Identification Of Novel Tumour Suppressors In Ras-mediated Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$580,504.00
Summary
Cancer is a cooperative process, involving mutations in several genes. Activation of the signaling protein, Ras, contributes to ~30% of human cancers, but alone is not sufficient for tumour formation. The identification of cooperating Tumour Suppressors (TSs), and their analysis in the vinegar fly, Drosophila, mammalian cells and mouse models is key to understanding cancer progression and for the development of therapeutic regimes
Molecular Regulation Of Tumourigenesis By The Polarity Determinant Scribble And Associated Proteins
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have shown that Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we will examine how disruption of Scribble promotes breast cancer using a combination of tissue culture studies and a newly established mouse model. Understanding how this new pathway can regulate breast tumour development may provide novel targets for therapeutic intervention in cancer.
Characterisation Of Cooperation Between Cell Polarity Regulators And Oncogenes In Tumourigenesis Using Drosophila
Funder
National Health and Medical Research Council
Funding Amount
$304,773.00
Summary
Cancers affect 1-3 people at some stage during their lifetime and therefore is of major importance to medical science. Cancers arise through the accumulation of mutations that alter normal cell proliferation control, differentiation, cell death or cell movement. In addition, recent studies have shown that the tumour environment (the interaction between cells) can be a major factor in the development of the cancer. However, this is difficult to study in mammalian models. In this proposal we use t ....Cancers affect 1-3 people at some stage during their lifetime and therefore is of major importance to medical science. Cancers arise through the accumulation of mutations that alter normal cell proliferation control, differentiation, cell death or cell movement. In addition, recent studies have shown that the tumour environment (the interaction between cells) can be a major factor in the development of the cancer. However, this is difficult to study in mammalian models. In this proposal we use the genetically amenable, model system, the vinegar fly Drosophila, to investigate the development of tumours using defined mutations. To explore mechanisms of tumourigenesis in Drosophila, we are using a system where we can make patches (clones) of mutant tissue within the context of normal tissue, a system that more faithfully mimics the development of mammalian cancer. We have observed that certain genes required for cell shape, (cell polarity genes, such as scrib) are important in limiting the action of oncogenes (tumour- causing genes, such as activated alleles of Ras) in the development of tumours in Drosophila. Thus, mutants in cell polarity genes cooperate with oncogenic mutations to result in the generation of invasive tumours. In a genetic screen, we have identified further genes that act in a similar manner to cooperate with mutants in scrib or activated Ras. In this proposal we seek to characterise these genes in tumourigenesis and to explore their mechanism of action. The expected outcome of this project is to elucidate novel genes and mechanisms of tumourigenesis in the context of a whole organism. Due to the conservation of cell proliferation and signalling proteins, this proposal is relevant to understanding human cancer.Read moreRead less
Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.
Developing Novel Molecules That Target Hormone Receptors As An Alternative Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$459,867.00
Summary
A promising class of cancer drugs target heat shock protein 90 (Hsp90) and prevent Hsp90 from maintaining its ~100 proteins involved in cell growth. However, all current Hsp90 chemotherapeutics non-selectively target proteins maintained by Hsp90, and induce a cell rescue mechanism involving Hsp70. We describe the development of a novel molecule that will selectively control cell growth and prevent cell rescue via a unique Hsp90 regulated mechanism.
Tapping The Power Of Pluripotency: The Role Of HMGA1 In Stem Cell Self-renewal And Cell Fate Transitions
Funder
National Health and Medical Research Council
Funding Amount
$520,314.00
Summary
Stem-cell-based therapies have great potential as new treatments for degenerative and genetic diseases. However, to ensure we move in the right direction, we need a detailed understanding of stem cell properties. We have recently identified a novel mechanism for controlling stem-cell-like properties in both normal and cancer stem cells. In this project, we will further investigate this new means of controlling stem cells, which could revolutionise future therapeutic strategies for many diseases.
Alternative Splicing- A Regulatory Mechanism Determining Self-renewal And Pluripotency Of ES And IPS Cells
Funder
National Health and Medical Research Council
Funding Amount
$664,650.00
Summary
Stem cells hold great promise in cell replacement therapies and may provide models to study human diseases and to screen new pharmaceuticals. For successful future therapeutic applications, a deeper understanding of the molecular mechanisms governing the behavior of stem cells is crucial. In this proposal we will investigate the role of alternative splicing in the control of the fundamental properties of stem cells, and identify target RNAs and gene expression networks regulated by splicing fact ....Stem cells hold great promise in cell replacement therapies and may provide models to study human diseases and to screen new pharmaceuticals. For successful future therapeutic applications, a deeper understanding of the molecular mechanisms governing the behavior of stem cells is crucial. In this proposal we will investigate the role of alternative splicing in the control of the fundamental properties of stem cells, and identify target RNAs and gene expression networks regulated by splicing factors.Read moreRead less
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.
Discovery Early Career Researcher Award - Grant ID: DE120101730
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Targeting cell death pathways in parasites. Schistosomiasis is a disease caused by parasitic worms. Due to the potential for drug resistance, new drugs are needed. This project aims to identify the components needed for parasite survival based on a cell death pathway in schistosomes. Neutralising the activities of these proteins should cause parasite death, providing a new treatment strategy.