Developing A New Treatment Method To Prevent Lymphopenia Associated With Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$435,939.00
Summary
Sepsis or blood poisoning kills more people than breast cancer, prostate cancer and HIV/AIDS combined. It has a huge economic burden, yet there is no proper diagnostics markers or treatment. One of the main reasons for sepsis-mediated mortality is lack of functioning immune system patients. We have been able to elucidate the molecular mechanism of sepsis-mediated immune cell death and through this project, we aim to develop diagnostics and therapy for treating sepsis-mediated immune suppression.
The balance between cellular survival and death must be tightly regulated. Cells respond to viral infection by self-destructing, thus limiting viral spread to other cells. Viruses have evolved ways to subvert this defensive cell suicide. This project will define and characterise viral factors that maintain host cell survival during infection. These may be targets for the development of new anti-viral therapies and vaccines.
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less
The Mechanism Of Cell Death In Response To Cytoplasmic DNA, And Its Role In Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$517,897.00
Summary
DNA in mammalian cells is in a structure known as the nucleus. Retroviruses such as HIV generate DNA outside the nucleus in the cytoplasm, and detection of DNA in the cytoplasm can lead to cell death, as a defence. All cells carry the remnants of ancient retroviruses in their nuclear DNA. These are normally inactive but may contribute to cancer when activated. This project investigates how normal cells die with cytoplasmic DNA, and whether a defect in this process promotes development of cancer.
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: LE180100001
Funder
Australian Research Council
Funding Amount
$345,475.00
Summary
Pushing the limits of fluorescence microscopy with adaptive optics. This project aims to establish an adaptive optics, super-resolution optical microscopy facility to image cellular events with the highest possible spatial resolution, in a whole cell or tissue context. Sophisticated computer-controlled deformable mirrors will be used to correct the way light is distorted as it passes through specimens, thereby overcoming aberrations found in thick and complex samples. This adaptive optics system ....Pushing the limits of fluorescence microscopy with adaptive optics. This project aims to establish an adaptive optics, super-resolution optical microscopy facility to image cellular events with the highest possible spatial resolution, in a whole cell or tissue context. Sophisticated computer-controlled deformable mirrors will be used to correct the way light is distorted as it passes through specimens, thereby overcoming aberrations found in thick and complex samples. This adaptive optics system will enable researchers to study complex behaviour of biological specimens, at the optical resolution limit in plant and animal tissues, leading to basic biology and biotechnology outcomes in biofuels, biomaterials and biomedicines.Read moreRead less
Understanding how Plasmepsin V directs export of malaria virulence proteins to the host cell. This project aims to characterise how malaria parasites survive and manipulate infected host cells by exporting virulence proteins. This project may identify essential proteins that allow the malaria parasite to transform the host in order to survive, replicate and hide from the immune system and provide new data on protein export in liver-stages.
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101730
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Targeting cell death pathways in parasites. Schistosomiasis is a disease caused by parasitic worms. Due to the potential for drug resistance, new drugs are needed. This project aims to identify the components needed for parasite survival based on a cell death pathway in schistosomes. Neutralising the activities of these proteins should cause parasite death, providing a new treatment strategy.
Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contr ....Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contribute to the development of new generation vaccines and therapies to protect against tissue-specific infectious diseases, cancers and autoimmune diseases.Read moreRead less