Maintaining fidelity in viral Ribonucleic acid (RNA) polymerases. This project will provide informed insights into the dynamics of viruses that currently impact a healthy start to life, ageing well and productively, and preventative healthcare. The analysis of viruses that cause gastroenteritis outbreaks will increase our understanding of how these viruses replicate and spread.
Noncoding RNAs of insect-specific flaviviruses: biogenesis and functions. This project aims to investigate noncoding RNAs (sfRNAs) of insect-specific flaviruses (ISFs). These RNAs are produced from viral RNA by host ribonuclease and play important role in pathogenesis and transmission of vertebrate-infecting flaviviruses (VIFs). The team has shown that ISFs also produce sfRNAs although likely employing a different mechanism. The project expects to generate new knowledge on ISF sfRNA biogenesis a ....Noncoding RNAs of insect-specific flaviviruses: biogenesis and functions. This project aims to investigate noncoding RNAs (sfRNAs) of insect-specific flaviruses (ISFs). These RNAs are produced from viral RNA by host ribonuclease and play important role in pathogenesis and transmission of vertebrate-infecting flaviviruses (VIFs). The team has shown that ISFs also produce sfRNAs although likely employing a different mechanism. The project expects to generate new knowledge on ISF sfRNA biogenesis and functions using combination of modern structural, biochemical, and innovative molecular virology methods. The outcome will be a clearer understanding of processes governing flavivirus host restriction and evolution. This will improve understanding of virus-host interactions and train students in cutting edge techniques.Read moreRead less
Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be diff ....Detection of imported exotic strains of West Nile virus for national biosecurity surveillance. West Nile virus (WNV) is transmitted by mosquitoes and causes a fatal disease of the brain in animals and humans. WNV is currently exotic to this country, however a closely related, but benign cousin of this virus (Kunjin) can be found in Northern Australia. Currently it is very difficult to differentiate between infections with WNV and Kunjin using standard laboratory tests, therefore it will be difficult for public health officials to detect WNV if it is introduced to Australia. In this project we aim to develop more accurate laboratory tests to detect infections with the deadly, exotic WNV using new strategies. Read moreRead less
The cellular basis of sex-specific responses to virus infection. This project aims to explore how the sex of cells impacts virus infections in culture. To date, the sex of cells in culture has been overlooked as an important source of biological variability, but may be found to affect basic science through to anti-viral drug discovery. Using a model in which a virus can be adapted to grow better in cells of a single sex, this project expects to generate new knowledge about how sex differences im ....The cellular basis of sex-specific responses to virus infection. This project aims to explore how the sex of cells impacts virus infections in culture. To date, the sex of cells in culture has been overlooked as an important source of biological variability, but may be found to affect basic science through to anti-viral drug discovery. Using a model in which a virus can be adapted to grow better in cells of a single sex, this project expects to generate new knowledge about how sex differences impact virus-host interactions. This project expects to provide new insights into sex-based differences in how cells detect and respond to virus infection, and the extent to which the sex of cells impacts viruses in general.Read moreRead less
Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight i ....Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight into CTL generation by providing greater understanding of how multicellular systems function both at the cellular and molecular level.Read moreRead less
Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur betwee ....Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur between cells of the immune system during infectious diseases. The insight provided by this project will facilitate the design of better vaccines for protection against diseases, including influenza.Read moreRead less
Mechanisms of infertility induced in mice by vaccination with murine zona pellucida 3. This research investigates the means by which a novel immunocontraceptive vaccine induces an infertile state in female mice. The vaccine stimulates an autoimmune condition which resembles certain naturally occurring ovarian diseases. By investigating how ovarian cellular interactions are maintained in normal ovaries and disrupted by the immunocontraceptive vaccine, we will learn a great deal about ovarian fu ....Mechanisms of infertility induced in mice by vaccination with murine zona pellucida 3. This research investigates the means by which a novel immunocontraceptive vaccine induces an infertile state in female mice. The vaccine stimulates an autoimmune condition which resembles certain naturally occurring ovarian diseases. By investigating how ovarian cellular interactions are maintained in normal ovaries and disrupted by the immunocontraceptive vaccine, we will learn a great deal about ovarian function in health and disease. Ultimately this information will be applied to improving the reproductive health of women.
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Microcrystallography of spheroids: crystalline armours of insect viruses. The proposed project will provide fundamental insights into the organisation of ultra-stable armours protecting insect viruses. This will open novel avenues for the development of highly efficient and specific bioinsectides as well as innovative tools such as natural microparticles for improved vaccines.
The techniques used in this project are at the frontier of imaging techniques and will establish a national expertise i ....Microcrystallography of spheroids: crystalline armours of insect viruses. The proposed project will provide fundamental insights into the organisation of ultra-stable armours protecting insect viruses. This will open novel avenues for the development of highly efficient and specific bioinsectides as well as innovative tools such as natural microparticles for improved vaccines.
The techniques used in this project are at the frontier of imaging techniques and will establish a national expertise in X-ray micro-crystallography. This will contribute to the optimal use of the $8-million microfocus beamline of the newly built Australian Synchrotron enabling breakthroughs such as the structures of membrane receptors for hormone and neurotransmitter with major implications for drug development.Read moreRead less
Hyperactive endogenous retroviruses and their impact on the koala genome. Koala populations are in steep decline with the ubiquitous koala retrovirus (KoRV) strongly linked with disease. KoRV and other less studied endogenous retrovirus (ERVs) are extremely active within the genome of koalas to a level never observed in any other vertebrate genome. This study will map ERV integration sites within koalas from across their geographic range country and use long-read genomics approaches to understan ....Hyperactive endogenous retroviruses and their impact on the koala genome. Koala populations are in steep decline with the ubiquitous koala retrovirus (KoRV) strongly linked with disease. KoRV and other less studied endogenous retrovirus (ERVs) are extremely active within the genome of koalas to a level never observed in any other vertebrate genome. This study will map ERV integration sites within koalas from across their geographic range country and use long-read genomics approaches to understand the link between KoRV and other ERVs, the impact on koala caused by dramatic genomic rewiring, and the mechanisms of genomic immunity which supress ERV activity and mitigate disease. Findings will provide insights into the ongoing arms race between virus and host and inform conservation of an iconic species.Read moreRead less
Understanding the mechanism of Wolbachia-mediated antiviral protection. Insects are involved in the transmission of many viral diseases of both plants and animals. A considerable number of these diseases have adverse effects for public health or cause large economic losses in agriculture. We were the first to discover that a common bacteria protects insects from virus infection. Knowledge of the mechanisms used by the bacteria to interfere with virus accumulation will facilitate novel strategies ....Understanding the mechanism of Wolbachia-mediated antiviral protection. Insects are involved in the transmission of many viral diseases of both plants and animals. A considerable number of these diseases have adverse effects for public health or cause large economic losses in agriculture. We were the first to discover that a common bacteria protects insects from virus infection. Knowledge of the mechanisms used by the bacteria to interfere with virus accumulation will facilitate novel strategies for control of virus disease. The findings of this project will enable Australian researchers and industry to design innovative approaches to control diseases that are transmitted by insects.Read moreRead less