Defining The Role Of Kidney CD103+ Dendritic Cells In Kidney Disease For Potential Therapies
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Chronic Kidney Disease (CKD) is a major cause morbidity. Dendritic cells (DCs) play a central role in the development and progression of CKD. This research is based on our recent novel finding in which CD103+ DCs have been defined, for the first time, as a major subset of kidney DCs, and shown to be pathogenic in many kidney diseases. This research will further investigate the role of CD103+ DCs in various types of CKD and aim to develop therapeutic strategies to target CD103+ DCs to treat CKD.
CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the ....CD4 T cell programming by neonatal and early-life infection. T lymphocytes (T cells) are white blood cells that play a critical role in protecting the body from infection. Before T cells can function they need to be programmed so that they can specifically respond to an infectious agent (a type of bacteria or virus). Inappropriate programming can lead to disease. Whether T cells respond to an infectious agent or foreign substance in a protective or destructive manner may critically depend on the age that an individual first encounters the infection. Our project will identify critical periods in life that direct T cell programming to subsequent protective or destructive responses, providing new insights into the developing immune system that may be exploited to treat disease or develop vaccines.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100020
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
Collaborative high bio-containment immunological research facility. Emerging infectious diseases are a serious threat to animals and humans, with most new human infections originating in animals. Our capacity to study these infections and their effects on the immune system is limited. This Facility will provide core equipment for analysis of immune responses to infection at the highest levels of bio-containment.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989226
Funder
Australian Research Council
Funding Amount
$340,000.00
Summary
Multi-photon imaging for infection, immunity, and self recognition. This proposal will address a gap in our imaging capabilities, allowing us to visualise the movement of immune cells and infectious agents such as bacteria and viruses within living tissues. This will immensely improve our capacity to understand interactions between the immune system, invading organisms and the rest of our body. The intravital imaging system will provide novel insights into how the immune system works, which will ....Multi-photon imaging for infection, immunity, and self recognition. This proposal will address a gap in our imaging capabilities, allowing us to visualise the movement of immune cells and infectious agents such as bacteria and viruses within living tissues. This will immensely improve our capacity to understand interactions between the immune system, invading organisms and the rest of our body. The intravital imaging system will provide novel insights into how the immune system works, which will benefit the design of vaccines, the treatment of cancer, and our understanding of allergy. This state-of-the-art facility will also provide vital training in an emerging technology that will have application in many areas of biology.
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Development of novel vaccine delivery systems for induction of mucosal immunity in a large animal model. The induction of mucosal immune responses is a highly desirable goal in vaccine research and development, as it prevents entry of the large number of mucosal pathogens. This proposal aims to develop new mucosal vaccine delivery systems by combining intra-nasal, intra-lung and transcutaneous vaccine delivery with ISCOM-based adjuvants. The nature of the immune response will be analysed in real ....Development of novel vaccine delivery systems for induction of mucosal immunity in a large animal model. The induction of mucosal immune responses is a highly desirable goal in vaccine research and development, as it prevents entry of the large number of mucosal pathogens. This proposal aims to develop new mucosal vaccine delivery systems by combining intra-nasal, intra-lung and transcutaneous vaccine delivery with ISCOM-based adjuvants. The nature of the immune response will be analysed in real time using a sheep cannulation model. Subsequently, the efficacy of mucosal vaccination strategies will be tested in a chlamydia infection model.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
Sphingosine-1-phosphate receptor 5: a novel regulator of T cell immunity. T cells provide critical immune protection against infection and cancer. However, the pathways that regulate these immune cells are not fully understood. T cells express a molecule called S1P5 that has an unknown function in these cells. In this proposal, we reveal new evidence that this molecule is an unappreciated and crucial regulator of T cell behaviour. Using state-of-the-art techniques and novel genetic tools, this p ....Sphingosine-1-phosphate receptor 5: a novel regulator of T cell immunity. T cells provide critical immune protection against infection and cancer. However, the pathways that regulate these immune cells are not fully understood. T cells express a molecule called S1P5 that has an unknown function in these cells. In this proposal, we reveal new evidence that this molecule is an unappreciated and crucial regulator of T cell behaviour. Using state-of-the-art techniques and novel genetic tools, this project aims to discover the involvement of S1P5 in the immune response, and determine how S1P5 can be controlled to enhance protective T cell immunity. The expected outcomes are to generate fundamental new knowledge that will have significance for regulation of the immune response. Read moreRead less
Taking The First Steps From Promise To Product: Exploration Of The Newly Discovered Interleukin 37 Receptor Complex And Its Signaling Pathways
Funder
National Health and Medical Research Council
Funding Amount
$694,623.00
Summary
Cytokines are messenger proteins used by most cells of the body. They function as master regulators of many biological processes and as such play an important role in a wide spectrum of diseases. Anti-inflammatory cytokines attenuate the potentially destructive force of other cytokines and the immune system as a whole, and are therefore coveted as drug targets. We discovered the formidable anti-inflammatory properties of IL-37 and will now explore how these activites can be utilised in clinical ....Cytokines are messenger proteins used by most cells of the body. They function as master regulators of many biological processes and as such play an important role in a wide spectrum of diseases. Anti-inflammatory cytokines attenuate the potentially destructive force of other cytokines and the immune system as a whole, and are therefore coveted as drug targets. We discovered the formidable anti-inflammatory properties of IL-37 and will now explore how these activites can be utilised in clinical medicine.Read moreRead less
Recruitment And Activation Of Alternatively Activated Macrophages By Thioredoxin Peroxidases In Helminth Infections
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
This research will unlock the immunological steps that lead to the development of pathological consequences associated with infectious pathogens and human diseases. The investigation proposed is very timely, as there is a rapid growth in people acquiring infectious diseases in the developing world and inflammatory pathologies in the developed world such as artherosclerosis, asthma, and tumour progression. There is a common denominator between all of these diseases. The body loses its ability to ....This research will unlock the immunological steps that lead to the development of pathological consequences associated with infectious pathogens and human diseases. The investigation proposed is very timely, as there is a rapid growth in people acquiring infectious diseases in the developing world and inflammatory pathologies in the developed world such as artherosclerosis, asthma, and tumour progression. There is a common denominator between all of these diseases. The body loses its ability to regulate a particular type of immune response, termed Th2. This results in the production of a chronic inflammation, which causes lasting damage. We have previously pinpointed the activity of a particular type of white blood cell, the macrophage, as pivotal to the induction of the Th2 immune response. We have also identified a molecule, thioredoxin peroxidase (TPx) that triggers the macrophage to switch on Th2 responses. Once the TPx comes into contact with the surface of the macrophage cell, a series of proteins, called transcription factors become activated in a controlled cascade. This leads to the secretion of substances from the macrophage, which signal the development of Th2. We will identify the mechanism that TPx uses to initiate the process. We propose to investigate this sequence of events by using an in-vitro cell based model to study the enzymatic steps as the macrophage responds to TPx. This goal represents much more than scientific curiosity. A better understanding of the process may reveal how TPx switches on the macrophage. If the trigger for this could be found, it would present a new way to manipulate the macrophage. This will possibly unearth new drug targets and lead to more effective therapeutics against infectious diseases, asthma, artherosclerosis and cancer.Read moreRead less
Development of a prime-boost anti-cancer vaccine. New vaccination strategies are urgently needed for a variety of diseases, including cancer. The problem with cancer vaccines is that it is difficult to trigger a response to a self protein. We propose that a prime-boost vaccination, using yellow fever virus and modified vaccinia virus ankara, could create very strong responses against tumor antigens. This approach can be patented and can revive that field of tumor vaccination, which is currently ....Development of a prime-boost anti-cancer vaccine. New vaccination strategies are urgently needed for a variety of diseases, including cancer. The problem with cancer vaccines is that it is difficult to trigger a response to a self protein. We propose that a prime-boost vaccination, using yellow fever virus and modified vaccinia virus ankara, could create very strong responses against tumor antigens. This approach can be patented and can revive that field of tumor vaccination, which is currently restrained by the difficulty of breaking immunological tolerance. We envisage the construction of a anti-cancer vaccine vector with obvious market potential. An exciting prospect is that this approach could be used as a prophylactic vaccine and possibly also as a therapeutic vaccine.Read moreRead less