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Beyond structure - solving conformational dynamics for intractable proteins. Proteins perform almost every task that enables the amazing complexity of cellular and whole organism physiology. These molecular machines perform this incredible array of tasks due to their ability to dynamically change shape. For the vast majority of these machines, we can only view a snapshot of the possible shapes they can adopt and can’t monitor how they change from one shape to another, which is critical for their ....Beyond structure - solving conformational dynamics for intractable proteins. Proteins perform almost every task that enables the amazing complexity of cellular and whole organism physiology. These molecular machines perform this incredible array of tasks due to their ability to dynamically change shape. For the vast majority of these machines, we can only view a snapshot of the possible shapes they can adopt and can’t monitor how they change from one shape to another, which is critical for their functioning. This project aims to develop and apply a completely new method to visualise dynamic changes in protein shape which is not possible with current techniques. This will allow us to provide a new description and understanding of the function of proteins, which is fundamental to all biology.Read moreRead less
A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevale ....A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevalent in immune responses, and all recognise pMHCI using a conserved orientation. This project aims to use this observation to study the relationship between TCR recognition modes and T cell recruitment and activation.Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
Molecular toxinology of Australia's lesser known venomous snakes. This proposal represents a tremendous opportunity for biodiscovery from venomous snakes. This will be achieved through the researchers' unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate stude ....Molecular toxinology of Australia's lesser known venomous snakes. This proposal represents a tremendous opportunity for biodiscovery from venomous snakes. This will be achieved through the researchers' unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate students with finely tuned skills in cutting edge methodological techniques and a fluent understanding of molecular evolution, preparing them to be internationally competitive scientists.Read moreRead less
Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enz ....Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enzymes regulated by fat molecules that will be of great interest to researchers across many branches of life sciences. Expected outcomes and benefits will be deeper understanding of fat molecules as nutrient signalling metabolites, and how they influence cell metabolism, growth and development.Read moreRead less
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less
Molecular control of postnatal heart development. This project aims to improve our understanding of how the heart develops after birth and the molecules that control this process. Recent advances in tissue engineering have opened up opportunities for the generation of synthetic tissues but these studies have also highlighted a fundamental knowledge gap in our understanding of how complex tissues mature to prepare for life as an adult. Much is known about the molecules that control early embryoni ....Molecular control of postnatal heart development. This project aims to improve our understanding of how the heart develops after birth and the molecules that control this process. Recent advances in tissue engineering have opened up opportunities for the generation of synthetic tissues but these studies have also highlighted a fundamental knowledge gap in our understanding of how complex tissues mature to prepare for life as an adult. Much is known about the molecules that control early embryonic development but little is known about the molecules that control maturation after birth. This project aims to build new knowledge that is expected to improve our ability to generate mature heart muscle cells for stem cell applications, tissue repair and regeneration.Read moreRead less
Functional analysis of alternative splicing in plants. Higher temperatures affect flowering and seed set in plants. How plants sense and respond to temperature is currently unclear. Here we study alternative splicing, one of the processes affected by temperature. These studies will advance our knowledge and help develop crops that can withstand negative effects of climate change.
Is SPINT1 a key regulator of placental development? . The placenta is an essential organ required for reproduction in placental species. This project aims to elucidate the fundamental biology of SPINT1 in placental development. It will generate new knowledge about whether the spatial and temporal expression of SPINT1 is conserved across several species; cow, sheep, lizard, mouse and human. It will also define the molecular mechanisms by which SPINT1 directs formation, maturation and expansion o ....Is SPINT1 a key regulator of placental development? . The placenta is an essential organ required for reproduction in placental species. This project aims to elucidate the fundamental biology of SPINT1 in placental development. It will generate new knowledge about whether the spatial and temporal expression of SPINT1 is conserved across several species; cow, sheep, lizard, mouse and human. It will also define the molecular mechanisms by which SPINT1 directs formation, maturation and expansion of the placental exchange interface which is critical for offspring survival.
The project will increase understanding of placental development, enhance collaboration and research knowhow, and promote future applied projects in all species that reproduce via placental support.Read moreRead less