Developing Novel Molecules That Target Hormone Receptors As An Alternative Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$459,867.00
Summary
A promising class of cancer drugs target heat shock protein 90 (Hsp90) and prevent Hsp90 from maintaining its ~100 proteins involved in cell growth. However, all current Hsp90 chemotherapeutics non-selectively target proteins maintained by Hsp90, and induce a cell rescue mechanism involving Hsp70. We describe the development of a novel molecule that will selectively control cell growth and prevent cell rescue via a unique Hsp90 regulated mechanism.
Tapping The Power Of Pluripotency: The Role Of HMGA1 In Stem Cell Self-renewal And Cell Fate Transitions
Funder
National Health and Medical Research Council
Funding Amount
$520,314.00
Summary
Stem-cell-based therapies have great potential as new treatments for degenerative and genetic diseases. However, to ensure we move in the right direction, we need a detailed understanding of stem cell properties. We have recently identified a novel mechanism for controlling stem-cell-like properties in both normal and cancer stem cells. In this project, we will further investigate this new means of controlling stem cells, which could revolutionise future therapeutic strategies for many diseases.
Alternative Splicing- A Regulatory Mechanism Determining Self-renewal And Pluripotency Of ES And IPS Cells
Funder
National Health and Medical Research Council
Funding Amount
$664,650.00
Summary
Stem cells hold great promise in cell replacement therapies and may provide models to study human diseases and to screen new pharmaceuticals. For successful future therapeutic applications, a deeper understanding of the molecular mechanisms governing the behavior of stem cells is crucial. In this proposal we will investigate the role of alternative splicing in the control of the fundamental properties of stem cells, and identify target RNAs and gene expression networks regulated by splicing fact ....Stem cells hold great promise in cell replacement therapies and may provide models to study human diseases and to screen new pharmaceuticals. For successful future therapeutic applications, a deeper understanding of the molecular mechanisms governing the behavior of stem cells is crucial. In this proposal we will investigate the role of alternative splicing in the control of the fundamental properties of stem cells, and identify target RNAs and gene expression networks regulated by splicing factors.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