Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four ne ....Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four neuronal cell cultures established with gene-based selection criteria. These cultures will be characterised by gene expression, immunocytochemistry, radiolabelled neurotransmitter release, electrophysiology and Ca2+ imaging studies. This study will highlight the functional effects of gene selection procedures upon stem cell-derived neurons.Read moreRead less
Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nan ....Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nanotechnology would therefore benefit from this work by basing their designs on the principles behind the mechanism of the bacterial motor. This research is also of interest for veterinary science, as motility by flagellar motor is a key virulence factor of common animal pathogens associated with, for example, listeriosis and gastroenteritis.Read moreRead less
Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is call ....Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is called Senile Systemic Amyloidosis (SSA). It is not known how or why this happens. There is no cure or therapy. This project will use transthyretins from human and wallaby to explore a possible cause of SSA. If our hypothesis is correct, we will propose preventative actions to reduce the incidence of SSA in the future.Read moreRead less
Evolution of a protein fold from toxin to physiological regulator: an endogenous potassium channel blocker in humans. A potassium channel blocking peptide employed by sea anemones as a toxic component of their venom is also found in proteins from a number of higher organisms, including man. In most of these proteins the function of this toxin domain is unknown. This project aims to define the structure and function of this domain in a human protein, matrix metalloprotease 23, which has possible ....Evolution of a protein fold from toxin to physiological regulator: an endogenous potassium channel blocker in humans. A potassium channel blocking peptide employed by sea anemones as a toxic component of their venom is also found in proteins from a number of higher organisms, including man. In most of these proteins the function of this toxin domain is unknown. This project aims to define the structure and function of this domain in a human protein, matrix metalloprotease 23, which has possible roles in prostate and other cancers. Our results will not only be of interest in tracing the structural and functional evolution of this toxin domain but will also provide valuable clues to its role in both the normal physiological function of matrix metalloprotease 23, as well as its potential pathological role in cancer.Read moreRead less
Artificial Proteins for the Control of Colloid and Surface Properties. A large amount of Australia's wealth arises from mining and the processing of small (colloidal) particles. This project will develop new coatings for particles, which will allow better control of the properties of particle suspensions. Control of surface properties is also important in the preparation of ceramics and in the preparation of implants and biosensors. The development of new coatings will also offer opportunitie ....Artificial Proteins for the Control of Colloid and Surface Properties. A large amount of Australia's wealth arises from mining and the processing of small (colloidal) particles. This project will develop new coatings for particles, which will allow better control of the properties of particle suspensions. Control of surface properties is also important in the preparation of ceramics and in the preparation of implants and biosensors. The development of new coatings will also offer opportunities for improved performance in these areas.
Many existing coating technologies rely on procedures using organic solvents, which are hazardous to human health and the environment. The proposed research will develop coatings that are made and used in solutions of water only, thereby minimizing pollution production.
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Characterisation of heavy metal transport genes in the plant Arabidopsis: potential roles in metal detoxification and accumulation. Plants have considerable potential for the bioremediation ("phytoremediation") of contaminated soils, including soils polluted with heavy metals. Progress has been made in understanding the physiological and biochemical mechanisms by which plants accumulate and detoxify heavy metals. One important aspect of metal detoxification is the transport of metals across cell ....Characterisation of heavy metal transport genes in the plant Arabidopsis: potential roles in metal detoxification and accumulation. Plants have considerable potential for the bioremediation ("phytoremediation") of contaminated soils, including soils polluted with heavy metals. Progress has been made in understanding the physiological and biochemical mechanisms by which plants accumulate and detoxify heavy metals. One important aspect of metal detoxification is the transport of metals across cell membranes. The recently completed genome project for the model plant Arabidopsis has identified a family of genes encoding heavy metal transport proteins. This project aims to investigate the roles of these genes in metal detoxification. In the longer term this knowledge can be applied to the improvement of phytoremediation processes.Read moreRead less
Insulin-like growth factor binding proteins: structure and ligand interactions. Insulin-like growth factors are important for normal growth and development. Their actions are regulated by a family of IGF binding proteins. In order to understand the mechanism of this regulation, the aim of this project is to determine the 3-dimensional structure of 2 IGFBPs in complex with IGFs. This will lead to a comprehensive understanding of this interaction that promises to provide important basic knowledge ....Insulin-like growth factor binding proteins: structure and ligand interactions. Insulin-like growth factors are important for normal growth and development. Their actions are regulated by a family of IGF binding proteins. In order to understand the mechanism of this regulation, the aim of this project is to determine the 3-dimensional structure of 2 IGFBPs in complex with IGFs. This will lead to a comprehensive understanding of this interaction that promises to provide important basic knowledge as well as having major implications for biotechnology, agriculture and health.Read moreRead less
Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the desig ....Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the design of future biological nano-motors. Our work will provide an understanding of the regulation of this enzyme with potential application in the control of nano-motors.Read moreRead less
In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak protein is a member of the Bcl-2 family of apoptosis regulators, and plays a pivotal role in mediating cell death. By defining each step in Bak-mediated apoptosis, we aim to better understand how cancer cells accumulate, and how targeting the Bcl-2 family may lead to effective anti-cancer therapeutics.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561042
Funder
Australian Research Council
Funding Amount
$852,705.00
Summary
Establishing a high-throughput Protein Production Unit. We seek to establish a world class high-throughput (H-T) protein production unit, the first of its kind in Australia. Throughout the unit robotic technology will be used to build and test protein expression systems as well as drive large scale protein production. The product of the unit will be high quality, pure protein, effective expression systems and world class research. The unit will act as a centre for research into H-T protein ex ....Establishing a high-throughput Protein Production Unit. We seek to establish a world class high-throughput (H-T) protein production unit, the first of its kind in Australia. Throughout the unit robotic technology will be used to build and test protein expression systems as well as drive large scale protein production. The product of the unit will be high quality, pure protein, effective expression systems and world class research. The unit will act as a centre for research into H-T protein expression technology, will underpin the finest biological research, provide the basis for large "structural genomic" type approaches to biological problems and provide a wealth of projects for the Australian synchrotron.Read moreRead less