The Role Of Necroptosis In Development, The Immune System And Autoimmune Pathology
Funder
National Health and Medical Research Council
Funding Amount
$454,105.00
Summary
Programmed cell death plays critical roles in development and cell-turnover in the adult. Defects in this process can cause cancer or autoimmune diseases. We will use genetic and biochemical approaches to define the individual roles of necroptosis, a newly described cell death process, and those overlapping with apoptosis in normal development and cell-turnover as well as in cancer and autoimmune diseases. The objective of this work is to identify potential targets for therapeutic intervention i ....Programmed cell death plays critical roles in development and cell-turnover in the adult. Defects in this process can cause cancer or autoimmune diseases. We will use genetic and biochemical approaches to define the individual roles of necroptosis, a newly described cell death process, and those overlapping with apoptosis in normal development and cell-turnover as well as in cancer and autoimmune diseases. The objective of this work is to identify potential targets for therapeutic intervention in cancer or immunopathology.Read moreRead less
A Novel Role For Proteolysis In Promoting Inner Ear Cell Injury And Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$972,818.00
Summary
Nearly 40% of hearing loss is attributable to traumatic noise exposure. This project will test a new idea that cells in the inner ear are damaged and die via noise-induced proteolysis, and investigate whether a similar mechanism operates during age-related hearing loss. It will open new avenues for therapies to preserve hearing where trauma is unavoidable, or has occurred through accident or incident.
Regulation Of Mesenchymal To Epithelial Transitions By Netrin Receptors
Funder
National Health and Medical Research Council
Funding Amount
$646,995.00
Summary
The formation of 2D cellular sheets is important during development, tissue repair, and tumor growth. The mechanisms involved, however, remain largely unknown. Recent findings in the fly and in human cells suggest Frazzled/Neogenin receptors drive this process, by establishing polarised scaffolds in the cell. We will test this hypothesis using fly genetics and analysis of 3-dimensional culture of mammalian cells. Our results will help guide future therapies for human disease.
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.
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.
Molecular Characterisation Of A New Survival Pathway In Haematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$571,631.00
Summary
It is critical for normal health that cells regulate their responses to changes in the the extracellular environment. Receptors on the cell surface are triggered by specific proteins called cytokines, and relay information to the cell interior. These messages include signaling whether cells should survive and proliferate. Inappropriate activation of signals for survival and proliferation is a hallmark of cancer. We are investigating a new survival signal and how this contributes to the survival ....It is critical for normal health that cells regulate their responses to changes in the the extracellular environment. Receptors on the cell surface are triggered by specific proteins called cytokines, and relay information to the cell interior. These messages include signaling whether cells should survive and proliferate. Inappropriate activation of signals for survival and proliferation is a hallmark of cancer. We are investigating a new survival signal and how this contributes to the survival of normal cells and to diseases such as leukaemia.Read moreRead less
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.
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.