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 Labour commenced ONLY AFTER the drug was withdrawn from the mother.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
Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is ....Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is focused on studying structural features of a range of peptides and their contributions to both activity and to resistance against degradation, with the aim to develop stabilised bioactive peptide sequences for in vivo applications, allowing the full potential of peptides as drugs to be realised.Read moreRead less
Can we engineer plants to grow on salty soils? This project aims to answer questions about how plants can sustain their growth on salty soils. Plant-derived products constitute a pillar for our society. However, crop yields may be severely penalised due to unfavourable growth conditions, including soil salinity. This is particularly relevant for Australia as a large fraction of its arable land is affected by salt. This project aims to use molecular and cell biology techniques to resolve mechanis ....Can we engineer plants to grow on salty soils? This project aims to answer questions about how plants can sustain their growth on salty soils. Plant-derived products constitute a pillar for our society. However, crop yields may be severely penalised due to unfavourable growth conditions, including soil salinity. This is particularly relevant for Australia as a large fraction of its arable land is affected by salt. This project aims to use molecular and cell biology techniques to resolve mechanisms of how the synthesis of cellulose, which constitutes the bulk of a plant's biomass, is maintained in plants during salt stress. This project has potential for climate change mitigation, enhanced plant biomass production and improved fuel security.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100992
Funder
Australian Research Council
Funding Amount
$448,237.00
Summary
New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to devel ....New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to develop novel machine-learning approaches to capture protein flexibility and shape. This proposal will advance fundamental understanding of the TSC-mTOR pathway and build transformative methodologies to study flexible proteins more broadly.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
How Does Fra-1 Regulate The Invasive Properties Of Tumour Cells?
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Most cancer deaths occur when tumours spread and destroy vital body functions. The invasion of tumour cells into surrounding tissue is a critical step during the spread of cancer. This project aims to unravel the molecular mechanisms that control the ability of tumour cells to invade into surrounding tissue and subsequently spread to other sites in the body. We expect to identify potential targets to better diagnose and treat the spread of cancer.
Exploiting Database Technologies for the Visualization and Analysis of Measured and Simulated Plant Structures in Bioinformatics. The project will contribute to both bioinformatics and database research at both the national and international levels, although this project is specifically focusing on plant architecture but it has great potential other fields such as solving computationally difficult problems of branching in nature such as DNA and crystal related research. The results of this resea ....Exploiting Database Technologies for the Visualization and Analysis of Measured and Simulated Plant Structures in Bioinformatics. The project will contribute to both bioinformatics and database research at both the national and international levels, although this project is specifically focusing on plant architecture but it has great potential other fields such as solving computationally difficult problems of branching in nature such as DNA and crystal related research. The results of this research can be applied to all kinds of plants such as rice, cotton, rose etc.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101061
Funder
Australian Research Council
Funding Amount
$424,848.00
Summary
Single particle imaging: x-ray imaging of individual dynamic biomolecules. X-ray lasers produce powerful ultra-short pulses of light that can take temporal snap shots of small radiation-sensitive biological complexes. Thanks to superconducting technology, the next generation of x-ray lasers will be able to produce x-ray pulses at greater rates than ever before. But because of the sheer number of possible molecular configurations, these molecular movies will have only a small amount of data per f ....Single particle imaging: x-ray imaging of individual dynamic biomolecules. X-ray lasers produce powerful ultra-short pulses of light that can take temporal snap shots of small radiation-sensitive biological complexes. Thanks to superconducting technology, the next generation of x-ray lasers will be able to produce x-ray pulses at greater rates than ever before. But because of the sheer number of possible molecular configurations, these molecular movies will have only a small amount of data per frame, posing an enormous challenge for current imaging methods. I aim to meet this challenge by developing an innovative multi-conformational image reconstruction algorithm. This will provide a new window into the molecular dynamics of biological systems, the building blocks of life, and enable rational drug design.Read moreRead less
Understanding The Sources Of Campylobacter In Australia
Funder
National Health and Medical Research Council
Funding Amount
$546,720.00
Summary
Campylobacter is a key cause of foodborne disease in Australia, with rates of illness amongst the highest in the world. Our project brings together academic, government and industry partners to harness new genetic techniques to better identify sources and risk factors for Campylobacter infection. The project will assist health agencies to include genomics in public health, with findings directly informing government policies and industry practices to minimise disease caused by Campylobacter.
Regulation Of Actin Polymerization During Malaria Parasite Invasion Of The Human Erythrocyte
Funder
National Health and Medical Research Council
Funding Amount
$318,147.00
Summary
Malaria parasites depend on successful invasion of red blood cells for their survival. Invasion is powered by a molecular motor based on two key proteins: actin and myosin. Non-specific drugs that inhibit parasite actin block invasion, demonstrating how important its regulation is to parasite success. This project will study several newly identified malaria actin-regulators, aiming to identify new drug targets that will block malaria actin function, stop motility and as such prevent disease.