Deciphering The Function Of Caspase-2 In DNA Damage Response And Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$808,007.00
Summary
Aberrant cell death and DNA damage response (DDR) are hallmarks of tumourigenesis. Recently we have discovered that an enzyme, caspase-2, previously implicated in cell death execution, also works in DDR and acts as a tumour suppressor. We now wish to validate these finding in preclinical models of cancer and understand precisely how caspase-2 safeguards against cancer development. These studies will help better understand tumourigenesis and may lead to the discovery of new drug targets.
Revealing How The Mammalian Preimplantation Embryo Undergoes Compaction
Funder
National Health and Medical Research Council
Funding Amount
$705,102.00
Summary
The first morphological process critical for mammalian development is embryo compaction. During compaction, cells change their morphology from rounded to wedge-like. The mechanisms controlling embryo compaction remain unclear. We recently discovered that during compaction, cells extend long membrane protrusions on top of each other. In this Project we will establish the role of these protrusion in controlling embryo compaction and reveal the mechanisms underlying their formation.
The Role Of Sidt2 In Cell Proliferation And Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$531,053.00
Summary
This project seeks to understand the function of a gene known as Sidt2. Our preliminary results suggest that Sidt2 not only controls how normal cells divide but also prevents cancer cell growth. We have now engineered mice that lack Sidt2, and will study the cellular and molecular pathways that are disrupted following loss of Sidt2. This work should provide important insights into how both normal and cancer cells grow, and will hopefully identify new targets for anti-cancer treatment.
We have recently discovered that MOZ (monocytic leukaemia zinc finger gene), a gene first identified in rmutations leading to a particularly aggressive form of leukaemia, is a major regulator of senescence. In the absence of MOZ cells exit the cell cycle and become senescent, independently of DNA damage. These obsevations are very important for understanding cancer development because for cancer to grow and spread the cells must avoid senescence.
The Role Of The Polarity Protein, Par3, In Haematopoiesis And Leukaemogenesis
Funder
National Health and Medical Research Council
Funding Amount
$589,777.00
Summary
Understanding the factors regulating blood production is critical to understanding how blood cancers occur and for the development of new therapies. Evidence is emerging of a vital role for the evolutionary conserved ‘polarity’ proteins in blood production and leukaemia This project will elucidate the role of the polarity protein, Par3, in normal and malignant blood cells, providing valuable insight into how Par3 regulates blood formation and the onset and severity of leukaemia.
Role Of Snail Proteins In Mediating Intestinal Stem Cell Identity
Funder
National Health and Medical Research Council
Funding Amount
$646,698.00
Summary
The lining of the intestine is constantly renewed by stem cells which also contribute to replenishment of this layer following damage caused by trauma, infection or treatments such as chemotherapy. We are studying how a family of gene regulators called Snail proteins act to maintain stem cells in the gut. Snail proteins have also been found to be present at high levels in bowel tumours so we are examining their role in the genesis of tumours and resistance to common treatments.
Inflammatory skin disorders, such as psoriasis and dermatitis, are responsible for a large burden of human disease and affect people across alldemographics. Knockout (KO) of TNF signalling members in mice is known to induce skin inflammation. This project proposes to use these genetic mouse models to investigate how and why disruption of particular TNF superfamily members leads to disease and potentially identify new targets for treatment.
Apoptosis And Autophagy In Developmentally Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$502,437.00
Summary
Cell death is essential for sculpting tissues and organs in developing foetus and deregulated cell death results in many diseases. To treat disorders that result from aberrant cell death, we need to understand the control of cell death during development. We will use a vinegar fly model to study cell death modalities in development. By doing this we hope to uncover new knowledge important for human biology and identify new molecules that may be important for understanding and treating disease.
The Role Of The Asymmetric Cell Division Regulator GPSM2 In Mammary Gland Development And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
Tissues are built by small populations of progenitor cells which divide unequally to generate different cell types. Recent studies suggest defective progenitor cells are founders of some breast cancers and that progenitor-like cancer cells resist therapy to regenerate tumours. We have shown a progenitor division regulator called GPSM2 controls these cells and inhibits breast cancer. Examination of this new anti-tumour pathway promises to identify therapeutic targets for breast cancer recurrence.
The Role Of The Pro-survival Bcl-2 Family Member A1 In The Development And Sustained Growth Of Lymphomas.
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
The death of cells, which is regulated by a complex interaction between cell survival and killer proteins, is an important mechanism to prevent cancer. In this proposal we aim to understand the function of one of the cell survival proteins in cancer development and maintenance. This will help to develop novel therapeutic drugs specifically targeting this cell survival protein, thereby eliminating specifically the cancer cells and minimizing collateral damage of healthy tissues.