BioPolymer Fibres For Remodelling Mdx And Damaged Muscle
Funder
National Health and Medical Research Council
Funding Amount
$527,286.00
Summary
This project aims to generate new, smart polymers for use in re-building muscle that has degenerated due to disease and-or trauma damage. The merger of smart polymers with biologically based solutions and cells has great potential to improve outcomes of treatments of damaged muscle in diseases such as Muscular Dystrophy.
The Role Of Nuclear Architecture In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$561,966.00
Summary
The goal of the proposed research is to understand how dynamic changes to the chromatin genome packaging network, interact with the DNA damage response and gene expression machinery, to repair damaged DNA and the impact this has on cancer biology. To do so we are combining cutting edge molecular biology techniques with innovative novel microscopy methods developed by our research team, that far exceed the spatiotemporal resolution currently used to study chromatin biology.
Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less
Transgenerational Effects Of Male Obesity - Mechanisms And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$829,143.00
Summary
Childhood obesity is associated with obesity in either parent, and obese children tend to become obese adults, forming an intergenerational cycle that promotes obesity. We have identified paternal obesity as an important novel target for intervention to stop the progression of the obesity epidemic. This project investigates supplementation of obese fathers with folate to prevent the adverse impact of paternal obesity on subsequent generations.
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.
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Long-term Nerve Damage In Cancer Survivors: Identification Of Risk Factors And Optimal Assessment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$850,172.00
Summary
Nerve damage following chemotherapy treatment leads to early treatment cessation and long-lasting disability, developing with commonly used chemotherapies. There is a critical need to understand the mechanisms, optimize clinical assessment and develop interventions to prevent nerve damage. This project is designed to detect the impact of long-term nerve damage in cancer survivors and develop a risk profile based on clinical, neurophysiological and genetic factors.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem ....Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem cell-derived mechanosensory neurons as a platform to extensively study their molecular and functional properties. The significant benefits are the advancement of knowledge in the human mechanosensory system, which to date has been lacking, and in the long-term progress commercial development of novel drugs.Read moreRead less
Ubiquitin And SUMO DNA Damage Response Signalling At Deprotected Telomeres During The Cell Cycle
Funder
National Health and Medical Research Council
Funding Amount
$302,627.00
Summary
Following genome damage cells stop the cell division process and initiate DNA repair. We discovered that at specific times during cell division his does not happen if the damage signals originate from the chromosome ends (i.e. “telomeres”). We anticipate this is necessary to prevent genomic instability in healthy cells and may be driving genomic instability in cancer cells. Experiments described here will elucidate the molecular mechanisms and biological significance of our observation.