Discovery Early Career Researcher Award - Grant ID: DE230101012
Funder
Australian Research Council
Funding Amount
$470,789.00
Summary
Redefining how T cell recognition drives T cell activation. This proposal aims to define the key mechanisms that determine how T cells recognise and respond to foreign antigens; a critical feature that defines effective immunity. To achieve this goal, this proposal will leverage multidisciplinary collaborations and innovative methods to understand how structural and biochemical features of T cell receptor recognition influences T cell mediated immunity and development. In turn, this project will ....Redefining how T cell recognition drives T cell activation. This proposal aims to define the key mechanisms that determine how T cells recognise and respond to foreign antigens; a critical feature that defines effective immunity. To achieve this goal, this proposal will leverage multidisciplinary collaborations and innovative methods to understand how structural and biochemical features of T cell receptor recognition influences T cell mediated immunity and development. In turn, this project will facilitate further research and development in the burgeoning field of T cell biology and advance life science research in Australia. Furthermore, as T cell biology is relevant to all vertebrates, this research will greatly benefit the conservation of threatened animal species and agriculture.Read moreRead less
An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the r ....An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the responding T cells. This basic science discovery project will provide substantial new knowledge in the burgeoning field of lipid-mediated immunity, which should ultimately lead to new therapies targeting the CD1a lipid display molecule to either prevent immune mediated damage or promote protective immunity as required.Read moreRead less
Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultim ....Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultimately inform our capacity to better deploy personalised medicines.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
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
Discovery Early Career Researcher Award - Grant ID: DE210100705
Funder
Australian Research Council
Funding Amount
$462,948.00
Summary
Decoding the enigmatic biology of human gamma-delta T cells. The immune system surveys our body examining molecules that signal whether or not everything is ok. T cells are a central to this and use their receptors to monitor these molecular signals. A specialised subset of T cells known as gamma-delta T cells are critical to detecting infection and cancer, yet their fundamental biology is poorly understood. This project aims to unravel this elusive biology. The aims are to understand 1. The div ....Decoding the enigmatic biology of human gamma-delta T cells. The immune system surveys our body examining molecules that signal whether or not everything is ok. T cells are a central to this and use their receptors to monitor these molecular signals. A specialised subset of T cells known as gamma-delta T cells are critical to detecting infection and cancer, yet their fundamental biology is poorly understood. This project aims to unravel this elusive biology. The aims are to understand 1. The diversity in function between gamma-delta T cell subsets, and 2. The diversity in gamma-delta T cell receptors and the molecules that these receptors detect. This work is essential for understanding gamma-delta T cell immunology which is critical if we ultimately wish to harness this to improve human health.Read moreRead less
The molecular basis of T cell receptor cross-reactivity between MHC and MR1. This project aims to investigate how newly discovered immune cells, known as 'MR1T' cells, function in the body. Preliminary evidence shows that MR1T cells can kill stressed cells. This project expects to generate new knowledge describing precisely how MR1T cells target and kill stressed cells. Expected outcomes of this project include to refine research techniques and models, foster interinstitutional collaborations, a ....The molecular basis of T cell receptor cross-reactivity between MHC and MR1. This project aims to investigate how newly discovered immune cells, known as 'MR1T' cells, function in the body. Preliminary evidence shows that MR1T cells can kill stressed cells. This project expects to generate new knowledge describing precisely how MR1T cells target and kill stressed cells. Expected outcomes of this project include to refine research techniques and models, foster interinstitutional collaborations, and further develop our theory on MR1T cell function. This project should provide significant benefits, such as publication of research articles in high impact journals and generation of experimental tools sought after by researchers in the field.Read moreRead less
Deciphering the immune complexity that orchestrates T cell activation. The adaptive immune system consists of a complex cellular network that can efficiently distinguish exogenous required inputs, such as nutrients, from those that are potentially harmful like pathogens. Such ‘friend-foe’ discrimination has its molecular basis in a multitude of receptors with specificity to certain ligands. Critically, however, it is unclear how such discrimination is mechanistically regulated at the functional ....Deciphering the immune complexity that orchestrates T cell activation. The adaptive immune system consists of a complex cellular network that can efficiently distinguish exogenous required inputs, such as nutrients, from those that are potentially harmful like pathogens. Such ‘friend-foe’ discrimination has its molecular basis in a multitude of receptors with specificity to certain ligands. Critically, however, it is unclear how such discrimination is mechanistically regulated at the functional level. We have developed new and sophisticated experimental models that will allow us to systematically dissect and unfold the complexity of the adaptive immune system and address this critical knowledge gap. Expected outcomes will critically advance our general understanding of a fundamental biological principle.Read moreRead less
Whole-body analysis of human tissue-resident memory T cells. T cells provide critical immune protection against infection and cancer, and dysfunctional T cells cause autoimmune disease. Much of our understanding of T cells comes from studies of mice and how these immune cells work in humans is not fully understood. This project aims to determine how human T cells persist and function using a unique organ donor tissue resource. The expected outcomes are to generate fundamental new knowledge about ....Whole-body analysis of human tissue-resident memory T cells. T cells provide critical immune protection against infection and cancer, and dysfunctional T cells cause autoimmune disease. Much of our understanding of T cells comes from studies of mice and how these immune cells work in humans is not fully understood. This project aims to determine how human T cells persist and function using a unique organ donor tissue resource. The expected outcomes are to generate fundamental new knowledge about the regulation of the human immune response. This knowledge is critical for the development of vaccines and immunotherapies designed to harness T cell immunity.Read moreRead less
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