Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and dete ....Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and determine the architecture of several chromatin states with unique functional implications inside the cell. This will unravel the molecular instructions that define how our genomes are organised, significantly advancing our knowledge of fundamental eukaryotic genome biology and paving the way for the future development of new tools and therapies.Read moreRead less
Transport of nucleotide sugars and their roles in cell wall biosynthesis. This project aims to define and manipulate transporters involved in the delivery of activated sugars for cell wall polymer biosynthesis. Cell wall polymers play important structural and functional roles in plants. They also represent an important renewable resource in the form of biomass and contribute to the nutritional value of food. The project will complete the characterisation of cell wall-associated transporters, app ....Transport of nucleotide sugars and their roles in cell wall biosynthesis. This project aims to define and manipulate transporters involved in the delivery of activated sugars for cell wall polymer biosynthesis. Cell wall polymers play important structural and functional roles in plants. They also represent an important renewable resource in the form of biomass and contribute to the nutritional value of food. The project will complete the characterisation of cell wall-associated transporters, apply new technologies to visualise cell wall biosynthesis in growing plants and leverage this knowledge to manipulate biomass in rice. This information will provide fundamental knowledge on a crucial process in plants that can be used the development of functional foods for agriculture and tailored biomass for industry.Read moreRead less
Iron accumulation in the nematode C.elegans: a model of ageing. This project will investigate the role of biological metals in the process of ageing, the causes of which remain unresolved. The practical outcomes for society are broad; beyond improving understandings of the basic biology of ageing, this study will provide new insight and approaches that can be used to optimise lifespan.
The LINK to Regulating Lysine Levels in Wheat. This project aims to characterise a recently discovered allosteric mechanism called 'Ligand-Induced association by Lysine (K)' (LINK) model. LINK model regulates the function of a key biosynthetic enzyme in bacteria and plants, including agriculturally-important species such as wheat. Also, it represents a highly significant discovery to the field of biochemistry. The expected outcomes of this project include an in-depth understanding of the molecul ....The LINK to Regulating Lysine Levels in Wheat. This project aims to characterise a recently discovered allosteric mechanism called 'Ligand-Induced association by Lysine (K)' (LINK) model. LINK model regulates the function of a key biosynthetic enzyme in bacteria and plants, including agriculturally-important species such as wheat. Also, it represents a highly significant discovery to the field of biochemistry. The expected outcomes of this project include an in-depth understanding of the molecular basis of a new allosteric mechanism for regulating intracellular lysine levels, which in the longer term offers excellent potential to be manipulated for agricultural benefits.Read moreRead less
Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid ....Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid separation, identification and quantification of isomeric lipids. These next generation technologies will be deployed in the hope of unmasking the molecular diversity within the lipidomes of two important mammalian cell types, thus providing fundamental new insights into the structure and function of lipids within living systems.Read moreRead less
Bioinorganic chemistry between immune cell and pathogen. This project aims to investigate the bioinorganic chemistry that occurs when immune system cells encounter pathogens and they try to kill one another, or in the case of a pathogen, to also modify the genetics of the mammalian cell to enable its intracellular survival. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes and it was recently discovered that Cr is likely to be an important virulence factor. Similarly, H ....Bioinorganic chemistry between immune cell and pathogen. This project aims to investigate the bioinorganic chemistry that occurs when immune system cells encounter pathogens and they try to kill one another, or in the case of a pathogen, to also modify the genetics of the mammalian cell to enable its intracellular survival. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes and it was recently discovered that Cr is likely to be an important virulence factor. Similarly, Hyperaccummulation of Nickel (Ni) is also involved in virulence. The project will investigate the roles of Cr and Ni in virulence using advanced spectroscopic imaging and biochemical techniques. These insights will provide new knowledge on the innate immune system and may lead to more efficacious treatments for serious infections.Read moreRead less
Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is call ....Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is called Senile Systemic Amyloidosis (SSA). It is not known how or why this happens. There is no cure or therapy. This project will use transthyretins from human and wallaby to explore a possible cause of SSA. If our hypothesis is correct, we will propose preventative actions to reduce the incidence of SSA in the future.Read moreRead less
Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be ch ....Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be characterised in-field at the site(s) of infection outbreaks. This rapid response is vital, particularly in the event of a pandemic or a deliberate release of the virus in a bioterrorist attack.Read moreRead less
Deciphering the cellular defences against aggregating proteins in human disease. Cells have inbuilt defences for coping with proteins that bend into abnormal sticky shapes that form toxic clusters. In many diseases, including Huntington's, the clusters severely damage nerve cells. This project will identify the genes and mechanisms cells use to protect themselves from toxic clusters, which could provide new therapeutic targets.
The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to c ....The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to clinical observations regarding dietary intake of selenium and other compounds. The new understanding generated will delineate the conditions for safe intake, so that the beneficial effects associated with selenium supplementation may be harnessed more effectively.Read moreRead less