This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people w ....Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people with prothrombotic pathologies.Read moreRead less
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
Design of dynamic visual signals. Models of the design of visual signals depend heavily upon analyses of static ornaments. Nothing is known about dynamic visual signals. We will use an array of new techniques to tackle this problem for the first time. Motion analyses will define the task faced by the visual system. Sensory limitations will be measured to identify constraints on signal evolution. Digital video playback studies will assess recognition and explain aspects of signal design. Results ....Design of dynamic visual signals. Models of the design of visual signals depend heavily upon analyses of static ornaments. Nothing is known about dynamic visual signals. We will use an array of new techniques to tackle this problem for the first time. Motion analyses will define the task faced by the visual system. Sensory limitations will be measured to identify constraints on signal evolution. Digital video playback studies will assess recognition and explain aspects of signal design. Results will test the generality of principles that have been developed in studies of female mate choice and extend these ideas to address intra-sexual selection operating through opponent assessment.Read moreRead less
Epigenetic Regulation By PKC-theta In Human Breast Cancer Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$818,132.00
Summary
Treating women with advanced breast cancer is difficult, and new drugs are needed to kill the cancer stem cells that cause recurrence. We think that a newly discovered protein, PKC-?, plays an important role in recurring breast cancer and can be targeted using novel ‘epigenetic’ drugs. Here, we will use cutting-edge DNA techniques to learn how this protein controls how cancer cells grow and produce the necessary data to show that targeting this protein is likely to be effective in real patients.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
A Novel Automatic Neural Network Feature Extractor. This project aims to study feature extraction abilities of convolutional as well as traditional neural networks and develop a generic feature extractor which can be applied to wide variety of real-world image and non-image data. New concepts for automatic feature extraction, feature explanation, hybrid evolutionary algorithms and non-iterative ensemble learning will be introduced and evaluated. The expected outcomes are a generic feature extrac ....A Novel Automatic Neural Network Feature Extractor. This project aims to study feature extraction abilities of convolutional as well as traditional neural networks and develop a generic feature extractor which can be applied to wide variety of real-world image and non-image data. New concepts for automatic feature extraction, feature explanation, hybrid evolutionary algorithms and non-iterative ensemble learning will be introduced and evaluated. The expected outcomes are a generic feature extractor for automatically extracting features, an optimiser for finding optimal parameters and non-iterative ensemble learning technique for classification of features into classes. The impact of this project will be automatic feature extractors and classifiers for real-world applications.Read moreRead less
Democratisation of Deep Learning: Neural Architecture Search at Low Cost. The need to manually design Deep Learning-based Neural Networks (DNNs) limits their usage to AI experts and hinders the exploitation of their true potential more broadly, e.g., in farming, humanities. We aim to replace this tedious process through novel AI methods capable of generating DNNs that can perform significantly better and at a lower computational cost than manually designed DNNs. We further expand this idea to so ....Democratisation of Deep Learning: Neural Architecture Search at Low Cost. The need to manually design Deep Learning-based Neural Networks (DNNs) limits their usage to AI experts and hinders the exploitation of their true potential more broadly, e.g., in farming, humanities. We aim to replace this tedious process through novel AI methods capable of generating DNNs that can perform significantly better and at a lower computational cost than manually designed DNNs. We further expand this idea to solve complex real-world problems with both labelled and unlabelled data found in various applications including energy and climate change. The expected outcomes include the novel AI methods, highly trained AI researchers and a number of critical applications that will bring significant benefits to Australia and the world.Read moreRead less