Characterisation Of SRY Macromolecular Complexes To Provide An Enhanced Understanding Of Human Genetic Sex Reversal And Embryonic Sex Determination
Funder
National Health and Medical Research Council
Funding Amount
$237,360.00
Summary
SRY is the most important gene in the determination of human sex. Mutations in the SRY gene that disrupt its ability to interact with other cellular proteins that regulate its function have shown to result in genetic sex reversal. This project will provide a detailed structural profile of the interfaces that are critical for sex determination, provide a molecular basis for XY-genetic sex reversal, and an enhanced understanding of foetal development.
Mechanisms Regulating Mitochondrial Outer Membrane Permeabilisation During Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$306,562.00
Summary
Apoptosis is a form of cell suicide that is vital in human development and health by removing damaged or unwanted cells in a regulated manner. Disturbances in this pathway are known to be the cause of cancers and other diseases. This research will investigate how the pivotal step in cell death, termed mitochondrial outer membrane permeabilisation (MOMP) is regulated.
The Role Of A New Class Of Chromatin Organising Hub
Funder
National Health and Medical Research Council
Funding Amount
$1,145,450.00
Summary
Within the cell nucleus, specific proteins weave DNA into structured loops that are vital for normal cell function. By studying the molecules involved, we have uncovered a ‘dock’ that controls this DNA architecture. We will define the components and function of this ‘dock’, and the resulting rapid cell death that occurs if it is disrupted. We will explore this cell death pathway thoroughly because we think it may help us to develop new cancer therapies.
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.
Caspase 8 Apoptotic Signalling Induced By The Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$603,126.00
Summary
The death of cells of our body can be an active and purposeful process. Programmed death occurs in response to infection or as a defence against cancerous changes. If a virally infected cell can die prior to replication of the virus, this will control the infection. We have investigated cell death in response to DNA found in the cytoplasm of cells, which can be an indication of infection. The novel cell death pathway we are characterising is relevant to defence against infection and tumours.
Every cell in our body has an intrinsic orientation that is controlled by a universal set of genes known as polarity genes. Loss of this orientation is a common and early feature of cancer. We have identified the gene Scribble as a gene that controls cell orientation and is essential to prevent the development of prostate cancer. We propose experiments to discover how Scribble controls prostate cancer and whether it can be used to better predict outcome for prostate cancer patients.
Role Of Primary Cilia And PCP Proteins In Lens Development: Implications For Lens Regeneration After Cataract Surgery
Funder
National Health and Medical Research Council
Funding Amount
$413,742.00
Summary
Cataract extraction is the most common surgical procedure conducted in our hospitals today. Unfortunately, a complication of surgery is the development of a secondary cataract. This is caused by residual lens epithelial cells undergoing a wound healing response that leads to severe scarring and loss of vision. This project will identify the factors that are needed to maintain lens epithelial cells in a normal state so that they can act as stem cells that can be induced to regenerate a new lens t ....Cataract extraction is the most common surgical procedure conducted in our hospitals today. Unfortunately, a complication of surgery is the development of a secondary cataract. This is caused by residual lens epithelial cells undergoing a wound healing response that leads to severe scarring and loss of vision. This project will identify the factors that are needed to maintain lens epithelial cells in a normal state so that they can act as stem cells that can be induced to regenerate a new lens that can transmit and focus light as normal.Read moreRead less
Dissecting The Embryonic Blood-endothelial Regulatory Code And Investigating Its Role In Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$646,389.00
Summary
Cancer initiating cells acquire stem cell characteristics and multiply within a supportive environment that helps maintain and propagate malignant cells. Identifying the normal hierarchy of gene control within blood stem cells and designing therapies that target cancer cells is the ultimate goal of this body of work.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100200
Funder
Australian Research Council
Funding Amount
$270,427.00
Summary
AutoStem: a high performance, automated stem cell bioengineering facility. This project aims to establish an automated stem cell bioengineering ("AutoStem") facility that will enable critical insights into the molecular mechanisms that underly the loss in stem cell function and tissue homeostasis as we age. The AutoStem facility expects to lead to the discovery of the key drivers of stem cell ageing and the development of novel technological solutions to maintain tissue function with age. The o ....AutoStem: a high performance, automated stem cell bioengineering facility. This project aims to establish an automated stem cell bioengineering ("AutoStem") facility that will enable critical insights into the molecular mechanisms that underly the loss in stem cell function and tissue homeostasis as we age. The AutoStem facility expects to lead to the discovery of the key drivers of stem cell ageing and the development of novel technological solutions to maintain tissue function with age. The outcomes produced from the AutoStem facility will have significant economic and social benefits in enabling healthy ageing and increased productivity for an ageing Australia.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100174
Funder
Australian Research Council
Funding Amount
$400,747.00
Summary
Calcium-mediated regulation of stem cell development. This project aims to clarify the role of syndecan-mediated calcium in stem cell development using Caenorhabditis elegans. Stem cells have great potential for regenerative studies. While stem cells cultures are widely used, we do not fully understand how stem cells develop within an organism. This project expects to uncover the mechanisms underpinning calcium regulation by syndecan in stem cells. The expected outcomes include the optimisation ....Calcium-mediated regulation of stem cell development. This project aims to clarify the role of syndecan-mediated calcium in stem cell development using Caenorhabditis elegans. Stem cells have great potential for regenerative studies. While stem cells cultures are widely used, we do not fully understand how stem cells develop within an organism. This project expects to uncover the mechanisms underpinning calcium regulation by syndecan in stem cells. The expected outcomes include the optimisation of C. elegans stem cell methods to screen calcium regulating compounds and the creation of an in vivo calcium sensor. The project should advance knowledge of the role of syndecans in stem cells and provide the first analysis of in vivo calcium kinetics in stem cells.Read moreRead less