseases such as human malaria and related infections of livestock and wildlife.
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Transport And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$592,023.00
Summary
Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transpor ....Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transported within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins and how the virus escapes from nerves to infect skin and cause disease. Such information on viral transport will allow development of inhibitors of this process which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities. Finally this data will assist in understanding similar mechanisms for other viruses transported in nerve cells such as those causing shingles and rabies.Read moreRead less
Sugars in the real world: are cultured cancer cells a good model system for studying protein glycosylation? It is challenging to study errors in metabolism in human beings, so researchers use cells grown in the laboratory to understand disease processes. This project will determine if cultured cells accurately reflect the real changes to cell surface sugars that occur in all cancers, and the effect of these changes on the invasive properties of colon cancer cells.
Future Industries Research - Biotechnology and Nanotechnology: Small talk: Communication networks in microbes. We will use the Australian Proteome Analysis Facility to address the multifaceted mechanisms of microbial interactions and produce new knowledge about the pathogen Pseudomonas aeruginosa, a common cause of death in cystic fibrosis patients. We will characterise the interactions between P. aeruginosa and the emerging fungal pathogen Scedosporium aurantiacum as a proactive step towards be ....Future Industries Research - Biotechnology and Nanotechnology: Small talk: Communication networks in microbes. We will use the Australian Proteome Analysis Facility to address the multifaceted mechanisms of microbial interactions and produce new knowledge about the pathogen Pseudomonas aeruginosa, a common cause of death in cystic fibrosis patients. We will characterise the interactions between P. aeruginosa and the emerging fungal pathogen Scedosporium aurantiacum as a proactive step towards better understanding of pathogen communication. Improved understanding of pathogen interactions should facilitate the development of novel anti-adhesives as therapeutics. Our project will train young scientists in a new integrated approach to biology.Read moreRead less
What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dy ....What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dying from viruses; however, it is not known what is cause and effect. This project will clarify Varroa’s exact role in the evolution of virulence in RNA viruses. The intended outcome is increased knowledge allowing the design of an effective treatment to prevent the death of honeybee colonies.Read moreRead less
Glycine Transporters regulate the concentration of glycine in the spinal cord and brain. It has been suggested that elevating glycine levels in these regions may be useful in treating pain and schizophrenia. This project will provide the basis for the development of new glycine transport inhibitors that may be used to treat these conditions.
Understanding glycopolymer interactions with the extracellular matrix. This project aims to advance knowledge of the biochemical and biophysical structure of the endothelial glycocalyx, a dynamic cell surface extracellular matrix rich in proteoglycans and glycosaminoglycans. It will be the first to explore how charged glycopolymers interact with this dynamic interface with the goal to develop a model of the glycocalyx lifecycle. This project is expected to enable the transfer of skills, knowledg ....Understanding glycopolymer interactions with the extracellular matrix. This project aims to advance knowledge of the biochemical and biophysical structure of the endothelial glycocalyx, a dynamic cell surface extracellular matrix rich in proteoglycans and glycosaminoglycans. It will be the first to explore how charged glycopolymers interact with this dynamic interface with the goal to develop a model of the glycocalyx lifecycle. This project is expected to enable the transfer of skills, knowledge and ideas as well as advanced research and industrial training for young scientists. Knowledge derived from this project is expected to enable future innovation in molecules with tailored interactions with the glycocalyx with significant benefits for researchers, manufacturers and end users. Read moreRead less