Identifying Novel Genome Instability Signatures In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Cancer is the single biggest clinical problem facing the world. An underlying hallmark of cancer is the accumulation of errors in the genetic information of a cell which arises through genomic instability. This research project aims to investigate novel molecules identified by our screening that function in response to genomic instability in cancer. This study is expected to define roles for each molecule in the maintenance of genomic stability and predict for patient diagnosis and outcome.
Mechanisms Of Regulation Of Ribosome Biogenesis And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
The PI3K/AKT signalling pathway drives many cancers and until recently was thought to do so by preventing cancer cell death. We have shown this pathway also regulates the synthesis of ribosomes, the cellular “factories” that make protein and by interfering with PI3K/AKT regulated ribosome synthesis, can kill cancer cells. We aim to establish the mechanisms underlying this regulation of ribosome synthesis and to test the hypothesis that ribosome biogenesis is a novel target for cancer treatment.
Elucidating Crosstalk Between RhoGTPases And Polarity Proteins: The Interface Between Morphology, Immune Function And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$627,549.00
Summary
Major breakthroughs in cancer and autoimmunity require understanding the molecular basis of by which cell behaviour is controlled. We now know the key molecular players, but still need to determine how they interact within the cell to develop the best treatments and diagnostics. Recent breakthroughs now enable us to “watch” molecular interactions within the cell. We will use these approaches to determine how a key molecular switch is regulated in immune cells and cancer cells.
Investigating The Cellular Requirement For STIM1 Phosphorylation And Store-operated Calcium Entry Suppression During Mitosis: Roles In Development And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$344,900.00
Summary
Cells are constantly interacting with and modifying their surrounding environment. The intracellular calcium signal is one mechanism cells use to translate signals from the microenvironment into cellular responses. This proposal seeks to explore why a key calcium signalling pathway, known as store-operated calcium entry, is specifically silenced during cell division, and to determine how reversing this inhibition affects cell division during normal development and in cancer.
How do mechanical cues regulate tissue renewal and tumour progression? Imbalances between cell production and cell death in tissues can be catastrophic, leading to major global health issues such as cancer. This project will use modified mice and protein-protein interaction based techniques to identify how changes in the mechanical properties of tissues regulate the balance between cell production and cell death.
Tyrosine Kinase Signalling Networks In Pancreatic Cancer: Relevance To Therapeutic Response And Biomarker Development
Funder
National Health and Medical Research Council
Funding Amount
$789,934.00
Summary
Pancreatic cancer is a devastating disease characterized by a lack of effective treatments and biomarkers that identify the best way to treat individual patients. By identifying a novel basis for pancreatic cancer subclassification using cutting edge techniques, we aim to identify therapeutic strategies that can be directed to pancreatic cancer patients in a subgroup-selective manner to ultimately lead to reductions in the morbidity and mortality associated with this devastating disease.
Targetting The CIB1-sphingosine Kinase Interaction In Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$805,034.00
Summary
Sphingosine kinase is a protein involved in cancer development and progression. We have identified that the cancer-inducing activity of sphingosine kinase is controlled by another protein called CIB1 which itself appears involved in causing cancer by deregulating sphingosine kinase. In this study we will examine and target the interaction between sphingosine kinase and CIB1 as a potential therapeutic intervention in cancer.
Integrating Wnt-Apc Pathway With TGF-beta Signalling In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$342,364.00
Summary
Colon cancer is one of the leading causes of death of all cancers. Two molecular pathways have been independently implicated in colon cancer development. Emerging evidences suggest that the two pathways may work together in the colon polypus formation. This application will integrate two separate molecular causes to form a new coherent understanding of cancer development and offer new directions in development of novel colon cancer treatment.
Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims ....Using viral inhibitors to understand the regualtion of apoptosis. Apoptosis is a form of cell death that is critical for the development and well-being of multicellular organisms. The activity of Bak or Bax, two members of the Bcl-2 family, are essential for apoptosis to proceed, but how the activity of these two proteins is regulated is unclear. Many viruses encode inhibitors of apoptosis and the project will make use of two novel viral inhibitors that specifically target Bak. The project aims to determine how the Bak inhibitors function and to provide valuable insights into the normal mechanisms regulating Bak activity.Read moreRead less
Role Of Sphingosine Kinase 1 In PP2A-associated Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$522,994.00
Summary
Defects in protein phosphatase 2A (PP2A) are widely associated with the development of solid tumors and leukemia. The precise mechanisms whereby defects in PP2A lead to cancer, however, remain undefined. We have recently identified that the oncogenic protein sphingosine kinase 1 (SK1) as a target of PP2A. In this study we will examine the role of SK1 in PP2A-associated cancers. Successful outcomes in these studies will establish SK1 as a target for therapeutic intervention in these cancers.