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Molecular Basis For The Efficient Processing Of Antigens Taken Up By Clec9A, A DAMP Receptor On Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,302,392.00
Summary
Dendritic cells (DC) of the immune system utilise specific receptors to sense danger signals from their environment. We identified a DC danger receptor, Clec9A, which recognizes and induces immunity to “dangerous” dead cells eg. infected cells or killed tumour cells. We will investigate how DC use Clec9A to process “dangerous” dead cells, and the factors that control the potency of this immune response. This will enable us to develop novel immunotherapies for infectious diseases and cancer.
Molecular Characterisation Of The Dendritic Cell Receptor Clec9a And Its Ligand Interactions
Funder
National Health and Medical Research Council
Funding Amount
$651,784.00
Summary
The immune system senses danger from infectious diseases, damaged and dead cells. We identified a danger receptor, Clec9A, on a specialised cell type of the immune system in mice and humans. Clec9A recognizes and induces immunity to dangerous dead cells. Delivering vaccines to Clec9A improves vaccine responses. We will investigate how Clec9A recognises and reacts to danger, and how we can mimic this recognition to improve vaccine design.
Colorectal cancer is a leading cause of cancer-related deaths worldwide. Chronic inflammation is recognized as a predisposing factor for the development of colon cancer, but the molecular mechanisms linking inflammation and tumourigenesis have remained elusive. Our work will dissect the cellular and molecular circuitry that leads to tumourigenesis and investigate interventions aimed to significantly slow or prevent tumour formation. This work will have significant implications for treatments of ....Colorectal cancer is a leading cause of cancer-related deaths worldwide. Chronic inflammation is recognized as a predisposing factor for the development of colon cancer, but the molecular mechanisms linking inflammation and tumourigenesis have remained elusive. Our work will dissect the cellular and molecular circuitry that leads to tumourigenesis and investigate interventions aimed to significantly slow or prevent tumour formation. This work will have significant implications for treatments of intestinal inflammation and colon cancer.Read moreRead less
The development of protective immunity is essential to fight infection. This depends on a small number of master regulatory transcription factors that drive the differentiation of precursor cells into mature immune cells such as NK, T and dendritic cells. This proposal will provide a fundamental advance in our understanding of immune cells and impact strategies aimed at the prevention and treatment of pathogen infections.
Co-ordinating The Intrinsic And Extrinsic Arms Of Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$615,286.00
Summary
The cell types of the blood, such as red and white blood cells, are produced in the bone marrow from a rare stem cell. The stem cell uses a handfull of important master-regulatory genes that act in a hierarchy to promote the blood cell differentiation process. This research aims to understand how these master-regulators function in isolation and together in producing the white blood cells that are required for our immune response to microbes, vaccination and to prevent cancer.
The Transcriptional Control Of The Dendritic Cell Lineages
Funder
National Health and Medical Research Council
Funding Amount
$669,872.00
Summary
The immune system can discriminate between invading microorganisms and the body's own tissues. Dendritic cells are specialised to alert the immune system in the case of infection. In this project we aim to understand how dendritic cells are generated and how they function to control the immune response. We will achieve this aim by using state of the art genomic technologies to describe the genetic programme of dendritic cells. We hope that this knowledge will enable us to better harness the immu ....The immune system can discriminate between invading microorganisms and the body's own tissues. Dendritic cells are specialised to alert the immune system in the case of infection. In this project we aim to understand how dendritic cells are generated and how they function to control the immune response. We will achieve this aim by using state of the art genomic technologies to describe the genetic programme of dendritic cells. We hope that this knowledge will enable us to better harness the immune response in situations such as vaccination.Read moreRead less
Delineating Immune Circuits For Innate And Adaptive Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
The immune system provides the essential frame-work to protect us against infection, disease and to heal tissues after trauma. This is achieved by a complex but elegant network of different types of white blood cells. Understanding the molecular wiring of these cells will provides fundamental insights to how the body fights pathogen infections and cancer and lays the foundation to therapeutic approaches to vaccination and disease treatments.
Control Of Immunoreceptor Assembly And Function By Intramembrane Sequence Elements
Funder
National Health and Medical Research Council
Funding Amount
$403,121.00
Summary
The cells of the immune system constantly survey their environment for changes that indicate damage. To sense their surroundings cells employ a host of receptors that are associated with signalling adapter proteins that initiate signalling cascades inside the cell when receptors bind ligands. This project seeks to determine the structural mechanisms of signal propagation across the plasma membrane of immune cells.
Structure And Interactions Of A Disordered Malaria Surface Protein: Implications For Antigenicity
Funder
National Health and Medical Research Council
Funding Amount
$511,020.00
Summary
Malaria is responsible for around 2 million deaths annually, many in children under 5 years of age. Merozoite surface protein 2 (MSP2) from Plasmodium falciparum is being developed as a vaccine candidate. We will investigate the structure of MSP2 in various environments, including when bound to inhibitory antibodies. Key goals are to understand how the disordered structure of MSP2 affects its interaction with the host immune system and how that information can be used to design better vaccines.
Immunoregulation, Innate And Adaptive Immunity, Viral Immunology, Ocular Immunology, Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$880,454.00
Summary
The focus on our research is to understand how the immune system responds to viral challenges and how viruses attempt to counteract immune responses. We focus on systemic disease, as well as disease that involve the eye. Understanding how immune responses are regulated will allows us to develop improved therapies