A portable RNA-editing machine. Many plants maintain an elaborate RNA-editing machine that allows them to correct accumulated errors in their organellar genomes by specifically editing the RNA transcripts of the affected genes. A portable and adaptable version of this molecular machine would have significant biotechnological value, providing the ability to correct genetic errors, and to intervene in gene regulation without permanently altering a genome. The project aims to combine molecular and ....A portable RNA-editing machine. Many plants maintain an elaborate RNA-editing machine that allows them to correct accumulated errors in their organellar genomes by specifically editing the RNA transcripts of the affected genes. A portable and adaptable version of this molecular machine would have significant biotechnological value, providing the ability to correct genetic errors, and to intervene in gene regulation without permanently altering a genome. The project aims to combine molecular and structural biology approaches to fully characterise the components of the machine, thus allowing us to reconstitute it in cell-free systems and ultimately in other organisms.Read moreRead less
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
Mastering pyrimidine editing in RNA. Many plants and animals can alter their genetic information via RNA (ribonucleic acid) editing, a process that is often essential for the growth and development of the organism. This ability provides accurate control over gene expression and has great potential as a biotechnological tool in agriculture and medicine. RNA editing could be used to switch genes on or off in biotechnological production systems with an unprecedented degree of precision, or to corre ....Mastering pyrimidine editing in RNA. Many plants and animals can alter their genetic information via RNA (ribonucleic acid) editing, a process that is often essential for the growth and development of the organism. This ability provides accurate control over gene expression and has great potential as a biotechnological tool in agriculture and medicine. RNA editing could be used to switch genes on or off in biotechnological production systems with an unprecedented degree of precision, or to correct genetic diseases. This project aims to understand two RNA editing pathways in plants, one of which is found nowhere else and likely to involve a novel enzymatic mechanism. We will use the understanding gained to develop novel RNA processing tools usable in any living organism.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101210
Funder
Australian Research Council
Funding Amount
$375,837.00
Summary
A liquid protein platform for dynamic bio-inspired reaction compartments. This project aims to investigate liquid protein as a novel material for biotechnology by producing protein droplets with a range of material and structural properties and assess the activity of internalised enzymes. The project will combine concepts from protein-based subcellular super-structure and enzyme protein structure and apply cutting-edge biochemistry methods to study how catalysis can be controlled and directed th ....A liquid protein platform for dynamic bio-inspired reaction compartments. This project aims to investigate liquid protein as a novel material for biotechnology by producing protein droplets with a range of material and structural properties and assess the activity of internalised enzymes. The project will combine concepts from protein-based subcellular super-structure and enzyme protein structure and apply cutting-edge biochemistry methods to study how catalysis can be controlled and directed through liquid protein design. Expected outcomes include a new platform for using protein droplets to engineer dynamic catalytic compartments, strong international and interdisciplinary collaborations, and a knowledge-base for building synthetic biology tools and technologies for future green chemistry-based industries.Read moreRead less
Engineering self-assembled intracellular biological condensates. Cells depend on proteins linking together to build cellular structure, but how weak interactions build stable structure is a mystery. New evidence suggests proteins come together and then change state, employing liquid-like behaviour that builds vital nanoscale structure, such as nuclear bodies called paraspeckles. This project will unlock the secrets of this mysterious behavior of proteins, using paraspeckles as a model. We will u ....Engineering self-assembled intracellular biological condensates. Cells depend on proteins linking together to build cellular structure, but how weak interactions build stable structure is a mystery. New evidence suggests proteins come together and then change state, employing liquid-like behaviour that builds vital nanoscale structure, such as nuclear bodies called paraspeckles. This project will unlock the secrets of this mysterious behavior of proteins, using paraspeckles as a model. We will use this information for nanotechnology application to build a synthetic paraspeckle inspired structure with bespoke function. Benefits will include new concepts in how vital cell structure is assembled and disassembled, and nanotechnology and synthetic biology tools to manipulate cellular processes.Read moreRead less
The structure in four-dimensions of a mammalian nuclear body. The project aims to develop a working model of a micron-sized molecular machine implicated in numerous aspects of gene regulation. Bodies in the mammalian cell nucleus are larger than macromolecular complexes and smaller than organelles. Recent developments in structural, molecular and cell biology are allowing us to begin to interpret their structure-function relationships. This project capitalises on a wealth of structural and funct ....The structure in four-dimensions of a mammalian nuclear body. The project aims to develop a working model of a micron-sized molecular machine implicated in numerous aspects of gene regulation. Bodies in the mammalian cell nucleus are larger than macromolecular complexes and smaller than organelles. Recent developments in structural, molecular and cell biology are allowing us to begin to interpret their structure-function relationships. This project capitalises on a wealth of structural and functional data on nuclear bodies termed paraspeckles with the aim of developing a structural model. It aims to track tens of proteins and long non-coding RNA from paraspeckles as they proceed through the cell cycle, by combining genome engineering, super-resolution microscopy, proteomics and in vitro interaction studies.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