How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by wh ....How does clusterin protect cells from stresses? We recently discovered that clusterin: (i) is the only known secreted (ie extracellular) mammalian chaperone and (ii) can protect proteins and cells from stresses.These breakthrough advances provide the first unifying biological function for this protein - in whole organisms, clusterine is likely to protect tissues and organs form biologyical stresses. The work proposed will provide quantum advances in our understanding of the molecular basis by which clusterin effects its protective actions. We expect to demonstrate that clusterin protects cells form stresses by exerting its chaperone action at or near the cell surface and to identify specific regions and structural features of the clusterine molecule important in its chaperone action.Read moreRead less
Control of transcription by the cardiac homeodomain protein Nkx2-5. The transcriptional regulatory protein Nkx2-5, a member of the homeodomain superfamily, is essential for heart development and mutations in the human gene cause congenital heart disease. We seek to define the molecular mechanisms that regulate the transcriptional activity of Nkx2-5. We have previously identified a transcriptional activation domain in the C-terminal region that is bipartite in nature and conserved among Nkx2-5 ....Control of transcription by the cardiac homeodomain protein Nkx2-5. The transcriptional regulatory protein Nkx2-5, a member of the homeodomain superfamily, is essential for heart development and mutations in the human gene cause congenital heart disease. We seek to define the molecular mechanisms that regulate the transcriptional activity of Nkx2-5. We have previously identified a transcriptional activation domain in the C-terminal region that is bipartite in nature and conserved among Nkx2-5 proteins from diverse species. We will characterise the consequences of mutations in this domain in mouse models and search for interacting proteins. Results will advance our understanding of gene regulation in the context of heart disease.Read moreRead less
Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such meta ....Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such metalloproteins and metalloenzymes so that we can better understand their activities with long term aims of creating new molecules for biotechnology and/or drugs.Read moreRead less
Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation tec ....Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation techniques. The project, based on two related equine herpesviruses, will identify new targets for antiviral drugs or vaccines. These herpesvirus BAC systems represent frontier science that greatly facilitates the study of links between genome and phenome.Read moreRead less
Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second ....Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second function of these enzymes, namely their ability to break down organophosphorus-containing insecticides and nerve agents. Ultimately, the structural information resulting from this project may be used in drug design to regulate blood pressure and in engineering proteins for bioremediation.Read moreRead less
The structure and function of dihydroorotase - an enzyme essential for pyrimidine biosynthesis. Malaria has recently re-emerged as one of the major life threatening diseases worldwide. With increasing travel and climate change, malaria is increasingly endangering Australians at home and abroad. Our work aims to provide the basis for the rational design of a new class of anti-malarial drugs by the systematic and thorough analysis of an essential enzyme in the malarial parasite.
The pressures of modern manhood. Mapping the impact of homophobia on the lives of Australian men. this study will construct a detailed map of the impact of homophobia on men;s behaviour, lifestyles and risk-taking (gay or not). It explores the possibility that through devices like taboo and loss of face homophobia can (i) make certain behaviours and life patterns unpalatable and alienate men from safer, healthier behaviours; (ii) block retreat from danger : and (iii) promote risky, antisocial, h ....The pressures of modern manhood. Mapping the impact of homophobia on the lives of Australian men. this study will construct a detailed map of the impact of homophobia on men;s behaviour, lifestyles and risk-taking (gay or not). It explores the possibility that through devices like taboo and loss of face homophobia can (i) make certain behaviours and life patterns unpalatable and alienate men from safer, healthier behaviours; (ii) block retreat from danger : and (iii) promote risky, antisocial, hyper-masculine posturing. from the innovative perspective of the interplay of homophobia with masculinity, we expect to uncover key insights into how homophobia makes an important contribution to the pressures of modern manhood.Read moreRead less
Gender, peacebuilding and the politics of space: a critical examination of United Nations peacebuilding practices. More than half of all peace agreements fail within five years. In response to this dismal statistic, the United Nations (UN) recently began to prioritise gender matters in peacebuilding operations, recognising that gender equality is key to building sustainable peace. This project examines how gender justice is addressed in United Nations peacebuilding policy and practice.
Domestic Subversions: maternalism and cross-cultural histories. This project will assist in the processes of reconciliation, by fostering a sense of a shared history, and increasing public awareness of the complexity of race relations histories in Australia. It will redress a significant gap in Australian knowledge and literature. Very little is known about the history of Aboriginal domestic workers and their relationships with their white employers in Australia, despite growing awareness of the ....Domestic Subversions: maternalism and cross-cultural histories. This project will assist in the processes of reconciliation, by fostering a sense of a shared history, and increasing public awareness of the complexity of race relations histories in Australia. It will redress a significant gap in Australian knowledge and literature. Very little is known about the history of Aboriginal domestic workers and their relationships with their white employers in Australia, despite growing awareness of the significance of domestic service in Aboriginal child removal policies. The project will also assist in establishing Australian historical scholarship at the forefront of leading international research initiatives in gender, race and colonialism studies. Read moreRead less
Inner Eurasia: A World History of Eurasia's Heartlands. Inner Eurasia has played a distinctive and significant role in world history, particularly in the twentieth century when it was the heartland of world communism. Australia's history has been shaped profoundly by the political, military, cultural and commercial impact of the region's great empires. This project will expand Australian understanding of the region, and raise Australia's international visibility and competitiveness in both Inner ....Inner Eurasia: A World History of Eurasia's Heartlands. Inner Eurasia has played a distinctive and significant role in world history, particularly in the twentieth century when it was the heartland of world communism. Australia's history has been shaped profoundly by the political, military, cultural and commercial impact of the region's great empires. This project will expand Australian understanding of the region, and raise Australia's international visibility and competitiveness in both Inner Eurasian and World history. It will attract undergraduate and graduate students and international scholars. Its world history approach will augment Macquarie's significant contributions to the Australian National History Curriculum.Read moreRead less