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.
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.
Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation ....Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation using high resolution, single cell methodologies, and to investigate how bio-mechanical forces from contraction or blood flow influence chambers formation.Read moreRead less
Inflammatory skin disorders, such as psoriasis and dermatitis, are responsible for a large burden of human disease and affect people across alldemographics. Knockout (KO) of TNF signalling members in mice is known to induce skin inflammation. This project proposes to use these genetic mouse models to investigate how and why disruption of particular TNF superfamily members leads to disease and potentially identify new targets for treatment.
Cell death is a normal process that permits the growth and defense of our vital tissues. One kind of cell death, necroptosis, is characterised by the swelling and bursting of cells, triggering inflammation. Necroptosis is a key feature of illnesses ranging from colitis to arthritis, and contributes to the brain and heart damage that follows strokes and heart attacks. Understanding necroptotic cell death will pave the way for new therapies for those who suffer from these devastating conditions.
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.
All cells have a characteristic shape (morphology), which is intrinsic to cellular function. A blood cell is designed to move in a liquid medium whereas a muscle cell is optimised for physical movement of attached bones. We are studying the mechanisms which control cell shape. We focus on the components of the cell skeleton (cytoskeleton) which are implicated in the regulation of shape. In particular, we study the actin based microfilament system. We have previously shown that two types of these ....All cells have a characteristic shape (morphology), which is intrinsic to cellular function. A blood cell is designed to move in a liquid medium whereas a muscle cell is optimised for physical movement of attached bones. We are studying the mechanisms which control cell shape. We focus on the components of the cell skeleton (cytoskeleton) which are implicated in the regulation of shape. In particular, we study the actin based microfilament system. We have previously shown that two types of these components of the cytoskeleton are able to control the structure of cells. In addition, we have found that variants of these two components (called isoforms) are used to build structures in different parts of cells. This has led us to think about the anatomy of cells and tissues in a new way. In some ways its like building a city. You create different kinds of buildings to suit their purpose. Each building uses a combination of building blocks which suit the structural demands of rooms and the overall building. In this study we are proposing to identify the specific job that one of these types of building blocks must play in order to allow normal cell growth and embryo development. To do this, we plan to change these genes in mice and then examine the impact on cell and tissue anatomy. This promises to contribute to the conversion of anatomical science and pathology from descriptive to experimental-mechanistic disciplines. This in turn will lead to a new tool set of diagnostic agents for the pathologist and the development of drugs which target specific functions of the cytoskeleton.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100226
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
How innate lymphoid cells regulate mammalian lung development. This project aims to determine the ability of a subset of lung resident immune cells to promote normal lung development through the regulation of stem cells. The lung is constantly exposed to countless environmental challenges including microbes. Mammals’ local immune systems protect the lung from these challenges. This is particularly important in early-life when the lung is still developing. However, impaired lung development affec ....How innate lymphoid cells regulate mammalian lung development. This project aims to determine the ability of a subset of lung resident immune cells to promote normal lung development through the regulation of stem cells. The lung is constantly exposed to countless environmental challenges including microbes. Mammals’ local immune systems protect the lung from these challenges. This is particularly important in early-life when the lung is still developing. However, impaired lung development affects humans and livestock, costing >$3 billion p.a. The intended outcome is to identify basic biological processes involved in normal mammalian lung development, which may lead to strategies to prevent chronic lung diseases in humans and animals.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100165
Funder
Australian Research Council
Funding Amount
$250,000.00
Summary
Electron microscopy cryopreparation facility for biomedical research. The proposed cryopreparation facility will allow cell and molecular biologists and material scientists in the region to prepare samples for ultrastructural research not currently possible due to insufficient local resources, and will thus significantly boost their research. The facility will support a wide range of world class medical and material scientists, including those visiting the Australian Synchrotron, whose research ....Electron microscopy cryopreparation facility for biomedical research. The proposed cryopreparation facility will allow cell and molecular biologists and material scientists in the region to prepare samples for ultrastructural research not currently possible due to insufficient local resources, and will thus significantly boost their research. The facility will support a wide range of world class medical and material scientists, including those visiting the Australian Synchrotron, whose research in health sciences and advanced materials characterisation facilitates the goals of promoting and maintaining good health and frontier technologies. The instrumentation will enhance training capacity in the region and provide young Australian scientists with direct experience of modern electron microscopy techniques.Read moreRead less
The Role Of Necroptosis In Inflammatory Skin Diseases
Funder
National Health and Medical Research Council
Funding Amount
$548,690.00
Summary
Diseases associated with exaggerated inflammation account for a large toll of human disease. We have recently described how mice with a mutation in the Sharpin gene, that causes the chronic proliferative dermatitis phenotype (cpdm), can be rescued by crossing these mice to TNF (Tumor Necrosis Factor) knock-out mice. Our findings suggest that TNF induced cell death, rather than TNF induced cytokine production, may be at the root of many inflammatory diseases and we aim to test this hypothesis in ....Diseases associated with exaggerated inflammation account for a large toll of human disease. We have recently described how mice with a mutation in the Sharpin gene, that causes the chronic proliferative dermatitis phenotype (cpdm), can be rescued by crossing these mice to TNF (Tumor Necrosis Factor) knock-out mice. Our findings suggest that TNF induced cell death, rather than TNF induced cytokine production, may be at the root of many inflammatory diseases and we aim to test this hypothesis in this proposal.Read moreRead less