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Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
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Genetic networks controlling lymphocyte differentiation. White blood cells are produced in the bone marrow from a rare stem cell. This research aims to understand how a handful of master-regulator genes act in the stem cells to produce the white blood cells that are required for our immune response to microbes, vaccination and to prevent cancer.
An investigation into the basis of the T-cell mediated adaptive immune response. Understanding the adaptive immune response to human pathogens is critically important to develop strategies to combat infection. This project will provide a better understanding of how T cells combat viral infection, and will lead to fundamental advances in our understanding of viral immunity and the development of novel immunotherapeutic strategies.
Defining the microenvironmental regulators of spleen function and immunity. The spleen is an important organ that is present in almost all vertebrates and is a critical site for the induction of systemic immune responses. The current paradigms of spleen biology are mostly derived from rodent studies, but the cellular biology of the spleen in humans remains poorly defined. Using novel tools, advanced transcriptomics and imaging techniques this project aims to reveal the functions of stromal cells ....Defining the microenvironmental regulators of spleen function and immunity. The spleen is an important organ that is present in almost all vertebrates and is a critical site for the induction of systemic immune responses. The current paradigms of spleen biology are mostly derived from rodent studies, but the cellular biology of the spleen in humans remains poorly defined. Using novel tools, advanced transcriptomics and imaging techniques this project aims to reveal the functions of stromal cells in the spleen in humans and to define the fundamental roles of spleen stromal cells in long-lived immunity. The anticipated outcomes are to build Australia’s research capacity and to generate new knowledge of significance for our fundamental understanding of the spleen and the role of this tissue in the immune system.Read moreRead less
Atypical T cell receptor recognition of monomorphic CD1 antigen-presenting molecule. T lymphocytes are white blood cells that respond to foreign molecules (antigens). Until recently, most known antigens were proteins. This project will study how T lymphocytes recognise a different class of antigen (glycolipids) that are likely to play an equally important role in the immune system.
Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restricti ....Unrestricted antigen recognition by T lymphocytes. This project aims to investigate the unrestricted T cell repertoire; the molecular and structural basis of antigen recognition by unrestricted T cells; and the development of unrestricted T cells. T lymphocytes typically are restricted to detecting foreign molecules (antigens) on the cell membrane in association with specialised antigen-presenting molecules encoded within the highly polymorphic major histocompatibility (MHC) locus (MHC restriction). T lymphocytes that can recognise antigens in the absence of MHC or MHC like molecules challenges a major paradigm in the field of immunology. As T cell based therapy underpins treatments for cancer and infection, new mechanisms of T cell activation that are independent of patient genotype should ultimately create opportunities for therapeutic and commercial development, leading to both health and economic benefits.Read moreRead less
Understanding heat shock protein complex vaccines. This project aims to understand the mechanism of action and formulation requirements of a novel vaccine technology that utilises heat shock protein complexes. By understanding how this technology works, future vaccines can be improved to induce the immune response required to target specific pathogens, as well as give assurance regarding its safety.
Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic ....Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic substances. Understanding this molecular program of epithelial-immune cell-mediated sensing/repair will be essential to understand how tissue-repair processes can be driven in the lung, an organ critical for respiration and thus life.Read moreRead less
Defining the molecular architecture of a lymphocyte-activating receptor complex. A robust immune response requires activation of sentinel T cells. This project will seek to understand the architecture of receptors at the T cell surface that allow these important immune cells to sense the presence of pathogens that react accordingly.
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