A structural investigation into T cell signalling machines. The project aims to understand how receptor recognition events cause intracellular signalling.Membrane-bound receptors, their cognate ligands and the ensuing intracellular activation signal determine cellular fate. The project will explore events central to cellular immunity by examining the T cell signalling machinery. This project will use labelling, crystallographic and cryo-electron microscopy studies, to determine the molecular arc ....A structural investigation into T cell signalling machines. The project aims to understand how receptor recognition events cause intracellular signalling.Membrane-bound receptors, their cognate ligands and the ensuing intracellular activation signal determine cellular fate. The project will explore events central to cellular immunity by examining the T cell signalling machinery. This project will use labelling, crystallographic and cryo-electron microscopy studies, to determine the molecular architecture of the T cell receptor (TCR) CD3 complex, a molecular machine central to T cell signalling. This project should reveal how antigen recognition leads to T cell signal transduction which will create jobs, bring substantial health benefits and improve quality of life for Australians.Read moreRead less
A structural and molecular investigation into the basic mechanism of T cell receptor complex function. Cellular fate is determined by interactions between membrane-bound receptors and their cognate ligands. The basic mechanism of how such receptor-mediated recognition events cause intracellular signalling is poorly understood in most biological systems, including the cellular immune recognition axis. This project will explore events central to cellular immunity by examining the interactions cent ....A structural and molecular investigation into the basic mechanism of T cell receptor complex function. Cellular fate is determined by interactions between membrane-bound receptors and their cognate ligands. The basic mechanism of how such receptor-mediated recognition events cause intracellular signalling is poorly understood in most biological systems, including the cellular immune recognition axis. This project will explore events central to cellular immunity by examining the interactions centred on T-cell receptor complexes. This project will explore the molecular mechanisms underpinning these key receptor-recognition events and relate these observations to T-cell activation. The proposal will shed fundamental insight into Major Histocompatibility Complex restriction, T-cell development and how antigen recognition leads to T-cell signal transduction. 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.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100179
Funder
Australian Research Council
Funding Amount
$3,189,000.00
Summary
Automated high resolution and high contrast cryo -TEM for three-dimensional structural biology. This project aims to establish a facility in automated, single-particle cryo-TEM and cryo-TEM tomography (Titan Krios) that will enable atomic and molecular structure research and three-dimensional subcellular and cellular imaging. The project will span all multiscale cryo-TEM modalities from the visualisation of cells, membranes and macromolecular complexes, through to near-atomic-resolution protein ....Automated high resolution and high contrast cryo -TEM for three-dimensional structural biology. This project aims to establish a facility in automated, single-particle cryo-TEM and cryo-TEM tomography (Titan Krios) that will enable atomic and molecular structure research and three-dimensional subcellular and cellular imaging. The project will span all multiscale cryo-TEM modalities from the visualisation of cells, membranes and macromolecular complexes, through to near-atomic-resolution protein structure determination. Cryo-single particle analysis and tomography are recognised as revolutionary technologies in molecular structural biology and powerful enablers of future ground-breaking discovery. The project will deliver significant competitive advantage for Australia in leading-edge structure-based research, drug discovery, new opportunities for applied research and development, and showcasing science to the public.Read moreRead less
A structural and functional investigation into events within the immunological synapse. This project will provide fundamental insight into processes that control infection. Investigating processes central to immunity is important, as it will further the understanding of these critically-important events. Such knowledge will increase Australia's research standing, as well as having the potential to generate novel therapies
Advanced cryobanking for propagation-recalcitrant and critically endangered plant species. This project aims to advance methods for the conservation of recalcitrant/threatened plant species to achieve best practice ecological restoration in areas of high biodiversity. In particular, the nature of freezing and dehydration damage to cell membranes at various stages of tissue culture and cryopreservation will be investigated to try to minimise deleterious effects. In addition, metabolic changes tha ....Advanced cryobanking for propagation-recalcitrant and critically endangered plant species. This project aims to advance methods for the conservation of recalcitrant/threatened plant species to achieve best practice ecological restoration in areas of high biodiversity. In particular, the nature of freezing and dehydration damage to cell membranes at various stages of tissue culture and cryopreservation will be investigated to try to minimise deleterious effects. In addition, metabolic changes that affect cryogenic survival will be assessed to provide further insight into the role of oxidative stress and the toxicity of cryopreservation processes. Ultimately, improved cryogenic protocols will be developed to maintain the integrity of long-term cryobanks of key species for ecological restoration, such as in post-mined areas.Read moreRead less
Advanced cryobanking for recalcitrant-seeded Australian rainforest plants. This project aims to develop an interdisciplinary research alliance to enhance the efficiency of ecological restoration for recalcitrant Australian rainforest plant species. The project expects to provide fundamental knowledge to target two major impediments to cryostorage of recalcitrant-seeded native species: desiccation sensitivity with relatively large size, and active metabolism and precocious germination. These attr ....Advanced cryobanking for recalcitrant-seeded Australian rainforest plants. This project aims to develop an interdisciplinary research alliance to enhance the efficiency of ecological restoration for recalcitrant Australian rainforest plant species. The project expects to provide fundamental knowledge to target two major impediments to cryostorage of recalcitrant-seeded native species: desiccation sensitivity with relatively large size, and active metabolism and precocious germination. These attributes severely limit the time available for effective use of collected germplasm for long-term storage. A combination of biochemical, biophysical and molecular simulation approaches will be used to optimise cryopreservation of a wide range of endangered Australian rainforest species. This should provide significant benefits such as enabling conservation agencies to greatly enhance their ability to preserve the unique Australian rainforest flora, particularly given current threats due to habitat loss and global warming.Read moreRead less
ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the d ....ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the design of peptides and proteins for targeted scientific, agricultural, biotechnology, animal health and pharmaceutical applications. CIPPS will assemble leading researchers from diverse disciplines to create a sustainable national entity that will drive new Australian industries and train next generation researchers.Read moreRead less
Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the desig ....Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the design of future biological nano-motors. Our work will provide an understanding of the regulation of this enzyme with potential application in the control of nano-motors.Read moreRead less