Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds ....Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds of fusion. This recycling process ensures that neurons communicate efficiently, however the underpinning mechanism is unknown. This project aims to use a recently developed single synaptic vesicle super-resolution tracking method to establish how Myosin-VI and Synapsin-IIa orchestrate this recycling in central and peripheral neurons. It will explain how neurons manage to preserve their ability to communicate.Read moreRead less
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
Mechanisms of itch - from endosomal signalling to neural circuits. This project aims to investigate the cellular and circuit mechanisms of itch transmission in the spinal cord by defining the activation and propagation of itch-specific signals. This project expects to generate new knowledge in the area of neuronal signalling and circuitry using novel electrophysiological approaches that target and manipulate specific nerves and cellular components. The project will characterise signalling within ....Mechanisms of itch - from endosomal signalling to neural circuits. This project aims to investigate the cellular and circuit mechanisms of itch transmission in the spinal cord by defining the activation and propagation of itch-specific signals. This project expects to generate new knowledge in the area of neuronal signalling and circuitry using novel electrophysiological approaches that target and manipulate specific nerves and cellular components. The project will characterise signalling within specific spinal subcircuits in order to understand the mechanisms of receptor activation and signalling, and investigate how circuit activity is regulated. This project expects to advance fundamental understanding of itch signalling in the nervous system and provide avenues for future therapeutics.Read moreRead less
Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new pro ....Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new processes of how normal body hormones and administered steroids may function. This may eventually lead to new and more effective ways to control inflammation that will have significant benefits to mammalian health and improve health care and agriculture outcomes.Read moreRead less
Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innov ....Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innovative genome editing, mathematical modelling and proteomic approaches, to study how biochemical modifications of a key protein called tau help encode and retrieve memories. These molecular insights will make a significant advance in the current understanding of a brain function that is essential to all human activities.Read moreRead less
Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, wh ....Molecular control of memory traces. This project aims to understand how particular molecules help encode memories in the brain for future retrieval. Individual memories are encoded in brain cells through an unknown physical process. This project uses innovative approaches to manipulate memory-containing cells and will provide a new detailed explanation of memory. Outcomes of this work will significantly advance the current understanding of how memories are physically generated and maintained, which is an essential component of human and animal life. This research provides significant benefits in understanding the biology behind memory and in maintaining memory capacity in ageing.
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Investigating the atomic structure of an immune cell inhibitory receptor. T cells play a key role in the adaptive immune system, whose reactivity must be controlled to prevent aberrant reactivity. Central to the function of T cells is the T cell antigen receptor, and a host of co-stimulatory molecules, co-receptors and inhibitory receptors. This proposal, in partnership with Immutep Ltd, aims to gain a basic understanding of the structure and function of a key inhibitory receptor found on T cel ....Investigating the atomic structure of an immune cell inhibitory receptor. T cells play a key role in the adaptive immune system, whose reactivity must be controlled to prevent aberrant reactivity. Central to the function of T cells is the T cell antigen receptor, and a host of co-stimulatory molecules, co-receptors and inhibitory receptors. This proposal, in partnership with Immutep Ltd, aims to gain a basic understanding of the structure and function of a key inhibitory receptor found on T cells, termed the Lymphocyte activation gene-3 (LAG-3). The proposal utilises a combination of cellular immunology and structural biology to gain insight into the form and function of the LAG-3 molecule. Ultimately this fundamental knowledge can be used by the biotechnology industry.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101491
Funder
Australian Research Council
Funding Amount
$443,312.00
Summary
A molecular investigation into metabolite-mediated T cell immunity. This project aims to undertake discovery research to investigate the roles of metabolites in T cell immunity. This project expects to generate new knowledge in the areas of cellular biology and immunology by using cutting-edge molecular and immunological approaches. This will provide fundamental insights into the mechanisms that govern microbial metabolite-based T cell immunity, which may advise future research into vaccines or ....A molecular investigation into metabolite-mediated T cell immunity. This project aims to undertake discovery research to investigate the roles of metabolites in T cell immunity. This project expects to generate new knowledge in the areas of cellular biology and immunology by using cutting-edge molecular and immunological approaches. This will provide fundamental insights into the mechanisms that govern microbial metabolite-based T cell immunity, which may advise future research into vaccines or therapeutics. In addition to knowledge gains, expected outcomes of this project include the development of innovative methodology and building international collaborations to enhance national research capabilities. This will place Australia at the forefront of conceptually innovative discovery in the life sciences.Read moreRead less
Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key ch ....Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key characteristic of stem cell control throughout evolution. This will increase our understanding of how energy metabolism and nutrition influence organ size control in multicellular organisms, by determining how organs communicate with each other to convert nutrient signals to action stem cell proliferation.Read moreRead less
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less