Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test ....Molecular Mechanisms of NOD signalling. Alterations in NOD1 and NOD2 (nucleotide-binding oligomerization domain containing 1 and 2) signalling have been implicated in various human inflammatory diseases. Therefore, a clear understanding of the molecular signalling pathways is important to gain further insights into potential drug targets for the treatment of these diseases. Using novel experimental approaches, this project aims to identify new members of the NOD signalling pathway. It will test the effect of pharmacological inhibition of established molecules such as RIPK2 or IAPs in NOD dependent models for human diseases. Outcomes of this study will be of the utmost interest for the treatment of NOD driven diseases such as Crohn's disease, Blau syndrome or asthma.Read moreRead less
Toll-like receptors in infectious and inflammatory diseases: the double-edged sword of innate immunity. The innate immune system is the first line of defence against invading microorganisms. This project will explore the role of specific innate immune genes in the control of infections and the development of inflammatory diseases.
Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels ....Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels, and will thereby lead to a greater understanding of the fundamental biological pathways controlling inflammation and defence against infection. This may ultimately lead to commercial opportunities for treating infection and chronic inflammation.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100407
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Biology of immune cells. This project aims to study immune cells that target harmful microbes by recognising by-products of their metabolism, and develop methods modulating their function. In particular, it aims to determine the immune recognition of the full range of microbial metabolites that activate these cells and unravel the mechanisms behind tolerance to nutrition-derived metabolites. This project is a potential opportunity for Australia to maximise its competitive edge in this field and ....Biology of immune cells. This project aims to study immune cells that target harmful microbes by recognising by-products of their metabolism, and develop methods modulating their function. In particular, it aims to determine the immune recognition of the full range of microbial metabolites that activate these cells and unravel the mechanisms behind tolerance to nutrition-derived metabolites. This project is a potential opportunity for Australia to maximise its competitive edge in this field and develop immune-modulatory agents ultimately leading to socioeconomic benefit.Read moreRead less
Understanding T cell immunity induced by infection. We aim to understand how killer T cells are “programmed” upon activation and acquire their characteristic functions and how these are maintained into immunological memory. This proposal will provide insights important for the design and improvement of vaccine strategies to fight pathogens such as influenza, HIV and even tumors.
Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioi ....Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioinformatics to dissect the functions of the lymphoid stromal cells and their roles in the swelling of lymphoid tissues during immune responses. This will provide vital information about the biology of these understudied cells and reveal the ways in which they support the generation of immunity.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100070
Funder
Australian Research Council
Funding Amount
$650,000.00
Summary
An advanced in vivo imaging facility. An advanced in vivo imaging facility: This project will establish an advanced In Vivo Imaging Facility (IVIF) for examining host-microbe interactions and associated immunological processes within the context of the numerous infectious disease models within the University of Melbourne and associated collaborators. The Zeiss LSM 7MP 2-photon imaging system will provide enhanced capacity to directly visualise cellular and molecular events in real time, with gre ....An advanced in vivo imaging facility. An advanced in vivo imaging facility: This project will establish an advanced In Vivo Imaging Facility (IVIF) for examining host-microbe interactions and associated immunological processes within the context of the numerous infectious disease models within the University of Melbourne and associated collaborators. The Zeiss LSM 7MP 2-photon imaging system will provide enhanced capacity to directly visualise cellular and molecular events in real time, with greater sensitivity and in a broader range of tissues and organs. This will provide the opportunity for novel insights into numerous immunological and host-microbe interactions.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: DE120100691
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Argonaute proteins and the mammalian antiviral response. Awarded the Nobel Prize for Medicine in 2006, RNA interference (RNAi) is a natural process that plants use to attack viruses. Humans possess all of the tools for RNAi, but whether it is used for antiviral defense is unknown. This project aims to uncover this immune process which will open new avenues to treat virus infections, from influenza to HIV.
The regulation of anti-viral immunity by host and viral proteins. Anti-viral immunity is initially triggered when specific immune sensors detect viral components within the cell. This project will use a combined functional/structural approach to investigate the specifics of immune activation by a pivotal immune sensor and use this information to understand how influenza A sabotages this specific immune response.