Investigation of the biology of insulin-like growth factor 1 and its derivatives for the development of new therapeutics. This project will investigate the biology of insulin-like growth factor 1, a key molecule in growth, development and, in particular, the wound healing process. Its success will lead to improved treatments for non-healing (chronic) wounds and, potentially, new anti-cancer treatments.
How the repair of DNA damage is regulated by IGFBP-3, a protein at the crossroads between cell death and survival. This project aims to discover how a protein called IGFBP-3, which is found in essentially all vertebrates, contributes to the repair of damaged DNA, and to the fate of cells after DNA damage. This is important because all cells are thought to suffer DNA damage many times each day, caused by both environmental and internal events. If unrepaired, this damage can permanently affect a c ....How the repair of DNA damage is regulated by IGFBP-3, a protein at the crossroads between cell death and survival. This project aims to discover how a protein called IGFBP-3, which is found in essentially all vertebrates, contributes to the repair of damaged DNA, and to the fate of cells after DNA damage. This is important because all cells are thought to suffer DNA damage many times each day, caused by both environmental and internal events. If unrepaired, this damage can permanently affect a cell’s genetic make-up. If successful, this research will reveal which other proteins IGFBP-3 interacts with, and how it acts at the crossroads between cell survival or death. This information will advance fundamental understanding about important cellular processes and might in future be applied to improving the response of some diseases to treatment.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100090
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
Three-dimensional cryo electron microscopy facility. The three-dimensional cryo-electron microscopy facility will let us visualise plants, pathogens and nanomachines with resolution not previously possible allowing us to see into cells and diseases with vastly more detail. Our world-class experts will provide regional and national researchers access to cutting-edge technology complementary to the Australian Synchrotron.
Structural investigations into the regulation of programmed cell death. One in three men and one in four women in Australia will develop cancer by the age of 75 at current incidence rates. At its heart, cancer is a disease of uncontrolled cell proliferation. One of the body's main defence mechanisms against excess cell proliferation is Programmed Cell Death, a process which becomes dysfunctional in cancer cells. This work will provide three dimensional images of the machinery that controls Progr ....Structural investigations into the regulation of programmed cell death. One in three men and one in four women in Australia will develop cancer by the age of 75 at current incidence rates. At its heart, cancer is a disease of uncontrolled cell proliferation. One of the body's main defence mechanisms against excess cell proliferation is Programmed Cell Death, a process which becomes dysfunctional in cancer cells. This work will provide three dimensional images of the machinery that controls Programmed Cell Death. This information is critical for the development of drugs designed to re-initiate Programmed Cell Death in cancer cells.Read moreRead less
Cellular mechanisms linking smoking and cardiovascular disease. Everyone develops fatty streaks in their arteries. Why some streaks remain benign, and others progress to clinically-relevant lesions is not completely understood. This project will assess novel cellular mechanisms involved in plaque development, to enable the more effective design of new therapeutic strategies to treat heart disease.
The molecular interactome and functions of circular RNAs. This project aims to identify the functions of circular RNAs, the most contemporary and enigmatic family of RNA molecules. While their abundance suggests they are important, it is unclear how they function at the molecular level. This project aims to delineate circular RNA function by systematically identifying their interacting partners at the DNA, RNA and protein levels, the so-called molecular interactome. This project will reprogram e ....The molecular interactome and functions of circular RNAs. This project aims to identify the functions of circular RNAs, the most contemporary and enigmatic family of RNA molecules. While their abundance suggests they are important, it is unclear how they function at the molecular level. This project aims to delineate circular RNA function by systematically identifying their interacting partners at the DNA, RNA and protein levels, the so-called molecular interactome. This project will reprogram embryonic stem cells to model developmental processes and is designed to validate circular RNA research. Together, the benefits include a higher-quality research workforce by mentoring students, refining fundamental tenets of RNA biology and may extend to improving health in the long-term.Read moreRead less
Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework f ....Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework for Australian and international cell biologists. It will generate new knowledge, train young Australian scientists, help build international collaborative networks and engage the public outside the research community.Read moreRead less
The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify sma ....The core inflammasome as a model for caspase activation. This project aims to change the paradigm for the structure of the active inflammasome. Inflammasomes activate caspases, enzymes central to cell death and inflammatory processes. The current concept of inflammasomes is that caspases are recruited into a single massive protein complex seen as a “speck” in the cell. This project proposes the speck is a terminal stage, after the major enzymatic activity is over. This project aims to purify smaller early stage inflammasome complexes, for structural analysis. The outcome will be a clearer understanding of processes of caspase activation and inflammasome formation. This will provide significant benefits, such as improve our understanding of processes of cell death and innate immunity, and train students.Read moreRead less
Novel models to advance our understanding of mammalian development. This project aims to add to the understanding of cellular processes underpinning mammalian development. Protein phosphorylation is a dynamic process regulated by both protein kinases and protein phosphatases. While the role of kinases in cellular functions are well defined, the roles of protein phosphatases are not well understood. Using a range of laboratory models this project aims to discover the function of the phosphatase P ....Novel models to advance our understanding of mammalian development. This project aims to add to the understanding of cellular processes underpinning mammalian development. Protein phosphorylation is a dynamic process regulated by both protein kinases and protein phosphatases. While the role of kinases in cellular functions are well defined, the roles of protein phosphatases are not well understood. Using a range of laboratory models this project aims to discover the function of the phosphatase PP2A, in cell proliferation, survival, differentiation and DNA damage repair. The anticipated outcome is an improved understanding of all stages of mammalian development. This will provide significant benefits in the biotechnology, chemical and pharmaceutical industries.Read moreRead less
Imaging transcription factors in living mammalian embryos to reveal cell-to-cell variability. The mechanisms controlling how single cells activate different genes are typically studied in cells grown in culture dishes. This project will apply novel imaging methods to study how gene regulatory molecules control cells in living mouse embryos.