About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
Identification Of The Conformation Dependant Targets Of Autoimmune Disease Linked Variation In Human Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,001,815.00
Summary
Specialised immune cells called regulatory T cells act as the policemen of the immune system, preventing the immune system attacking itself, but still fighting infections. If these cells do not work properly, autoimmune diseases such as type 1 diabetes or IBD can arise, because of immune attack on normal body tissue by mistake. In order to explain how this goes wrong we need to carefully identify all of the gene interactions in these cells including interactions over long distances in the DNA.
MicroRNAs are small molecules that modulate the expression of most genes and so affect nearly every biological process and pathology although, they were only discovered in humans less than 10 years ago. The bottleneck in discovering the functions of miRNAs is in identifying their molecular targets, the majority of which remain unknown. We aim to comprehensively identify direct target genes of epithelial-specific microRNAs and to confirm a number of them by gene target validation approaches.
Role Of The MiR-200 Target Quaking In Alternative Splicing During EMT And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$443,160.00
Summary
The spread of cancer to other organs involves cancer cells changing to a more aggressive state and is a major cause of cancer related death. MicroRNAs are a class of genes that control whether cancer cells become more aggressive by regulating other genes. In this project we will examine the function of a new microRNA target which controls the cancer cell aggression. The outcome will be a better understanding of how cancers spread and the identification of new therapeutic targets.
Artificial intelligence algorithms to predict risk of injury in racehorses. This project will address the urgent need for predicting and preventing catastrophic and career limiting limb injuries and cardiac arrhythmias in racehorses due to over (or under) training. Using data from GPS and movement sensors integrated into saddlecloths, artificial intelligence algorithms will convert cumulative data on speed, gait, and stride characteristics during training, along with injury data, into a risk mat ....Artificial intelligence algorithms to predict risk of injury in racehorses. This project will address the urgent need for predicting and preventing catastrophic and career limiting limb injuries and cardiac arrhythmias in racehorses due to over (or under) training. Using data from GPS and movement sensors integrated into saddlecloths, artificial intelligence algorithms will convert cumulative data on speed, gait, and stride characteristics during training, along with injury data, into a risk matrix. Recorded heart rate and ECG data will also be analysed using artificial intelligence to detect early evidence of the development of cardiac arrhythmias. The system will improve racehorse welfare, providing a simple interface to warn trainers when risk of injury becomes high, in order to prevent catastrophic breakdown.Read moreRead less
The migration of cancer cells (metastasis) is responsible for most cancer deaths. Central to this is dynamic organisation of the actin cytoskeleton _ an internal structure that provides cell shape and enables movement. We have identified a family of small molecules (called miR-200) that regulates this actin cytoskeleton through specifically downregulating various genes. We are investigating the nature of these genes and their role in cell motility _ an underlying pre-requisite of metastasis.
Measuring pain in livestock: mechanisms, objective biomarkers and treatments. This project aims to create an objective blood test to measure pain in livestock, and to create a new drug treatment for persistent pain by targeting the immunology of the brain and spinal cord. This project expects to generate new knowledge of the involvement of the neuro-immune system in the creation and maintenance of persistent pain and how this can be quantified through the innovative use of peripheral blood tests ....Measuring pain in livestock: mechanisms, objective biomarkers and treatments. This project aims to create an objective blood test to measure pain in livestock, and to create a new drug treatment for persistent pain by targeting the immunology of the brain and spinal cord. This project expects to generate new knowledge of the involvement of the neuro-immune system in the creation and maintenance of persistent pain and how this can be quantified through the innovative use of peripheral blood tests. Expected outcomes of this project include a blood test capable of quantifying the extent of current pain experience, and a cumulative life measure of pain an animal has experienced. This should provide significant benefits to the Australian livestock industry by improving best practice.Read moreRead less
Liquefaction of silty soils: Micromechanics, modelling and prediction. The project aims to develop a numerical approach to understand liquefaction in silty soils. Liquefaction of silty soils in submarine landslides, mine tailings dam failures and cargo liquefaction in vessels carrying iron/nickel ores can cause property loss and be fatal. This project will bridge the behaviours across the scales and deliver constitutive models that possess grain scale mechanisms for better prediction of liquefac ....Liquefaction of silty soils: Micromechanics, modelling and prediction. The project aims to develop a numerical approach to understand liquefaction in silty soils. Liquefaction of silty soils in submarine landslides, mine tailings dam failures and cargo liquefaction in vessels carrying iron/nickel ores can cause property loss and be fatal. This project will bridge the behaviours across the scales and deliver constitutive models that possess grain scale mechanisms for better prediction of liquefaction induced failure at the large scales. The expected outcomes are liquefaction criteria for silty soils with different silt contents and numerical tools to predict the onset of liquefaction and flow of liquefied soils.Read moreRead less
Road rules for traffic on DNA - gene regulation by encounters between transcribing RNA polymerases and DNA-bound proteins. This project addresses a widespread but poorly understood phenomenon in gene regulation. The work will support Australian industries by supplying new tools for manipulation of gene expression for industrial and medical applications and will provide unique opportunities for Australian students in this emerging field.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less