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
Cellular And Molecular Determinants Of Preleukaemic And Leukaemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$292,635.00
Summary
It has recently become evident that the formation, growth and relapse of many cancers is driven by a rare population of cancer stem cells (CSCs) that have the unique ability to propagate new tumours and are highly resistant to current therapies. However, which normal cells are transformed into CSCs is not known. We will take a potent cancer gene found in leukaemia, and switch it on and off in specific blood cells in mice to determine which healthy cells can be turned into leukaemic stem cells.