Investigating gamma/delta T cell receptor recognition determinants. The immune system has evolved to protect hosts from pathogens. T cells are a critical component of the immune system that can recognise infected host cells. However, there remains many facets of T cell function that we do not understand. This project aims to investigate a major aspect of T cell immunity that is poorly understood, namely, gamma/delta T cell immunity. Specifically, using a multi-disciplinary approach, the anticip ....Investigating gamma/delta T cell receptor recognition determinants. The immune system has evolved to protect hosts from pathogens. T cells are a critical component of the immune system that can recognise infected host cells. However, there remains many facets of T cell function that we do not understand. This project aims to investigate a major aspect of T cell immunity that is poorly understood, namely, gamma/delta T cell immunity. Specifically, using a multi-disciplinary approach, the anticipated outcome of the project is to unearth the molecular recognition determinants of gamma/delta T cells. The intended outcome is to provide basic fundamental insights and conceptual advances into a poorly understood, but crucial, component of the immune system. Read moreRead less
Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodellin ....Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodelling is organised at a cell-type level is not understood. Here we aim to close this knowledge gap, using cutting-edge technology including bioconjugation and ultrasound-mediated cargo delivery. Together, this project aims to contribute to a deeper understanding of this major brain compartment in neuronal function. Read moreRead less
A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Person ....A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Personnel will be trained in cutting-edge techniques. The project will expand knowledge on basic immunology and cell-cell cooperation. It will generate intellectual property for the biotechnology sector to develop new commercial products that might improve the health of humans and also animals of economic importance.Read moreRead less
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
Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SF ....Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SFV greatly perturbs T cell dynamics. This proposal will study, at cellular and molecular levels, T cell trafficking, function and clonal distribution during antigenic interference, thus advance fundamental knowledge on T cell immunity during antigenic competition, and provide a new paradigm on how we research T cell immunity.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101012
Funder
Australian Research Council
Funding Amount
$470,789.00
Summary
Redefining how T cell recognition drives T cell activation. This proposal aims to define the key mechanisms that determine how T cells recognise and respond to foreign antigens; a critical feature that defines effective immunity. To achieve this goal, this proposal will leverage multidisciplinary collaborations and innovative methods to understand how structural and biochemical features of T cell receptor recognition influences T cell mediated immunity and development. In turn, this project will ....Redefining how T cell recognition drives T cell activation. This proposal aims to define the key mechanisms that determine how T cells recognise and respond to foreign antigens; a critical feature that defines effective immunity. To achieve this goal, this proposal will leverage multidisciplinary collaborations and innovative methods to understand how structural and biochemical features of T cell receptor recognition influences T cell mediated immunity and development. In turn, this project will facilitate further research and development in the burgeoning field of T cell biology and advance life science research in Australia. Furthermore, as T cell biology is relevant to all vertebrates, this research will greatly benefit the conservation of threatened animal species and agriculture.Read moreRead less
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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Adrenomedullin: a specific regulator of venous vessel integrity. Arteries and veins display different adhesive properties, which enable them to fulfil their physiological roles. We are yet to understand the mechanisms that establish and maintain adhesive function in different vessel types. We have discovered that signalling by the peptide Adrenomedullin (ADM) is a key mediator of adhesion, only in veins but not arteries. This project aims to utilise innovative models (zebrafish, mouse and bioeng ....Adrenomedullin: a specific regulator of venous vessel integrity. Arteries and veins display different adhesive properties, which enable them to fulfil their physiological roles. We are yet to understand the mechanisms that establish and maintain adhesive function in different vessel types. We have discovered that signalling by the peptide Adrenomedullin (ADM) is a key mediator of adhesion, only in veins but not arteries. This project aims to utilise innovative models (zebrafish, mouse and bioengineered vessels) to identify the biochemical and mechanical mechanisms by which ADM controls venous adhesion. Outcomes will improve our understanding on how vessel integrity is controlled across vessel types and will expand the scope of Australian research by informing efforts to vascularise engineered tissues.Read moreRead less
An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the r ....An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the responding T cells. This basic science discovery project will provide substantial new knowledge in the burgeoning field of lipid-mediated immunity, which should ultimately lead to new therapies targeting the CD1a lipid display molecule to either prevent immune mediated damage or promote protective immunity as required.Read moreRead less