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.
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.
Mechanisms For Regulation Of Myc Transcription And Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$645,347.00
Summary
We aim to use the animal model system, the vinegar fly, to investigate mechanism for cancer initiation. The fly has been studied for over 90 years and has proved an excellent genetic model for understanding the complex processes leading to abnormal cell growth, which is associated with the early stages of human cancer. The high level of conservation between fly genes and human cancer genes means these studies will provide novel insights into the genetic mechanisms underlying tumour formation.
Regulation Of Cell Proliferation By The Actin Cytoskeleton
Funder
National Health and Medical Research Council
Funding Amount
$607,795.00
Summary
The architecture of cells defines both their shape and function. It has been known for a long time that cell architecture controls the growth of cells and in particular their capacity to proliferate. We have identified part of the architectural system which controls this process. In this project we will establish how this works and its role in the body. This research will test whether this part of the cell�s architecture is a suitable drug target for the treatment of disorders in cell growth.
Characterising The Mechanisms That Control Blood Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$335,616.00
Summary
Hematopoiesis is a tightly regulated process that provides the body with a constant supply of all the cells of the blood system. My studies aim to characterize the molecular mechanisms that regulate the expansion and differentiation of hematopoietic stem cells (HSCs) into each cell lineage. These studies will be key to the effective use of cellular transplantation therapeutic strategies and aim to provide a greater understanding of the mechanisms that underpin proliferative disorders such as can ....Hematopoiesis is a tightly regulated process that provides the body with a constant supply of all the cells of the blood system. My studies aim to characterize the molecular mechanisms that regulate the expansion and differentiation of hematopoietic stem cells (HSCs) into each cell lineage. These studies will be key to the effective use of cellular transplantation therapeutic strategies and aim to provide a greater understanding of the mechanisms that underpin proliferative disorders such as cancer.Read moreRead less
Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family protei ....Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family proteins in spermatogenesis. The outcomes will define the different roles of highly similar proteins from the same family in differentiation of a single cell lineage. This is important in generating functional tissues using in vitro laboratory approaches or understanding how normal development and developmental disorders arise.Read moreRead less
Understanding the potency and role of individual stem cells in the skin using Rainbow technology. To renew itself, the skin and its components rely on the activity of stem cells. This project will define more precisely the role of each individual stem cell by labelling them with a unique colour and following its fate. This project has the potential to change our current view on how the skin maintains and repairs itself.
Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insig ....Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insights into the molecular regulation of how cells orchestrate and integrate cell death pathways. This should provide significant benefits, such as providing the knowledge base needed to improve our abilities to manipulate cell death both in basic research and commercial applications of cell death.Read moreRead less