Investigating the atomic structure of an immune cell inhibitory receptor. T cells play a key role in the adaptive immune system, whose reactivity must be controlled to prevent aberrant reactivity. Central to the function of T cells is the T cell antigen receptor, and a host of co-stimulatory molecules, co-receptors and inhibitory receptors. This proposal, in partnership with Immutep Ltd, aims to gain a basic understanding of the structure and function of a key inhibitory receptor found on T cel ....Investigating the atomic structure of an immune cell inhibitory receptor. T cells play a key role in the adaptive immune system, whose reactivity must be controlled to prevent aberrant reactivity. Central to the function of T cells is the T cell antigen receptor, and a host of co-stimulatory molecules, co-receptors and inhibitory receptors. This proposal, in partnership with Immutep Ltd, aims to gain a basic understanding of the structure and function of a key inhibitory receptor found on T cells, termed the Lymphocyte activation gene-3 (LAG-3). The proposal utilises a combination of cellular immunology and structural biology to gain insight into the form and function of the LAG-3 molecule. Ultimately this fundamental knowledge can be used by the biotechnology industry.Read moreRead less
microRNAs and the control of T lymphocyte differentiation, function and malignant transformation. The molecular mechanism of the immune system is not completely understood. This project will investigate how transcription factors and microRNAs, two major types of regulatory molecules work together to control immune responses. The results from this research will assist in the design of better vaccination strategies and treat certain lymphomas.
Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cell ....Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cellular imaging, this project aims to investigate the cell specific functions of these pathways and the therapeutic potential of altering their expression and function. This project may lead to the development of novel predictors of metastasis in patients and new targeted therapeutics to prevent breast cancer spread.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100106
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
An advanced flow cytometry facility for the Peter Doherty Institute. The establishment of a flow cytometry facility in the new Peter Doherty Institute for Infection and Immunity will enhance capacity to investigate immunity to a broad range of very serious diseases. This project will support researchers studying viral and bacterial infection as well as cancer and autoimmunity.
Membrane proteins in innate immunity. The application of smarter and faster methods for understanding membrane proteins, targets of most drugs, is vital to a knowledge-based economy and a healthy society. The long-term benefits will include fundamental new knowledge on immunity, and implementation of new approaches that streamline costs and efforts of challenging, high-impact research.
Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanis ....Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanisms underpinning the essential biological process of zinc homeostasis.Read moreRead less
Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell recept ....Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell receptor is determined by utilising structural biology and cellular immunology techniques. The impact of this project effects the development of innovative T cell immunomodulatory agents, improving the health and quality of life of the Australian population.Read moreRead less
Exceptions Prove the Rule: How Antigen Recognition Drives T cell Activation. CD8+ T cells are immune cells that are critical for the adaptive immune response, which is central to immune function in vertebrates. CD8+ T cells mediate their effector functions only after activation, which occurs via T cell receptor (TCR) recognition of foreign antigens. Here, unique reagents and sophisticated technologies will be used to define precisely how the nature of TCR-antigen recognition impacts on T cell ac ....Exceptions Prove the Rule: How Antigen Recognition Drives T cell Activation. CD8+ T cells are immune cells that are critical for the adaptive immune response, which is central to immune function in vertebrates. CD8+ T cells mediate their effector functions only after activation, which occurs via T cell receptor (TCR) recognition of foreign antigens. Here, unique reagents and sophisticated technologies will be used to define precisely how the nature of TCR-antigen recognition impacts on T cell activation and effector function. This work builds on an earlier identification of an entirely novel mode of TCR-antigen recognition, and its success will establish novel paradigms in T cell biology and represent a key advance in knowledge in the life sciences.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL160100049
Funder
Australian Research Council
Funding Amount
$2,915,738.00
Summary
A molecular investigation into immune function. A molecular investigation into immune function. The project aims to understand how key immune recognition events enable immunity. This project would use a multidisciplinary approach empowered by technological innovations, including the latest advances in atomic and molecular imaging. This research is expected to identify new approaches for the biotechnology industry.
Metabolite- and lipid-based immunity. This project aims to investigate T-cell immunity to lipids and metabolites. The immune system protects hosts from pathogens, and uses T-cells to recognise infected host cells. However, many facets of T-cell function are not understood. This project will unearth the evolutionary and molecular correlates of lipid- and metabolite-based immunity across diverse species. This will provide basic fundamental insights and conceptual advances into a poorly understood, ....Metabolite- and lipid-based immunity. This project aims to investigate T-cell immunity to lipids and metabolites. The immune system protects hosts from pathogens, and uses T-cells to recognise infected host cells. However, many facets of T-cell function are not understood. This project will unearth the evolutionary and molecular correlates of lipid- and metabolite-based immunity across diverse species. This will provide basic fundamental insights and conceptual advances into a poorly understood, but crucial, component of the immune system.Read moreRead less