Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.
Nanostructured dairy powder for improved functionality. More than 30 per cent of the total milk produced in Australia is converted to powder for export. This project will lead to improvement in the solubility, and hence shelf-life, of protein rich dairy powders which will be of significant economic benefit to the industry. This project will also benefit the wider scientific community in dairy and food sectors.
SARA: Delineating Its Association With The Onset And Development Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$865,972.00
Summary
Liver disease, a significant burden on society, affects many in the prime of their life. Scarring of the liver is a response to injury due to many factors including alcohol, viruses, obesity, and fatty-liver disease. We have identified a protein associated with liver injury. In this project we will perform a systematic analysis to understand the role of this protein in injury progression. Ultimately we intend to develop tools to prevent and treat liver injury.
Molecular Regulation Of Metabolism And Body Composition By Ski Via Crosstalk With Nuclear Hormone Receptor Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Obesity is a common and burdensome health problem in the community which leads to diabetes and heart disease. A number of factors, including hormones play important roles in determing risk of obesity. This study proposes to investigate whether the Ski gene which is a regulatory factor for many hormones affects metabolism in transgenic mouse models of altered Ski function. The proposed studies may identify Ski as a target for therapy for obesity and improvement in sketal muscle metabolism.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$583,477.00
Summary
Ross River virus and chikungunya virus cause muscle and joint pain that can persist for a long time. This project looks at factors in the human host that affect the disease severity, with the aim of finding new treatments.
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