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.
The origins of electroreception and nocturnality in the earliest known jawed vertebrates and their bearing on vertebrate diversification. This project aims to discover primary new data to pinpoint the timing, anatomical origins and phylogenetic significance when two key sensory systems first appeared in modern vertebrates: electroreception and specialised nocturnal vision. Such abilities today allow high diversity of vertebrates to co-exist within the same geographical range, for example on trop ....The origins of electroreception and nocturnality in the earliest known jawed vertebrates and their bearing on vertebrate diversification. This project aims to discover primary new data to pinpoint the timing, anatomical origins and phylogenetic significance when two key sensory systems first appeared in modern vertebrates: electroreception and specialised nocturnal vision. Such abilities today allow high diversity of vertebrates to co-exist within the same geographical range, for example on tropical reefs or rainforest communities, through careful temporal niche partitioning where reliance on other sensory systems takes over from vision and olfaction as the principal method of prey detection. This project aims to elucidate how the modern fish diversity was shaped by such significant early evolutionary events.Read moreRead less
Optimising the spring in your step to enhance footwear design. This project aims to examine how the nervous system adjusts the mechanical function of our feet across a spectrum of speeds, from slow running through to maximal effort sprinting. The proposed research will explore how the nervous system controls the function of the foot to meet the ever-varying demands of locomotion in the real-world. Expected outcomes of this project are to determine if running shoes help or hinder the natural spri ....Optimising the spring in your step to enhance footwear design. This project aims to examine how the nervous system adjusts the mechanical function of our feet across a spectrum of speeds, from slow running through to maximal effort sprinting. The proposed research will explore how the nervous system controls the function of the foot to meet the ever-varying demands of locomotion in the real-world. Expected outcomes of this project are to determine if running shoes help or hinder the natural spring-like function of the foot. It will explain a conceptually novel design allowing shoes to support our feet, whilst harnessing the energetic benefits of the foot's spring-like function. This research has the potential to revolutionise athletic footwear design and has direct implications for enhanced performance in running athletes.Read moreRead less
Resolving evolutionary problems at the fish-tetrapod transition. The project aims to investigate very early Australian tetrapod trackways and conduct fieldwork to resolve the place of origin and timing of the evolution of the first tetrapods. The evolution of fishes to tetrapods was one of the key events in evolution. Studies on Northern Hemisphere fossils place an origin for the group around 380 million years ago. Australian fossils suggest a much older origin. New micro computed tomography dat ....Resolving evolutionary problems at the fish-tetrapod transition. The project aims to investigate very early Australian tetrapod trackways and conduct fieldwork to resolve the place of origin and timing of the evolution of the first tetrapods. The evolution of fishes to tetrapods was one of the key events in evolution. Studies on Northern Hemisphere fossils place an origin for the group around 380 million years ago. Australian fossils suggest a much older origin. New micro computed tomography data from Australian 3-D fossil fishes, combined with study of rare tetrapod gill arch bones, would enable us to determine the origins of tetrapod air-breathing and its ecological setting. The project may facilitate a rewriting of vertebrate evolution's most significant first step.Read moreRead less
Growing up to be supersonic: bat echolocation origins and mechanics. This project aims to address the unresolved evolutionary origins of bat echolocation. Using a unique combination of development, evolution and novel engineering testing, this project expects to generate new insights into how features of the skull have evolved to allow bats to use their senses to interact with the environment. Expected outcomes include the identification of skull features that are unique to echolocating bats and ....Growing up to be supersonic: bat echolocation origins and mechanics. This project aims to address the unresolved evolutionary origins of bat echolocation. Using a unique combination of development, evolution and novel engineering testing, this project expects to generate new insights into how features of the skull have evolved to allow bats to use their senses to interact with the environment. Expected outcomes include the identification of skull features that are unique to echolocating bats and tests of how these relate to the frequency and detection range of sounds produced. Benefits include improved conservation planning for urban and rural bat populations, and potential commercial advances through engineering applications that mimic the biological process of echolocation. Read moreRead less
ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.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 .
New models for the role of chromatin in controlling inducible gene expression. This proposal aims to test novel models of how packaging of DNA in the nucleus plays a fundamental role in gene expression. Understanding these concepts is important in the context of successful gene therapy where major hurdles need to be overcome. This work also has implications for somatic cell therapy since it is important to understand how genes are expressed in order to successfully reprogram cells. Both of these ....New models for the role of chromatin in controlling inducible gene expression. This proposal aims to test novel models of how packaging of DNA in the nucleus plays a fundamental role in gene expression. Understanding these concepts is important in the context of successful gene therapy where major hurdles need to be overcome. This work also has implications for somatic cell therapy since it is important to understand how genes are expressed in order to successfully reprogram cells. Both of these areas are important to the Biotechnology industry. Answering questions about higher order chromatin structure in gene transcription will provide cutting edge, innovative knowledge that will have international significance. 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.
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