Expansion Of TGF-beta-Smad Signaling Network And Intrinsic Epithelial-mesenchymal-endothelial Transition
Funder
National Health and Medical Research Council
Funding Amount
$557,297.00
Summary
The majority of tumor death occurs due to tumor metastasis. Both tumor growth and tumor spread require angiogenesis, which is thought to be driven by tumor but originated from host endothelial cells. Could tumor cells behave and function like endothelial cells? This application aims to detect the transition of adult epithelial cells to endothelial cells through a transient mesenchymal state. Our studies should reveal both the molecular and cellular causes of vasculogenic mimicry, thus establishi ....The majority of tumor death occurs due to tumor metastasis. Both tumor growth and tumor spread require angiogenesis, which is thought to be driven by tumor but originated from host endothelial cells. Could tumor cells behave and function like endothelial cells? This application aims to detect the transition of adult epithelial cells to endothelial cells through a transient mesenchymal state. Our studies should reveal both the molecular and cellular causes of vasculogenic mimicry, thus establishing a new paradigm in understanding tumor growth and metastasis. Such novel molecular understanding will open up new anti-tumor therapeutic opportunities.Read moreRead less
Determining The Role Of Rel/NF-kB Transcription Factors In Myeloid Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$500,944.00
Summary
Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB ....Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB proteins, a change in the pattern of gene expression in GMPs leads to an imbalance in production of these two blood cell types that now favours the generation of neutrophils. This work will provide insight into the molecular mechanisms of blood cell development regulated by NF-kB. With disturbances in the balance of blood cell formation representing a hallmark of leukemia, understanding how this process is normally controlled may have important implications for developing therapeutic strategies to combat various types of leukemias.Read moreRead less
What Is The Molecular Mechanism Underlying Cell Death By Necroptosis?
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Recently, we and others have demonstrated that part of the MLKL protein is able to kill cells. This process is known to cause a number of pathologies, including those arising from stroke. Blocking this type of cell death has thus emerged as an attractive therapeutic strategy. However, precisely how MLKL kills cells remains unclear and controversial. In this project, we will resolve these controversies with the goal of an increased fundamental understanding to aid drug discovery.
Mitochondria are both the powerhouses and the poison cupboard of our cells. They have evolved from bacteria and still possess the ability to grow and divide. Unregulated mitochondrial division is seen in dying cells and in cells from patients with neurodegenerative diseases. We have identified new molecules involved in mitochondrial division and are investigating how they function in normal and unhealthy cells.
Role Of Bak And Bax Membrane Anchors In Targeting And Apoptotic Pore Formation.
Funder
National Health and Medical Research Council
Funding Amount
$352,319.00
Summary
In cancer cells the normal process of cell death (called apoptosis) is defective, helping abnormal cells to grow and multiply unchecked. The Bak and Bax proteins are members of the Bcl-2 family of apoptosis regulators, and play a pivotal role in mediating cell death. By defining how these proteins form a pore in mitochondria, the point of no return in cell death, will help the development of novel anti-cancer agents that target the Bcl-2 family in general, and Bak and Bax in particular.
Dynamics of mitochondrial cristae in life and death . This application seeks to use innovative approaches to address how massive structural arrangements in mitochondria are dealt with during normal cell function, and modulated during cell death. The study builds on discoveries made by a team with world-leading expertise in mitochondrial biology and cell death – and brings innovative, cutting-edge techniques in cell biology, proteomics and imaging. The findings will provide new fundamental insig ....Dynamics of mitochondrial cristae in life and death . This application seeks to use innovative approaches to address how massive structural arrangements in mitochondria are dealt with during normal cell function, and modulated during cell death. The study builds on discoveries made by a team with world-leading expertise in mitochondrial biology and cell death – and brings innovative, cutting-edge techniques in cell biology, proteomics and imaging. The findings will provide new fundamental insights into cellular organisation and uncover new principles of communication. Trainees will gain skills in technologies that are highly translatable and in demand in other areas of scientific endeavours. As such the expertise obtained will expand Australian research capabilities.
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Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin ....Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin and its receptor as a novel mechanism driving placentation. Applications for expected project outcomes may include improved breeding of threatened animal species and economically valuable domestic animals as well as improved health care and fertility control for domesticated pets and feral animals. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100830
Funder
Australian Research Council
Funding Amount
$464,928.00
Summary
Elucidating the genesis of MAIT cell-mediated immunity. T cells develop in the thymus and proceed to survey our body probing molecules that signal if anything is abnormal. A specialised subset of T cells, mucosal associated invariant T (MAIT) cells are crucial in detecting microbial molecules and infection, yet their numbers vary widely between individuals. A key problem is that the factors controlling their development and function are poorly understood. This proposal aims to decode this critic ....Elucidating the genesis of MAIT cell-mediated immunity. T cells develop in the thymus and proceed to survey our body probing molecules that signal if anything is abnormal. A specialised subset of T cells, mucosal associated invariant T (MAIT) cells are crucial in detecting microbial molecules and infection, yet their numbers vary widely between individuals. A key problem is that the factors controlling their development and function are poorly understood. This proposal aims to decode this critical issue in MAIT cell biology, using innovative tools to investigate the molecular basis underpinning their development in the thymus. This work will provide vital, fundamental discoveries into how MAIT cells are produced and regulated, as we ultimately wish to harness MAIT cells to improve human health. Read moreRead less
Understanding how mitochondria divide. This project aims to investigate the molecular mechanism by which mitochondria divide. Mitochondria are the powerhouse within our cells, and they grow and divide in our cells to ensure that they are transferred to daughter cells and also so that older mitochondria can be turned over. The project plans to build on the discovery of mitochondrial membrane proteins that are involved in fission. The results of the project could provide fundamental new knowledge ....Understanding how mitochondria divide. This project aims to investigate the molecular mechanism by which mitochondria divide. Mitochondria are the powerhouse within our cells, and they grow and divide in our cells to ensure that they are transferred to daughter cells and also so that older mitochondria can be turned over. The project plans to build on the discovery of mitochondrial membrane proteins that are involved in fission. The results of the project could provide fundamental new knowledge into how the mitochondrial division machine assembles and how mitochondrial fate is determined.Read moreRead less