Understanding how cells in the olfactory nerve prevent brain infection. The project hypothesis is that the phagocytic activity of olfactory ensheathing cells (OECs) is the key factor that prevents bacteria from accessing the brain via the olfactory nerve, and allows continuous regeneration of the olfactory nervous system. This project aims to investigate how OECs phagocytose bacteria and debris from degenerating axons in vivo, and determine key molecular mechanisms in the process. Thus, we will ....Understanding how cells in the olfactory nerve prevent brain infection. The project hypothesis is that the phagocytic activity of olfactory ensheathing cells (OECs) is the key factor that prevents bacteria from accessing the brain via the olfactory nerve, and allows continuous regeneration of the olfactory nervous system. This project aims to investigate how OECs phagocytose bacteria and debris from degenerating axons in vivo, and determine key molecular mechanisms in the process. Thus, we will characterise an unknown aspect of OEC biology that is neglected in the field. Intended outcomes include a paradigm shift that glial cells, and not circulatory immune cells, are the main defense against microbial invasion of the olfactory nerve. This is relevant for new therapies targeting neural infection/injury and antibiotic usage.Read moreRead less
Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the ....Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the proposed project will develop a novel efficient, safe and notably biodegradable self-adjuvanting delivery system that can be fully customised to match an antigen of choice. This foundational research should provide important advances for commercial immune stimulatory applications.Read moreRead less
Historical frontier violence: drivers, legacy and the role of truth-telling. This project aims to build data to identify the historical factors that incited frontier violence; quantify the legacy on communities today and conduct fieldwork to understand how historical trauma is transmitted across generations. This project expects to develop new knowledge on the circumstances and legacy of settlement and the origins of gaps in life prospects between Indigenous and non-Indigenous Australians. Our e ....Historical frontier violence: drivers, legacy and the role of truth-telling. This project aims to build data to identify the historical factors that incited frontier violence; quantify the legacy on communities today and conduct fieldwork to understand how historical trauma is transmitted across generations. This project expects to develop new knowledge on the circumstances and legacy of settlement and the origins of gaps in life prospects between Indigenous and non-Indigenous Australians. Our expectation is that this will increase public acceptance of the circumstances of settlement and the need to make amends. This project should help increase public support for truth-telling and better relations between Indigenous and non-Indigenous Australians, a vital step towards reconciliation and healing the nation. Read moreRead less
Trails of migration out of Africa in harmful mutations of the First Peoples. This project aims to study harmful mutations specific to Indigenous populations. The process of migration out of Africa has left its footprints in the mutations present in world populations. By investigating these unique signatures, this project aims to characterise the harmful mutations specific to Aboriginal Australians using the whole genome sequences of the First Peoples. The expected outcomes will benefit future ....Trails of migration out of Africa in harmful mutations of the First Peoples. This project aims to study harmful mutations specific to Indigenous populations. The process of migration out of Africa has left its footprints in the mutations present in world populations. By investigating these unique signatures, this project aims to characterise the harmful mutations specific to Aboriginal Australians using the whole genome sequences of the First Peoples. The expected outcomes will benefit future Aboriginal health research to better understand the mutations associated with various genetic diseases.Read moreRead less
Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms cont ....Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms controlling this process. We hypothesise that the local environment of a cell is critical and will involve a combination of particular extracellular matrix and growth factors as well as mechanical tension and the presence of other cell types.Read moreRead less
Acquisition of the mitochondrial genome restores mitochondrial function. The aim of this project is to show that cancer cells with heavily damaged mitochondrial DNA (mtDNA) can acquire the mitochondrial genome from the host and that this results in the recovery of their mitochondrial function. The project is highly significant, as it aims to show in vivo mitochondrial transfer with functional consequences. The project aims to open a new avenue of research and could result in a shift in our under ....Acquisition of the mitochondrial genome restores mitochondrial function. The aim of this project is to show that cancer cells with heavily damaged mitochondrial DNA (mtDNA) can acquire the mitochondrial genome from the host and that this results in the recovery of their mitochondrial function. The project is highly significant, as it aims to show in vivo mitochondrial transfer with functional consequences. The project aims to open a new avenue of research and could result in a shift in our understanding of some features of cellular communication and how cells can overcome unfavourable situations.Read moreRead less
CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research wil ....CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research will provide new data on the fundamental cellular and molecular events that are required to trigger the birth, differentiation and conditions for growth of new neurons in the adult nervous system. The generation of such insights will be critical for any translational research.
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Novel vitamin E analogues disrupt autocrine signalling and angiogenesis: Mechanistic studies and relevance to cancer management. Breast and mesothelioma cancers present a severe problem in Australia and many patients succumb due to lack of appropriate treatment. We believe that vitamin E analogues, selective drugs efficient against cancer cells, hold a promise as future drugs against these two pathologies. Vitamin E analogues act by several mechanisms, including toxic effect on the cancer cells ....Novel vitamin E analogues disrupt autocrine signalling and angiogenesis: Mechanistic studies and relevance to cancer management. Breast and mesothelioma cancers present a severe problem in Australia and many patients succumb due to lack of appropriate treatment. We believe that vitamin E analogues, selective drugs efficient against cancer cells, hold a promise as future drugs against these two pathologies. Vitamin E analogues act by several mechanisms, including toxic effect on the cancer cells and also on cells that are necessary for efficient progression of tumours, such as cells of the malignant blood vessels. Results of this project will be used to prepare clinical testing of these highly promising drugs.Read moreRead less
Developing efficient cancer therapies by targeting of vitamin E analogues to mitochondria. We propose a new strategy of developing efficient anti-cancer agents. Results of this project will lead to establishing highly proising anti-cancer drugs and will open new approaches for the design of novel agents that efficiently kill cancer cells.
Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of ....Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of novel therapies that promote neuronal regeneration relevant for disorders such as spinal cord injury and Alzheimer's disease, which constitute a large socio-economic burden in Australia. Currently, 400 people contract spinal cord injury every year, corresponding to an annual cost of $1 billion, and more than 500 000 aging people suffer from Alzheimer's disease.Read moreRead less