CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to ....CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to these lipids; 2. The cellular receptors that bind to these lipids; 3. The types of lipids involved in this process. This work is essential for us to understand lipid-based immunology which is critical if we ultimately wish to harness this to improve human health.Read moreRead less
Antigen selection mechanisms control T cell immunity against bacteria. CD4+ T (T helper) cells are required to control many important bacterial infections. This Project aims to identify the key targets of CD4+ T cells responding to a model bacterial infection, and to correlate potential antigen effectiveness with native expression, antigen presentation, and the function of antigen-specific CD4+ T cells over time. Our validated experimental 'pipeline' has unprecedented potential to define potent ....Antigen selection mechanisms control T cell immunity against bacteria. CD4+ T (T helper) cells are required to control many important bacterial infections. This Project aims to identify the key targets of CD4+ T cells responding to a model bacterial infection, and to correlate potential antigen effectiveness with native expression, antigen presentation, and the function of antigen-specific CD4+ T cells over time. Our validated experimental 'pipeline' has unprecedented potential to define potent CD4+ T cell antigens within the thousands of proteins expressed by a bacterial pathogen. Our unbiased analysis may help establish the rules that define effective antigenicity. Our work will improve the understanding of bacterial immunity, and inform future design of T-cell based vaccines in the agricultural sector.Read moreRead less
Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that h ....Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that has previously been overlooked. This project aims to understand how this pathway works and how it contributes to the normal workings of cells. This fundamental science has future consequences for the design of vaccines and for the design of therapeutics to treat diseases that show defective interferon signalling.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200100292
Funder
Australian Research Council
Funding Amount
$426,018.00
Summary
Defining the basis of unconventional immune cell development. This project aims to undertake discovery research to characterise the transcriptional programs that underpin the development of unconventional immune cells. This project expects to generate new knowledge in the area of developmental immunology by using cutting-edge molecular and cellular techniques to examine the seeding of immune cells. It is expected that this project will advance our understanding of immune cell biology and the pro ....Defining the basis of unconventional immune cell development. This project aims to undertake discovery research to characterise the transcriptional programs that underpin the development of unconventional immune cells. This project expects to generate new knowledge in the area of developmental immunology by using cutting-edge molecular and cellular techniques to examine the seeding of immune cells. It is expected that this project will advance our understanding of immune cell biology and the programs that control them. Significantly strengthening national excellence in unconventional immune cell research and providing innovative methodology. This should provide significant benefits, such as a comprehensive open-access transcriptional map of developing unconventional immune cells.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100165
Funder
Australian Research Council
Funding Amount
$451,900.00
Summary
Engineering T cells to promote peripheral immunity. Tissue-resident memory T cells (TRM) are key for immune protection against infections and cancer. This has led to much interest in understanding how these immune cells develop, although elucidation of molecules that regulate TRM are still scarce. This project aims to (i) identify genetic drivers of TRM in peripheral organs and (ii) modulate TRM generation utilising state-of-the-art genetic engineering techniques. Expected outcomes include gener ....Engineering T cells to promote peripheral immunity. Tissue-resident memory T cells (TRM) are key for immune protection against infections and cancer. This has led to much interest in understanding how these immune cells develop, although elucidation of molecules that regulate TRM are still scarce. This project aims to (i) identify genetic drivers of TRM in peripheral organs and (ii) modulate TRM generation utilising state-of-the-art genetic engineering techniques. Expected outcomes include generating new knowledge that will contribute to the development of novel therapeutics against infectious disease and cancer, together with the benefit of promoting national and international collaboration with the ultimate goal of improving health.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101031
Funder
Australian Research Council
Funding Amount
$458,120.00
Summary
Defining the structural basis of lipid mediated T cell immunity. This project aims to undertake discovery research to investigate the molecular mechanisms underpinning the role of lipids in T cell immunity: an emerging area of immense biological significance. The anticipated goal is to generate new knowledge in the areas of the life sciences, by using a multidisciplinary approach that includes structural biology, mass spectrometry, biophysics, and cellular immunology, to gain fundamental insight ....Defining the structural basis of lipid mediated T cell immunity. This project aims to undertake discovery research to investigate the molecular mechanisms underpinning the role of lipids in T cell immunity: an emerging area of immense biological significance. The anticipated goal is to generate new knowledge in the areas of the life sciences, by using a multidisciplinary approach that includes structural biology, mass spectrometry, biophysics, and cellular immunology, to gain fundamental insight into molecular determinants that govern lipid mediated immunity. Expected outcomes and benefits of this project include building international and interdisciplinary collaborations to enhance national research capacity, and provide marked advancement of core knowledge in the biological sciences.Read moreRead less
Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and ....Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and death are controlled. It combines methods we developed to track MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling MAIT cell survival/death and increase our fundamental understanding of cell death mechanisms of activated T cells.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100830
Funder
Australian Research Council
Funding Amount
$464,928.00
Summary
Elucidating the genesis of MAIT cell-mediated immunity. T cells develop in the thymus and proceed to survey our body probing molecules that signal if anything is abnormal. A specialised subset of T cells, mucosal associated invariant T (MAIT) cells are crucial in detecting microbial molecules and infection, yet their numbers vary widely between individuals. A key problem is that the factors controlling their development and function are poorly understood. This proposal aims to decode this critic ....Elucidating the genesis of MAIT cell-mediated immunity. T cells develop in the thymus and proceed to survey our body probing molecules that signal if anything is abnormal. A specialised subset of T cells, mucosal associated invariant T (MAIT) cells are crucial in detecting microbial molecules and infection, yet their numbers vary widely between individuals. A key problem is that the factors controlling their development and function are poorly understood. This proposal aims to decode this critical issue in MAIT cell biology, using innovative tools to investigate the molecular basis underpinning their development in the thymus. This work will provide vital, fundamental discoveries into how MAIT cells are produced and regulated, as we ultimately wish to harness MAIT cells to improve human health. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100001
Funder
Australian Research Council
Funding Amount
$875,000.00
Summary
A 3-photon imaging system for deep live imaging. This project aims to establish Australia’s first 3-photon microscope system with adaptive optics for deep intravital imaging. This advanced imaging system will enable researchers to investigate the biology of cells and tissue structures in a wide range of organs and engineered tissues, to a degree not possible with existing technology. This project will capitalise on advanced laser, microscope and adaptive optics technologies with the expected out ....A 3-photon imaging system for deep live imaging. This project aims to establish Australia’s first 3-photon microscope system with adaptive optics for deep intravital imaging. This advanced imaging system will enable researchers to investigate the biology of cells and tissue structures in a wide range of organs and engineered tissues, to a degree not possible with existing technology. This project will capitalise on advanced laser, microscope and adaptive optics technologies with the expected outcomes to include the generation of new knowledge of major biological systems, including the immune system and the nervous system. This will provide significant benefits to fundamental interdisciplinary research into immunology, infectious disease, neuroscience, mechanobiology and engineering.Read moreRead less
Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less