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
Molecular dissection of malaria parasite motility and host-cell invasion across the lifecycle. Malaria parasites move in a unique way, gliding across cell surfaces and infecting host cells using a unique molecular motor. This research aims to understand the molecular mechanics behind parasite movement and use this to develop novel drugs that might throw a spanner in the parasite motor, blocking movement and thereby preventing malaria disease.
Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect ....Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect the cellular conversations that underpin immune protection. Revealing the mechanisms of cellular interactions during an immune response will have a major impact on development of targeted vaccines, and therapeutics (particularly for chronic infections and cancer), which are major health burdens.Read moreRead less
The discovery and characterisation of novel protein regulators of blood cell formation. All of the mature blood cells in the human body are derived from a common ancestor cell type known as a stem cell. Our proposed studies will enhance our knowledge of how functional, mature blood cells are formed from stem cells and how dysregulation of these normally tightly controlled pathways can give rise to severe blood diseases.
Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally inf ....Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally infected or oncogenically transformed cells. Outcomes of this work may contribute to development of novel anti-cancer and anti-viral therapies, diagnostic reagents and vaccines.Read moreRead less
Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outl ....Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outlined will elucidate the process of mitochondrial outer membrane permeabilization, a critical event in cell death by apoptosis, and determine how to kill cells in which this event is blocked.Read moreRead less
Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase ....Role of Histone deacetylase 3 (HDAC3) in intestinal epithelial cell homeostasis and tumorigenesis. Colon cancer is the most common cancer that affects men and women in Australia. Annually, in Victoria alone, more than 3400 people are diagnosed with colon cancer. Colon cancer arises through the accumulation of mutations in key genes over time. Identification of cancer causing genes provides the basis for the design of new cancer therapies. We recently identified a gene called Histone deacetylase 3 (HDAC3) as potentially involved in promoting colon cancer. The current proposal will now extend and validate this finding in mice. Importantly, drugs which inhibit HDAC3 have recently been developed for the treatment of cutaneous T-cell lymphoma. Defining the role HDAC3 plays in colon cancer will justify testing these drugs in colon cancer patients.Read moreRead less
Structural investigations into the regulation of programmed cell death. One in three men and one in four women in Australia will develop cancer by the age of 75 at current incidence rates. At its heart, cancer is a disease of uncontrolled cell proliferation. One of the body's main defence mechanisms against excess cell proliferation is Programmed Cell Death, a process which becomes dysfunctional in cancer cells. This work will provide three dimensional images of the machinery that controls Progr ....Structural investigations into the regulation of programmed cell death. One in three men and one in four women in Australia will develop cancer by the age of 75 at current incidence rates. At its heart, cancer is a disease of uncontrolled cell proliferation. One of the body's main defence mechanisms against excess cell proliferation is Programmed Cell Death, a process which becomes dysfunctional in cancer cells. This work will provide three dimensional images of the machinery that controls Programmed Cell Death. This information is critical for the development of drugs designed to re-initiate Programmed Cell Death in cancer cells.Read moreRead less
The lipidomics of cell fate. This project aims to dissect the roles of lipids in cell fate. The study of lipids, or lipidomics, is an emerging and exciting area of biological science. The fundamental roles of lipids in development remain vastly understudied. This project will look at reprogramming of somatic cells into stem cells, their pluripotency and differentiation. This will be complemented with studies in the zebrafish, which permits the direct study of cell fate in vivo. This approach is ....The lipidomics of cell fate. This project aims to dissect the roles of lipids in cell fate. The study of lipids, or lipidomics, is an emerging and exciting area of biological science. The fundamental roles of lipids in development remain vastly understudied. This project will look at reprogramming of somatic cells into stem cells, their pluripotency and differentiation. This will be complemented with studies in the zebrafish, which permits the direct study of cell fate in vivo. This approach is a powerful way to unlock major events involved in development and to unmask the roles of lipids in these fundamental mechanisms.Read moreRead less
The cell wall substrate delivery mechanisms in plants. This project aims to study the delivery of substrates plants need to biosynthesise sugar polymers. Sugar polymers play key structural and functional roles in plant development and determine quality for all plant-based products including food, textile fibres, building materials and renewable biomass. However, unknown mechanisms regulate and control the transport mechanisms that deliver the building blocks for polysaccharide biosynthesis. This ....The cell wall substrate delivery mechanisms in plants. This project aims to study the delivery of substrates plants need to biosynthesise sugar polymers. Sugar polymers play key structural and functional roles in plant development and determine quality for all plant-based products including food, textile fibres, building materials and renewable biomass. However, unknown mechanisms regulate and control the transport mechanisms that deliver the building blocks for polysaccharide biosynthesis. This project is expected to increase understanding of nucleotide sugar transport and develop and enhance the biological toolbox for applications involving modelling and engineering of plants, synthesis of industrial biopolymers and production of functional foods.Read moreRead less