Negative Regulators Of Nuclear Import; Potential Links To Cancer
Funder
National Health and Medical Research Council
Funding Amount
$495,829.00
Summary
Trafficking of proteins into the nucleus is critical to mammalian cell function, relating strongly to developmental processes and cancer. We have identified a new class of molecule - negative regulators of nuclear import - that function to prevent entry into the nucleus of key regulators of the cell cycle-apoptosis, and have a potential link thereby to cancer. We propose to determine their mechanism of action, modulation by cellular signals, and how important this is to cell function-cancer.
Control Of Organ Size During Development And Disease By The Salvadore-Warts-Hippo Pathway
Funder
National Health and Medical Research Council
Funding Amount
$331,674.00
Summary
Cancer is a disease that results from the generation of too many cells. Many signalling pathways control cell number including the newly identified Salvador-Warts-Hippo pathway. We are studying the mechanisms by which activity of this pathway is controlled, using the vinegar fly as a model. Information obtained from our study will aid understanding of human cancer as cellular processes which go awry in cancer, such as cell proliferation and death, are highly conserved between flies and humans.
Targeting Mechanisms That Promote Cancer Cell Survival: Genetic And Chemical Approaches To Unravel The Molecular Mechanisms That Drive Tumour Formation, Develop Novel Molecular And Chemical Probes, And Discover New Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$751,854.00
Summary
One in three of us are likely to die from cancers. Groundbreaking research, including those made by Prof Huang, has revealed some of the reasons why cancers arise. An attractive way to transform the poor outcomes for cancer patients is to develop better medicines based on findings made by the basic researchers. Prof Huang leads a team at WEHI, including chemists, focused on developing better drugs that exploit knowledge garnered through such basic research in order to improve cancer treatment.
Characterization Of Novel Inhibitors Of G1-S Phase Progression In Drosophila
Funder
National Health and Medical Research Council
Funding Amount
$456,000.00
Summary
Cancer is a disease that affects 1-3 people and therefore, understanding the mechanisms by which cancer arises 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. Many genes involved in cancer have been identified, however, there are likely to be many more genes, that when disrupted or misexpressed can lead to cancer. We are interested in the regulation of cell p ....Cancer is a disease that affects 1-3 people and therefore, understanding the mechanisms by which cancer arises 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. Many genes involved in cancer have been identified, however, there are likely to be many more genes, that when disrupted or misexpressed can lead to cancer. We are interested in the regulation of cell proliferation, and have been studying this in the genetically amenable animal model system, the vinegar fly, Drosophila. A key regulator of cell proliferation in all multicellular organisms is Cyclin E, which is required to drive cells from the G1 (resting state) into S phase (where DNA replication occurs). Correct control of Cyclin E is important in limiting cell proliferation and many cancer-causing mutations result in up-regulation of this critical cell cycle regulator. We have used a genetic approach to identify novel negative regulators of Cyclin E. This proposal seeks to further clarify the mechanism by which the identified Cyclin E interactors regulate cell cycle progression. In addition, this proposal seeks to identify the genes encoding other cyclin E interactors, expected to be novel tumor suppressors. The expected outcome of this project is to elucidate novel genes and mechanisms that control cell proliferation 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
Differentiation Therapy Of Acute Myeloid Leukaemia: Combining RAR-agonists And G-CSF.
Funder
National Health and Medical Research Council
Funding Amount
$449,500.00
Summary
The application of cancer treatments that target specific molecules hold significant promise. However to apply these treatments detailed knowledge is required of the how the molecular targets function in cells. Our previous work using normal blood cells has identified two genes ( MAD1 and p27KIP1 ) that are required for the effects of one such targeted treatment that is aimed at the retinoic acid receptor alpha. We propose to test this treatment in mouse models of human leukaemia and in human le ....The application of cancer treatments that target specific molecules hold significant promise. However to apply these treatments detailed knowledge is required of the how the molecular targets function in cells. Our previous work using normal blood cells has identified two genes ( MAD1 and p27KIP1 ) that are required for the effects of one such targeted treatment that is aimed at the retinoic acid receptor alpha. We propose to test this treatment in mouse models of human leukaemia and in human leukemia cells grown in the laboratory. By deleting the genes for MAD1 and p27KIP1 we will determine if leukaemias lacking these genes fail to respond to treatments targeting the retinoic acid receptor alpha. We will also test if treatments that target retinoic acid receptors in combination with G-CSF, a protein that has previously been demonstrated to have anti-leukaemic activity, can work together to block growth of leukaemic and genetically modified cells. Together these studies will help define classes of leukamias that either will or will not respond to treatments aimed at retinoic acid receptor to better target future leukemia treatments.Read moreRead less