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
A Structural Investigation Into The T-cell Response To Epstein Barr Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$549,000.00
Summary
X-ray crystallography is an essential tool for solving the three-dimensional structure of proteins. Proteins control the biological processes within the cell and it is the precise shape of proteins that determines how they function. Depending on the particular sequence of the amino acids, the so-called building unit of the proteins, the protein molecule bends and forms a distinct, complex shape. This specific three-dimensional shape allows the protein to undertake its specific function, such as ....X-ray crystallography is an essential tool for solving the three-dimensional structure of proteins. Proteins control the biological processes within the cell and it is the precise shape of proteins that determines how they function. Depending on the particular sequence of the amino acids, the so-called building unit of the proteins, the protein molecule bends and forms a distinct, complex shape. This specific three-dimensional shape allows the protein to undertake its specific function, such as binding to other proteins, acting as an enzyme or interacting with nucleic acids. To determine how a protein acts, it is vital to know the precise three-dimensional shape at the atomic level. This proposal is concerned with understanding the precise shape of proteins that control the immune response to Epstein Barr Virus. Epstein Barr Virus is an ubiquitous human pathogen that has being linked to a number of cancers. This work will further our understanding of the immune response to Epstein Barr Virus.Read moreRead less
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$14,927,045.00
Summary
This program focuses on understanding the development of immunity during infection or inflammatory diseases using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune or inflammatory diseases.
A novel top-down approach to ecosystem management using multivariate foraging strategies of an iconic marine top-predator. Understanding predator aggregation patterns in relation to marine productivity is critical in designing ecosystem-level conservation plans for protecting marine habitats and species. The project aims to develop a new approach to measure prey abundance and availability in the marine ecosystem for the management of resources of top-predators. This will be of specific benefit i ....A novel top-down approach to ecosystem management using multivariate foraging strategies of an iconic marine top-predator. Understanding predator aggregation patterns in relation to marine productivity is critical in designing ecosystem-level conservation plans for protecting marine habitats and species. The project aims to develop a new approach to measure prey abundance and availability in the marine ecosystem for the management of resources of top-predators. This will be of specific benefit in areas where a strong need exists for conservation of prey species with economic importance too low to justify expensive at-sea research.Read moreRead less
Do Exposures Before Conception Influence The Risk Of Asthma In Offspring?
Funder
National Health and Medical Research Council
Funding Amount
$688,586.00
Summary
Asthma and poor lung function are major causes of public health issues. Emerging evidence suggests adverse exposures even before the conception of a child may cause these conditions. The proposed project is part of an international study across generations to identify these factors. This study will provide novel evidence to guide interventions and identify studies to advance this area further. These original findings will be of great importance both nationally and internationally.
DYRK1A As A Novel Target For Glioblastoma Therapies
Funder
National Health and Medical Research Council
Funding Amount
$620,294.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called DYRK1A (using ‘DYRK1A inhibitors’) kills glioblastoma cells. This therapeutic advantage is even greater when combined with drugs approved for other cancers. This project will develop new DYRK1A inhibitors and examine a novel combination treatment for glioblastoma patients. This could initiate a novel therapy that could significantly extend patients’ lives.
Determinant Spreading And The Role Of The MHC Class II Region In Systemic And Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$140,570.00
Summary
Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against c ....Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against components located inside cells of the body. The study involves genetically modifying mice by introducing key human genes which influence the development of autoimmunity. In this way the role of these human genes can be examined experimentally without having to work exclusively on patients. We also hope that these mice might be important in creating new models of celiac disease and insulin dependent diabetes. The proposed experiments should tell us how these genes contribute to the development of autoimmune disease. This understanding could be relevant devising treatments and interventions to prevent autoimmune diseases.Read moreRead less
Ecosystem resilience of Shark Bay under changing ocean climate. This project aims to investigate the resilience of the Shark Bay World Heritage Site to projected climate change. This project will generate new knowledge for marine conservation through analyses of habitat loss on nutrient budgets and productivity in seagrass and microbialite ecosystems. Expected outcomes are an improved understanding of climate-driven shifts on ecosystem processes in Shark Bay, incorporating science-based evidence ....Ecosystem resilience of Shark Bay under changing ocean climate. This project aims to investigate the resilience of the Shark Bay World Heritage Site to projected climate change. This project will generate new knowledge for marine conservation through analyses of habitat loss on nutrient budgets and productivity in seagrass and microbialite ecosystems. Expected outcomes are an improved understanding of climate-driven shifts on ecosystem processes in Shark Bay, incorporating science-based evidence for better conservation and management. This will provide significant benefits by contributing to the future-proofing of Shark Bay’s World Heritage values to climate change, and more broadly by demonstrating the consequences of the continued tropicalisation of Australia’s coastline.Read moreRead less
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$15,780,848.00
Summary
This program focuses on understanding the development of immune response to viruses and other infectious agents using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune diseases like diabetes.
Assessing the ecosystem-wide risks of threatened species translocation. Assessing the ecosystem-wide risks of threatened species translocation. This project aims to develop the first quantitative risk assessment framework to improve decisions about moving threatened species to new places. Moving threatened plants and animals to new environments, or reintroducing them where they previously persisted, is a growing focus of conservation. Moving species can have unanticipated effects on other specie ....Assessing the ecosystem-wide risks of threatened species translocation. Assessing the ecosystem-wide risks of threatened species translocation. This project aims to develop the first quantitative risk assessment framework to improve decisions about moving threatened species to new places. Moving threatened plants and animals to new environments, or reintroducing them where they previously persisted, is a growing focus of conservation. Moving species can have unanticipated effects on other species in the ecosystem. Although the International Union for Conservation of Nature deems ecosystem-wide risk assessments essential for conservation translocations, no framework exists to assess these risks and inform these decisions. New tools for assessing the risks of conservation translocations are expected to improve global and local conservation outcomes.Read moreRead less