In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-ski ....In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-skilled techniques, including cryo-electron microscopy and single-molecule imaging and holds ancillary benefits to postgraduate students. Anticipated outcomes include influential publications, building a critical mass of expertise in Australia and fostering international collaborations with Australia at the epicentre.Read moreRead less
Atomic scale ion microscopy via laser cooling and correlated imaging. This project will develop next-generation focused ion beam microscopy and nanofabrication using a novel cold ion source based on photoionisation of a laser-cooled atom beam. The low temperature and complex internal state structure of the constituent atoms combine to allow generation of ions with unprecedented brightness and resolution. We will use three unique and innovative ideas: field ionisation of atoms in so-called 'excep ....Atomic scale ion microscopy via laser cooling and correlated imaging. This project will develop next-generation focused ion beam microscopy and nanofabrication using a novel cold ion source based on photoionisation of a laser-cooled atom beam. The low temperature and complex internal state structure of the constituent atoms combine to allow generation of ions with unprecedented brightness and resolution. We will use three unique and innovative ideas: field ionisation of atoms in so-called 'exceptional' states to reduce chromatic aberration; electron-ion correlations to enhance control of the ions at the nanoscale; and atom-atom interactions to isolate and manipulate individual ions. The new technology will enable advances in semiconductor nanofabrication and material characterisation.Read moreRead less
Experiment-numerical-virtual Generative Design for Nondeterministic Impacts. This project will establish an advanced nondeterministic design methodology to uncover the optimised material properties and 3D printed metastructural capacity in real-time against impact loading. It will develop a rigorous framework that integrates numerical simulation, experiment, and machine learning-based virtual modelling to tackle practical challenges in design and manufacture of impact-proof materials and structu ....Experiment-numerical-virtual Generative Design for Nondeterministic Impacts. This project will establish an advanced nondeterministic design methodology to uncover the optimised material properties and 3D printed metastructural capacity in real-time against impact loading. It will develop a rigorous framework that integrates numerical simulation, experiment, and machine learning-based virtual modelling to tackle practical challenges in design and manufacture of impact-proof materials and structures with intrinsic uncertainties. The generative design-calibration system unifying experimental-numerical-virtual processes will largely reduce the need for repetitive large-scale experimental tests. This project benefits civil, aerospace, automotive, and defence with competitive advantage through technological innovation.Read moreRead less
Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics. Antibiotic resistance in disease-causing bacteria is a rapidly growing problem, making the development of new antibiotics of critical importance. This project aims to develop naturally produced lectin-like protein antibiotics as novel antimicrobial agents. To achieve this, the project will produce an extensive library of these antibiotics and test them for potency and specificity. Using cutting-edge techniques, it will d ....Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics. Antibiotic resistance in disease-causing bacteria is a rapidly growing problem, making the development of new antibiotics of critical importance. This project aims to develop naturally produced lectin-like protein antibiotics as novel antimicrobial agents. To achieve this, the project will produce an extensive library of these antibiotics and test them for potency and specificity. Using cutting-edge techniques, it will determine how these antibiotics kill cells on a molecular and cellular level. It is anticipated this research will create the tools and knowledge required to exploit lectin-like protein antibiotics to fight bacterial infection, which will lead to their use in the prevention of crop and livestock losses due to disease.Read moreRead less
All in the family: understanding a new class of bacterial toxins. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. The outcomes could reveal novel mechanisms general to these proteins and ....All in the family: understanding a new class of bacterial toxins. This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. The outcomes could reveal novel mechanisms general to these proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this knowledge may guide the design of artificial protein pores that are selective for specific molecules with applications such as measuring metal ions, sugars, pesticides or pollutants. Read moreRead less
The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to ....The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to understand how MPEG1 interacts with the interferon signalling pathway. These data will provide fundamental insight into how perforin-like proteins are controlled and will broadly inform new approaches to modify immune function and molecular signalling events.Read moreRead less
Design Optimisation and Advanced Manufacturing of Structural Connections. This project aims to establish a new approach to designing and fabricating complex connections in spatial structures by taking advantage of latest technologies in topological optimisation and additive manufacturing. The project intends to develop new optimisation algorithms considering special constraints of additive manufacturing and to determine a cost-effective process for fabricating large metal connections. Expected o ....Design Optimisation and Advanced Manufacturing of Structural Connections. This project aims to establish a new approach to designing and fabricating complex connections in spatial structures by taking advantage of latest technologies in topological optimisation and additive manufacturing. The project intends to develop new optimisation algorithms considering special constraints of additive manufacturing and to determine a cost-effective process for fabricating large metal connections. Expected outcomes of the project include a new methodology and an advanced digital design tool, validated by experiments, for designing and fabricating efficient structural components. This should provide significant benefits to the construction industry in terms of performance enhancement, weight reduction and waste minimisation.Read moreRead less
Mechanism of secretion of large clostridial toxins . This project aims to investigate how the large clostridial toxins are secreted from important animal bacterial pathogens. This project expects to generate new knowledge about how bacteria interact with hosts through protein secretion, using a collaborative and interdisciplinary approach and cutting-edge techniques. Expected outcomes of this project include building a deep understanding of the role of export machinery in toxin secretion from ba ....Mechanism of secretion of large clostridial toxins . This project aims to investigate how the large clostridial toxins are secreted from important animal bacterial pathogens. This project expects to generate new knowledge about how bacteria interact with hosts through protein secretion, using a collaborative and interdisciplinary approach and cutting-edge techniques. Expected outcomes of this project include building a deep understanding of the role of export machinery in toxin secretion from bacteria, and the identification of new systems by which this is achieved. This should provide significant benefits, such as gaining new insights into new bacterial protein export mechanisms, with the aim of identifying targets for future veterinary disease interventions or biotechnological applications.Read moreRead less
Topological Design of Mechanical Meta-Structures. This project aims to establish a new computational design methodology to address current challenges facing creation of ultralight structures with ultra-high-performance characteristics. The latest technologies in structural topology optimization and its correlated numerical simulation and structural analysis methods will be unified towards an integrated design framework. Expected outcomes include an advanced generative design platform for discove ....Topological Design of Mechanical Meta-Structures. This project aims to establish a new computational design methodology to address current challenges facing creation of ultralight structures with ultra-high-performance characteristics. The latest technologies in structural topology optimization and its correlated numerical simulation and structural analysis methods will be unified towards an integrated design framework. Expected outcomes include an advanced generative design platform for discovering novel geometries to underpin new meta-structure architectures, validated by appropriate fabrication techniques considering their geometric complexity. Such capabilities will benefit defence, civil, aerospace, energy and transport industries that pursue competitive advantage through innovation.Read moreRead less
Pore-forming toxins: more than one way to make a hole. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. This project aims to unravel missing molecular details of how a major superfamily of such proteins is able to drill holes in cell membranes. The outcomes could reveal novel mechanisms general to these proteins and provid ....Pore-forming toxins: more than one way to make a hole. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. This project aims to unravel missing molecular details of how a major superfamily of such proteins is able to drill holes in cell membranes. The outcomes could reveal novel mechanisms general to these proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this knowledge may guide the design of artificial protein pores that are selective for specific molecules with applications such as measuring metal ions, sugars, pesticides or pollutants.
Read moreRead less