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Antigen Selection In The MHC-restricted Cellular Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$175,570.00
Summary
The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally appare ....The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally apparent when molecules called antigens are released by microorganisms and captured by the body's cells. This activates lymphocytes resulting in an immune response capable of eliminating the microorganisms. Scrutiny of the body's cells by lymphocytes occurs continuously even when there is no infection present in the body. Following infection of a cell, microbial antigens reveal the infection by their appearance on the cell surface where they are detected by the immune system's lymphocytes. This occurs through a mechanism called antigen presentation. During antigen presentation the proteins inside the cell, including those of any invading microorganism, are first degraded into shorter molecules called peptides. This event is called antigen processing. A fraction of the peptides created by antigen processing are captured by specialised receptors present on all cells. These receptors are called HLA or histocompatibility molecules. This project examines the molecular events which mediate the capture of peptide antigens by HLA molecules. The main focus is on those peptide antigens which elicit killer T cell responses by the immune system. A knowledge of how these peptides are selected for presentation and how they are captured and carried to the cell surface is fundamental to understanding immune responses to microorganisms, tumours, allergens, transplants and self tissues as in autoimmunity. Therefore the study is of great general relevance.Read moreRead less
Compartmental Analysis Of T-cell Responses In Thoracic Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$851,403.00
Summary
To improve immune therapy for cancer we have to be able to determine how cancer patients ‘see’ mutated cancer proteins. Blood is the easiest & most useful source of immune ‘killer’ cells for that task, but the lymph node that drains the tumour and the fluid that bathes a tumour probably contain a much higher number of these killer cells than blood. If so, studying them would help us better track responses to therapy and enable us to choose the best mutated proteins for a vaccine.
Feeding and digestion in tropical rock lobster phyllosoma larvae and its applications for culture. Provision of larval culture diets that provide optimal nutrition in a suitable presentation format is the major challenge for developing a rock lobster aquaculture industry. Tropical rock lobsters are likely contenders due to their faster growth rates and shorter larval phase than temperate species. This project will assess the ingestive and digestive capabilities of larvae during development, thro ....Feeding and digestion in tropical rock lobster phyllosoma larvae and its applications for culture. Provision of larval culture diets that provide optimal nutrition in a suitable presentation format is the major challenge for developing a rock lobster aquaculture industry. Tropical rock lobsters are likely contenders due to their faster growth rates and shorter larval phase than temperate species. This project will assess the ingestive and digestive capabilities of larvae during development, through an examination of mouthpart and gut structure and their types and concentration of digestive enzymes. Information will be used to formulate and test improved diets of appropriate size, texture and nutritional composition and will be the first comprehensive analysis of preferred larval diets on the basis of their biological and physiological characteristics.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
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
IDENTIFYING CONTROL ELEMENTS IN CHLOROPLAST GENE EXPRESSION. Energy from sunlight is captured by photosynthesis in plants, providing the basis for the terrestrial food chain. This process takes place in chloroplasts, subcellular structures that derived from photosynthetic bacteria a billion years ago. Chloroplasts have their own DNA, containing genes encoding the most important photosynthetic proteins. This project aims to provide the world’s best resources for the study of chloroplast genes. In ....IDENTIFYING CONTROL ELEMENTS IN CHLOROPLAST GENE EXPRESSION. Energy from sunlight is captured by photosynthesis in plants, providing the basis for the terrestrial food chain. This process takes place in chloroplasts, subcellular structures that derived from photosynthetic bacteria a billion years ago. Chloroplasts have their own DNA, containing genes encoding the most important photosynthetic proteins. This project aims to provide the world’s best resources for the study of chloroplast genes. In the process, we will discover how these important genes are regulated to provide photosynthetic proteins in the right amounts, in the right cells, at the right time. The knowledge and resources gained will facilitate improvement of photosynthetic function in future agricultural crops.Read moreRead less
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