Using Stem Cells And Bioengineered Scaffolds To Promote Regeneration Following Necrotic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$710,857.00
Summary
A number of injuries, including stroke, result in tissue loss. Consequently promoting repair will require restoration of tissue structure, replacement cells and a supportive environment to promote integration of these new cells. This study will engineer and develop novel scaffolds that can replace tissue whilst additionally providing physical and chemical support for newly implanted stem cells. This work will be conducted in an animal model of stroke.
Standardising Protocols For The Differentiation And Integration Of Human Pluripotent Stem Cell-derived Neural Transplants In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$987,664.00
Summary
Clinical trials have shown that transplanting dopamine neurons (specific nerve cells) into the brain of Parkinson’s disease patients can improve symptoms. Trials use fetal tissue for implantation, which is unsustainable and highly variable. This proposal will examine stem cells as an alternative. We will establish a reliable protocol to instruct human stem cells to become dopamine neurons, develop methods to select these cells and, examine the integration of these transplanted cells in the brain
Knowledge, Identification And Exploitation Of Dopaminergic Axon Guidance Cues Will Improve Cell Replacement Therapy For ParkinsonÍs Disease.
Funder
National Health and Medical Research Council
Funding Amount
$481,797.00
Summary
Many obstacles exist for cell transplantation in ParkinsonÍs Disease; namely poor graft survival, restoration of appropriate circuitry and adequate nerve fiber growth from new cells. Using knowledge of how neural circuits are established during fetal development, we will attempt to recapitulate these events following transplantation. Further, we will identify new and novel cues in regulating the connectivity and growth of these nerve fibers.
Regulation Of Neural Progenitor Cell Self-renewal By The RNA-binding Protein ZFP36L1 During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$345,401.00
Summary
The timely differentiation of neural stem cells is critical during development, and the unrestrained proliferation of neural stem cells in the adult can lead to deadly brain cancers such as glioma. At present our understanding of the key molecules that regulate neural stem cell behaviour during these processes remains limited. In this proposal we will investigate the molecular determinants underpinning neural stem cell biology, both within the developing brain, and within glioma.
Validating CaMKK2 As A Rational Treatment Target For Bipolar Disorder
Funder
National Health and Medical Research Council
Funding Amount
$688,175.00
Summary
Bipolar disorder is a disabling, chronic mental illness that profoundly impairs the ability of affected individuals to function in daily life. Existing treatments for bipolar disorder are inadequate and lack the necessary efficacy and tolerability required for long-term therapy. This project will validate the enzyme, CaMKK2, as a rational treatment target for bipolar disorder, which will guide the development of more effective and safer drugs to improve patient outcomes.
Understanding Epigenetic Modification During Oogenesis For Novel Treatments Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Infertility affects about 10% of Australian women and the success rates of current infertility treatments are low due to our poor knowledge of eggs development. The numbers of obese and older women trying to conceive are increasing; fertility treatments are even less effective for them. I have generated mouse models to elucidate the pathways regulating egg development. I will study for alterations in these pathways in the mouse models which perfectly mimic the obesity and aging in women.
A Novel Treatment For Ischemic Stroke: Preclinical Assessment In The Nonhuman Primate
Funder
National Health and Medical Research Council
Funding Amount
$762,246.00
Summary
A major source of repair inhibition after brain injury is debris from dying cells, which contains proteins that hinder repair. This project will examine the expression of these proteins in a clinically-relevant model of ischemic stroke and determine if blocking the effect of these proteins neutralises their repair-inhibiting properties. If successful, there is likelihood that this drug, and method of delivery, could be translated into the human for treatment following an ischemic stroke.
Transcriptional Effectors Of Oncogenic ERK Signaling In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$820,776.00
Summary
This project aims to unravel how one of the most frequently deregulated molecular pathways in colorectal cancer controls the expression of genes required for these tumours to grow and spread. We expect this work to uncover novel therapeutic targets to effectively inactivate this pathway and biomarkers to select patients most likely to benefit from existing therapies.
The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Seizures appear unpredictable and greatly affect the quality of all aspects of life for patients with epilepsy and their carers. New advances in complex systems theory suggest that transitions from normal brain activity to seizures are preceded by measurable changes in the brain’s responses to stimuli, known as critical slowing. Measurement of critical slowing will enable prediction of seizures, providing a warning system, and possibly an opportunity to deliver preventative therapies.