The Contribution Of Subunit Interfaces To Receptor Activation In Ligand Gated Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$309,070.00
Summary
This project seeks to provide insights into new mechanisms that could be used to enhance or inhibit neuronal signalling. The family of pentameric neurotransmitter receptors that are key components in the process of neuronal signalling and are the target of this study. It will investigate the molecular motions that occur when the receptor shifts from the resting state to the activated state in the presence of neurotransmitter. This critical to understanding the normal function of these receptors ....This project seeks to provide insights into new mechanisms that could be used to enhance or inhibit neuronal signalling. The family of pentameric neurotransmitter receptors that are key components in the process of neuronal signalling and are the target of this study. It will investigate the molecular motions that occur when the receptor shifts from the resting state to the activated state in the presence of neurotransmitter. This critical to understanding the normal function of these receptors in the brain and how they can be modulated.Read moreRead less
Antagonist Of Corticotrophin Releasing Hormone As Therapeutic Agents For The Prevention Of Premature Birth In Humans
Funder
National Health and Medical Research Council
Funding Amount
$376,650.00
Summary
In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow ....In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow the extension of pregnancy term The development of protocols that will in turn reduce neonatal mortality. Additionally we believe that these new agents will be useful in preventing the onset of labour after fetal surgery. Currently there are no effective treatments capable of substantially changing delivery dates. Available therapeutics delay the onset of labour, at best, 24 hours. However, recent exciting results from our laboratories show that rising concentrations of the placental peptide Corticotrophin Releasing Hormone (CRH) are associated with the onset of labour. Further, we have also delayed the onset of labour in pregnant sheep by infusing a relatively insoluble CRH antagonist into the sheep fetus. Labour commenced ONLY AFTER the drug was withdrawn from the mother. This project builds upon an interdisciplinary team: medicinal chemists, molecular modellers, pharmacologists and endocrinologists, to further develop an exciting Australian discovery. Successful completeion of this research will, for the first time, allow the control of pregnancy duration MAXIMISING the benefits to mother and child, reducing mortality and later life morbidities typically associated with premature birth.Read moreRead less
Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms t ....Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms that regulate the signalosomes. The intended outcome is to answer the long-standing question of control of speed and amplitude of innate immune response at the molecular level. Both locally and internationally, this new approach should provide benefits across structural biology, molecular evolution and biotechnology.Read moreRead less
In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-ski ....In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-skilled techniques, including cryo-electron microscopy and single-molecule imaging and holds ancillary benefits to postgraduate students. Anticipated outcomes include influential publications, building a critical mass of expertise in Australia and fostering international collaborations with Australia at the epicentre.Read moreRead less
High-throughput microfluidic approach to mapping hierarchies of interactions in the gene regulation machinery. The exploration of protein-protein interactions networks is becoming an extremely active area of research in life sciences. The current project will develop new approaches to accelerate the discovery of novel interacting proteins participating in gene regulation, in order to understand how cells differentiate into different tissues and organs.
Low Cost High Precision Radiotherapy: A Synergistic Framework For Tumour Tracking During Treatment
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Advances in technology have enabled radiotherapy to become more sophisticated and more efficient at treating cancer. Yet, despite its sophistication, today radiotherapy suffers from a major problem: whilst we routinely image patients prior to treatment, no anatomical information is available during treatment. This project aims to solve this problem by making use of a number of sensors that are already available in a radiotherapy to track the tumours positions during treatment, when it counts.
Single-molecule optofluidics: streamlining high-throughput engineering and analysis of proteins and protein assemblies. This project aims at creating novel technologies for high-throughput engineering and analysis of proteins with single-molecule sensitivity. The platform will considerably accelerate the generation of protein-based diagnostics, new vaccines and therapeutics; it will foster collaborations with industry putting Australia at the forefront of protein research.
Topological order and anyons: quantum engineering of emergent physics. Australia is recognized as one of the world leaders in the area of quantum information and computation. As a frontier technology with tremendous potential but engineering challenges it is vital we expand our theoretical landscape to better steer experimental development. A promising new paradigm is topological quantum computation which uses particles with exotic statistics called anyons that do not exist naturally in three d ....Topological order and anyons: quantum engineering of emergent physics. Australia is recognized as one of the world leaders in the area of quantum information and computation. As a frontier technology with tremendous potential but engineering challenges it is vital we expand our theoretical landscape to better steer experimental development. A promising new paradigm is topological quantum computation which uses particles with exotic statistics called anyons that do not exist naturally in three dimensions but can be engineered to emerge in two dimensional spin lattices. Our bottom up research program would help place Australia at the forefront of these ideas. As a field which combines tools from mathematics, computer science, and physics this project will provide world class training to young researchers.Read moreRead less
The Economic And Social Impacts Of Genetic Sequencing For Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$1,263,576.00
Summary
In this project we will quantify the social and financial costs to families of severe intellectual disability that is genetic in origin. We will assess these impacts in terms of poorer carer health, relationship breakdown, lost income and risk of poverty, as well as increased dependence on government, particularly on welfare payments, and reduced personal income tax paid. We will then determine the extent to which modern clinical genomics can contribute to ameliorating these impacts.
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