Who determines gestation length - mother or fetus? This project will extend our knowledge of a key biological process - pregnancy. Variation of gestation length by 10% is generally deleterious to the offspring, and smaller babies have been shown to be more susceptible to later life diseases. Therefore, extension of the information gained from this project will likely impact researchers in species conservation, pest control, and the livestock industries, as well as human, obstetric care and pract ....Who determines gestation length - mother or fetus? This project will extend our knowledge of a key biological process - pregnancy. Variation of gestation length by 10% is generally deleterious to the offspring, and smaller babies have been shown to be more susceptible to later life diseases. Therefore, extension of the information gained from this project will likely impact researchers in species conservation, pest control, and the livestock industries, as well as human, obstetric care and practice. Specifically, knowledge gained from this project may lead to means of limiting (pest control) as well as enhancing (endangered species) species survival.Read moreRead less
Exploitation of a Novel Drug Target for Controlling Animal Trypanosomiasis. Trypanosomiasis greatly reduces livestock productivity in countries where it is endemic and is a threat to livestock and native wildlife in countries such as Australia where it is exotic but there is a risk of entry. New trypanocidal drugs with different modes of action are urgently needed to overcome growing resistance. This project aims to characterise trypanosome tubulin and, with this information, produce new tubulin ....Exploitation of a Novel Drug Target for Controlling Animal Trypanosomiasis. Trypanosomiasis greatly reduces livestock productivity in countries where it is endemic and is a threat to livestock and native wildlife in countries such as Australia where it is exotic but there is a risk of entry. New trypanocidal drugs with different modes of action are urgently needed to overcome growing resistance. This project aims to characterise trypanosome tubulin and, with this information, produce new tubulin-binding compounds for assessment in vitro and in vivo. Upon completion of the project it is expected that drug binding sites on trypanosome tubulin will be characterised and at least one candidate for clinical trials identified.Read moreRead less
Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application i ....Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application in medicine and the drug industry. This research is highly significant in relation to human health. The biological and nutritional aspects of polyunsaturated lipids and dietary fish oils have long been recognized. Thus this project will provide further knowledge that could benefit the health of the nation with consequent reduced health care costs.Read moreRead less
Genes to phenotype: Exploiting the marsupial model. This research will exploit one of Australia's finest natural resources, its marsupial fauna. The features of marsupial reproduction and development provide a unique opportunity to answer fundamental biological questions. This research will show how the minor differences in key developmental genes that have arisen in their 100 million year isolation give rise to the characteristic differences in developmental timing and reproduction between mar ....Genes to phenotype: Exploiting the marsupial model. This research will exploit one of Australia's finest natural resources, its marsupial fauna. The features of marsupial reproduction and development provide a unique opportunity to answer fundamental biological questions. This research will show how the minor differences in key developmental genes that have arisen in their 100 million year isolation give rise to the characteristic differences in developmental timing and reproduction between marsupials and other mammals. The focus on reproduction and development will also provide invaluable knowledge to underpin efforts to conserve our endangered species and to control those that are overabundant.Read moreRead less
Is Calcium part of the mechanism used in glucose signalling in embryogenesis. A vital stage in the development of the embryo is formation of the blastocyst about 4 days after conception. For this to happen the embryo must receive glucose from the mother. We believe that rather being used by the embryo to generate energy, this glucose acts as a signal to switch on the developmental pathway leading to blastocyst formation. Without this signal there is no blastocyst and the pregnancy fails. The pr ....Is Calcium part of the mechanism used in glucose signalling in embryogenesis. A vital stage in the development of the embryo is formation of the blastocyst about 4 days after conception. For this to happen the embryo must receive glucose from the mother. We believe that rather being used by the embryo to generate energy, this glucose acts as a signal to switch on the developmental pathway leading to blastocyst formation. Without this signal there is no blastocyst and the pregnancy fails. The project investigates this signal mechanism. The results will advance understanding of the mechanisms regulating development and in particular link the mother's nutritive status to her fertility during very early pregnancy.Read moreRead less
Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein function ....Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein functions. By doing so, the project will illuminate how haem oxygenase-1 alters cell functions in a beneficial way. This information will eventually assist in preventing the serious disorders associated with deficiency of haem oxygenase-1. It will also provide the basis for novel treatments to slow down age-associated diseases.Read moreRead less
A new paradigm for surfactant composition and function - how do lungs cope with stress? Our research will increase the understanding of the scope of change and precise molecular interactions occurring in the surfactant lipids and proteins of animals under physiological stress. The novel insights will improve the treatment of lung diseases (such as chronic obstructive pulmonary disease and acute lung injury). We have formed a team of international surfactant researchers all experts in state-of-th ....A new paradigm for surfactant composition and function - how do lungs cope with stress? Our research will increase the understanding of the scope of change and precise molecular interactions occurring in the surfactant lipids and proteins of animals under physiological stress. The novel insights will improve the treatment of lung diseases (such as chronic obstructive pulmonary disease and acute lung injury). We have formed a team of international surfactant researchers all experts in state-of-the-art chemical and biophysical technologies relating to surfactant. These collaborations will bring new technological applications to Australia and provide outstanding cross-disciplinary training for postgraduate students and research staff at the interface between animal physiology, biophysical chemistry and respiratory medicine.Read moreRead less
Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will ass ....Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will assess the impact of acute and chronic changes in wall flow and shear on arterial size and function. We will also develop new software which measures other aspects of artery wall behaviour. These basic human physiology studies have direct implications for assessment of artery health in humans.Read moreRead less
Evolvability and the Evolution of Complexity. Anyone engaging in a moment's reflection on the striking richness, diversity, and complexity of the biological world is faced with the question: how did it get here? Though natural selection is central to answering this question, important new work has identified various conditions that make some lineages of organisms "evolvable": capable of changing in ways that radically expand the range of further possible changes. This project will clarify and in ....Evolvability and the Evolution of Complexity. Anyone engaging in a moment's reflection on the striking richness, diversity, and complexity of the biological world is faced with the question: how did it get here? Though natural selection is central to answering this question, important new work has identified various conditions that make some lineages of organisms "evolvable": capable of changing in ways that radically expand the range of further possible changes. This project will clarify and integrate these various conditions using empirical examples and simple models. The resulting work from this project will provide a clearer general understanding of what biological complexity is, and how science has compelling candidates for understanding how it evolves.Read moreRead less
A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a proces ....A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a process that enables single cells to respond to molecules sent from a distance by other cells (TGF-beta signalling). This process is also very important for a host of other biological processes relevant to human health, including cancer.Read moreRead less