Bioinks for the 3D printing of cells made from off-the-shelf components. This project aims to develop a simple method for creating complex, multiple-cell-type three-dimensional (3D) cell cultures for in-vitro cell based assays. Using 3D printing technology, this project will develop a versatile polymer system, made from entirely commercially available components, that gels upon printing and has functionality to assist cells in adhering, growing and migrating. The 3D printing of multiple cell typ ....Bioinks for the 3D printing of cells made from off-the-shelf components. This project aims to develop a simple method for creating complex, multiple-cell-type three-dimensional (3D) cell cultures for in-vitro cell based assays. Using 3D printing technology, this project will develop a versatile polymer system, made from entirely commercially available components, that gels upon printing and has functionality to assist cells in adhering, growing and migrating. The 3D printing of multiple cell types will provide biological scientists with more realistic in-vitro cell assays to those found in-vivo. Applications of the research are in cell biology, studying diseases and developing new drugs.Read moreRead less
Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$234,936.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less
Strategies for the detection of designer steroids in racehorses. The Australian racing industry drives economic activity and contributes $1 billion to GDP, $151 million Government revenue and 50,000 jobs in NSW. Racing depends on maintaining the highest standards of integrity. This project will make Australia a world leader by developing robust methods to detect designer steroids in thoroughbred racing.
Structure-function Studies Of Ion Permeation And Selectivity In Recombinant Glycine Receptor Channels
Funder
National Health and Medical Research Council
Funding Amount
$331,300.00
Summary
Ligand-gated ion channels (LGICs) are members of a superfamily of receptor channels, with very significant structural and functional similarities, which play a major role in fast synaptic neurotransmission within the brain and spinal cord, and underlying the complex behaviour of the nervous system, but when dysfunctional can result in major neurological problems. Glycine is one of the two most important inhibitory neurotransmitters in the central nervous system. Impaired glycine-mediated neurotr ....Ligand-gated ion channels (LGICs) are members of a superfamily of receptor channels, with very significant structural and functional similarities, which play a major role in fast synaptic neurotransmission within the brain and spinal cord, and underlying the complex behaviour of the nervous system, but when dysfunctional can result in major neurological problems. Glycine is one of the two most important inhibitory neurotransmitters in the central nervous system. Impaired glycine-mediated neurotransmission underlies a range of inherited neurological diseases and already, it has been shown that the human disorder, familial Startle disease (hyperekplexia) occurs because of point mutations that have impaired the permeation and activation of the glycine receptor (GlyR). Similarly, certain epilepsies are now known to be caused by mutations in, or close to, the channel region in the excitatory acetylcholine receptors (AChRs), which affect channel activation and ion permeation. However, because of their very significant structural and functional similarities, information obtained in one member of the LGIC family of receptors has strong potential application to the other members and the GlyR with its simpler structure has certain advantages for investigation. The first aim of this project is to investigate how the molecular biological structure of these ion channels controls permeation, how it affects how different ions are selectively allowed to move through it and how it affects channel activation. A second related aim is to learn more about the process of desensitization of GlyR receptors, whereby a sustained presence of a high concentration of agonist can cause a reduction in receptor response. A third aim is to specifically investigate the mechanisms underlying the mode of molecular disruption resulting from two new Startle disease mutations, which, in addition to their own inherent clinical value, can also give general information about receptor function.Read moreRead less
Mechanism Of Signal Transduction And Receptor Activation In Ligand Gated Ion Channel Receptors
Funder
National Health and Medical Research Council
Funding Amount
$551,560.00
Summary
This project seeks to provide fundamental new information about the means by which neurotransmitter receptors, which mediate fast synaptic neurotransmission, operate. This knowledge is important since the Cys-loop family of ligand gated ion channel receptors are responsible for a wide range of neuronal signalling and the control of both excitatory and inhibitory receptors. The Cys-loop receptors are modulated by both therapeutic drugs (eg. benzodiazepines, barbiturates, antiemetics) and by recre ....This project seeks to provide fundamental new information about the means by which neurotransmitter receptors, which mediate fast synaptic neurotransmission, operate. This knowledge is important since the Cys-loop family of ligand gated ion channel receptors are responsible for a wide range of neuronal signalling and the control of both excitatory and inhibitory receptors. The Cys-loop receptors are modulated by both therapeutic drugs (eg. benzodiazepines, barbiturates, antiemetics) and by recreational drugs (eg. alcohol, nicotine). They are also targets for development of new therapeutic drugs, such as allosteric modulators of nAChR for memory enhancement, or modulating GlyR to relieve spasticity or chronic pain. The project will use a range of molecular advances made by this and other laboratories to clarify how neurotransmitters enable their receptors to activate and signal. This fundamental information is of major medical significance as defective synaptic transmission, caused by mutations in ligand gated ion channel receptors, gives rise to a number of neurological and psychiatric disease states. The ligand gated receptors are also major targets for therapeutic drugs and the information gained in this study may also provide insights into new ways in which drugs could be used to enhance or inhibit synaptic signalling.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100787
Funder
Australian Research Council
Funding Amount
$331,000.00
Summary
Misspecification in models of economic behaviour. This project aims to develop a robust method for estimation and inference with misspecified economic models. Economic models are designed to test hypotheses about economic behaviour and to estimate key parameters, but their validity and accuracy critically depend on the assumption that the model is correctly specified, which is often doubtful. This project will reparametrize the model to allow for misspecification. The project aims to help modell ....Misspecification in models of economic behaviour. This project aims to develop a robust method for estimation and inference with misspecified economic models. Economic models are designed to test hypotheses about economic behaviour and to estimate key parameters, but their validity and accuracy critically depend on the assumption that the model is correctly specified, which is often doubtful. This project will reparametrize the model to allow for misspecification. The project aims to help modellers produce results that better inform decision-makers and help them make more reliable decisions.Read moreRead less
Mathematical Modelling For Improved Planning Of Infectious Diseases Control Policy
Funder
National Health and Medical Research Council
Funding Amount
$2,750,000.00
Summary
We will develop high-level technical capacity in mathematical modeling of infectious disease transmission and control in Australia, with a focus on research that informs health policy. The aim is to assist Australia to have efficient and effective control strategies and help to prepare us against the threat of emerging infections. Priority areas are vaccination programs, HIV-AIDS, emerging infections and bio-terrorism. Six talented young researchers will be trained by the lead applicant team. To ....We will develop high-level technical capacity in mathematical modeling of infectious disease transmission and control in Australia, with a focus on research that informs health policy. The aim is to assist Australia to have efficient and effective control strategies and help to prepare us against the threat of emerging infections. Priority areas are vaccination programs, HIV-AIDS, emerging infections and bio-terrorism. Six talented young researchers will be trained by the lead applicant team. Together, we will develop a prominent and experienced research team capable of sustaining international quality research into the future. Their work will meet immediate, existing policy needs at state, national and global levels. The program includes the establishment of a Network of Infectious Diseases Modellers of Australia (NIDMA) as a research resource of national expertise, peer support and a means of ongoing communication and collaboration in infectious diseases control. The critical mass of modeling expertise that we create will be sustainable long-term, and will expand to support research concerned with chronic and other non-infectious diseases after the lifetime of the grant.Read moreRead less
Development of new methods to measure in vivo properties of human body tissues. This project will develop new methods of noninvasively measuring the viscoelastic properties of soft tissues in live humans, using a novel magnetic resonance elastography technique. These methods will be applied to study the operation of the human muscle-tendon system, differences in neck muscle properties with age and gender and to measure the properties of the human brain, kidney and liver in vivo. These techniques ....Development of new methods to measure in vivo properties of human body tissues. This project will develop new methods of noninvasively measuring the viscoelastic properties of soft tissues in live humans, using a novel magnetic resonance elastography technique. These methods will be applied to study the operation of the human muscle-tendon system, differences in neck muscle properties with age and gender and to measure the properties of the human brain, kidney and liver in vivo. These techniques may be useful in diagnosing soft tissue disease or injury which are currently difficult to detect using standard imaging techniques. It will also explain how the muscle-tendon unit moves during normal motion in live humans.Read moreRead less
Latent variable modelling of discrete choice experiments. Discrete choice experiments and models are used to forecast consumer responses to changes in products policies and programs worldwide. Recent research suggests key model assumptions are violated because error variances covary with observed and unobserved factors. In order to address this, we will model systematic relationships between error variances and observed (eg, prices, survey length) and unobserved (eg, 'convenience', 'reputation') ....Latent variable modelling of discrete choice experiments. Discrete choice experiments and models are used to forecast consumer responses to changes in products policies and programs worldwide. Recent research suggests key model assumptions are violated because error variances covary with observed and unobserved factors. In order to address this, we will model systematic relationships between error variances and observed (eg, prices, survey length) and unobserved (eg, 'convenience', 'reputation') factors to improve model reliability and accuracy. This should lead to more accurate models/forecasts, benefitting business and government, which addresses the national priority of 'frontier technologies, promoting an innovative culture and economy'.Read moreRead less
Development of a Prothrombogenic Bone Graft Substitute. The clinical demand for bone is massive and to counter this bone can be either harvested from the patient or bone substitutes are used. The success or failure of a bone substitute is determined the instant it come into contact with blood. The surfaces of traditional biomaterials induce a foreign body reaction. The aim of this project is to test the bone forming capacity of a biomaterial that is optimised to produce a natural response from ....Development of a Prothrombogenic Bone Graft Substitute. The clinical demand for bone is massive and to counter this bone can be either harvested from the patient or bone substitutes are used. The success or failure of a bone substitute is determined the instant it come into contact with blood. The surfaces of traditional biomaterials induce a foreign body reaction. The aim of this project is to test the bone forming capacity of a biomaterial that is optimised to produce a natural response from the blood. This response will lead to the formation new viable tissue and eventually bone. Such a material will cause faster bone healing, less pain from graft sites, shorter hospital stays and shorter waiting lists. Read moreRead less