Deciphering The Overlapping Roles Of SSB1 And SSB2 In The Regulation Of Haematopoiesis And Intestinal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$996,631.00
Summary
Our work centres on elucidating the role of two newly identified and related single-stranded DNA binding protein (Ssb1 and Ssb2) in development of blood and gut system. When both genes are deleted mice die with 8 days of knockdown due to bone marrow failure and intestinal atrophy. Our double knockout model parallels the consequences of radiation damage on blood and gut system. Toxicity to these systems is a significant hindrance in delivering anti-tumor therapy.
How Replication Stress Activates The Mitotic Telomere DNA Damage Response To Kill Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$486,467.00
Summary
We discovered a novel mechanism linking stress during DNA replication to difficulties with the cell division process, and identified how this turns on DNA damage response signals from the chromosome ends (i.e. “telomeres”). We have further identified that we can exploit this mechanism to kill cancer cells. In this project we will explore this newly discovered mechanism and identify how it can be targeted for therapeutic purposes.
Defective Repair Of Neuronal Activity-induced DNA Double Strand Breaks: A Novel Pathogenic Mechanism For Neurodegeneration In Ataxia-telangiectasia
Funder
National Health and Medical Research Council
Funding Amount
$570,821.00
Summary
The reason for degeneration of the hindbrain in patients with Ataxia-telangiectasia is unknown. Firing of neurons leads to breaks in the DNA that are normally repaired by ATM, the gene defective in Ataxia-telangiectasia, and failure to reset the system likely leads to abnormal gene expression and cell death. Here we use neuronal cell types derived from patient stem cells to elucidate how this novel disease mechanism may cause hindbrain degeneration and to test drugs that can overcome this.
DNA damage response pathways play important roles in preventing the onset of cancer and regulating the clinical response to chemotherapeutics, and some of the relevant proteins have additional functions during normal development. This fellowship will study new a human protein with key roles in the formation of the lung, and its roles in preventing devastating consequences of normal oxidative damage to DNA, as well as additional fundamental mechanisms involved in preventing genome mutations.
Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.
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