Defining Role Of Inflammatory Signals In Enhancing Motoneuron Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$546,688.00
Summary
Spinal cord injury is a devastating event that has a life-long impact on the patient’s life with wide-reaching social and economic effects. In this proposal we examine how inflammatory signals boost neuronal regeneration after injury. Furthermore, we define how new neurons are able to integrate into existing spinal circuitry. Out work provides critical insight and hold keys to unlocking strategies for future restorative therapies in the brain or spinal cord.
Manipulation Of Enteric Neural Stem Cells For Cell Therapy To Treat Enteric Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$611,438.00
Summary
Cell therapy offers great promise for the treatment of motility disorders due to defects in the nerve cells in the bowel. Patient-derived cells are likely to be the best source of cells, however, patient-derived cells will require manipulation because they are likely to be defective. We will identify manipulations of stem/progenitor cells that increase their efficacy for cell transplantation.
Enhancement Of Newborn Neuron Survival To Promote Repair Following Adult Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$555,780.00
Summary
Following brain damage tissue needs to be rebuilt and newborn nerve cells need to survive. Identification of factors that enhance the numbers and promote the survival and appropriate integration of newborn nerve cells is therefore important and over the last few years we have identified two regulatory factors that are prime candidates to enhance numbers and survival of newborn neurons following injury: the Rho pathway and suppressor of cytokine signalling-2, which we will test for effectiveness ....Following brain damage tissue needs to be rebuilt and newborn nerve cells need to survive. Identification of factors that enhance the numbers and promote the survival and appropriate integration of newborn nerve cells is therefore important and over the last few years we have identified two regulatory factors that are prime candidates to enhance numbers and survival of newborn neurons following injury: the Rho pathway and suppressor of cytokine signalling-2, which we will test for effectiveness following brain injury.Read moreRead less
Neurons within the wall of the bowel play an essential role in gut motility. A number of motility disorders are caused by diseased enteric neurons, but there are currently no effective treatments for these diseases. We will use animal models of a pediatric motility disorder to examine whether stem cells implanted into the colon can generate neurons and restore normal motility.
Identification Of Novel Epigenetic Modifiers Involved In Neural Stem Cell Function And Glioblastoma
Funder
National Health and Medical Research Council
Funding Amount
$748,680.00
Summary
The brain is produced from stem cells that have the capacity to make all the mature cells in the brain, both during development, and after injury. Brain stem cells are of interest due to the therapeutic potential to alter their function for regenerative medicine or treatment of neurodegenerative disorders. These stem cells also have characteristics in common with brain tumour cells. We seek to identify genes important in brain stem cells and brain tumours, in order to identify new targets for th ....The brain is produced from stem cells that have the capacity to make all the mature cells in the brain, both during development, and after injury. Brain stem cells are of interest due to the therapeutic potential to alter their function for regenerative medicine or treatment of neurodegenerative disorders. These stem cells also have characteristics in common with brain tumour cells. We seek to identify genes important in brain stem cells and brain tumours, in order to identify new targets for therapy.Read moreRead less
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.
Building An Immunocompetent Alzheimer’s Disease Brain-on-a-chip
Funder
National Health and Medical Research Council
Funding Amount
$458,937.00
Summary
New human cell culture models of Alzheimer's disease are urgently needed to help translate drugs into successful patient outcomes. In this proposal we will develop an Alzheimer's disease brain-on-a-chip that contains the major human brain cell types and neuropathological features of the Alzheimer's. We will demonstrate the applicability of the model for identifying new Alzheimer's disease drugs and diagnostics and show that the model can be readily adopted by Australian Alzheimer's researchers.
Neogenin: A Molecular Determinant Of Neural Progenitor Polarity And Function
Funder
National Health and Medical Research Council
Funding Amount
$569,296.00
Summary
The neuroepithelium (NEP) contains the embryonic neural stem cells essential for the production of all neurons in the adult brain. Failure in NEP function leads to devastating neural tube defects and syndromes such as epilepsy, schizophrenia, and mental retardation. This project will identify the molecular mechanisms regulating NEP stem cell activity and the birth of new neurons in the embryonic neocortex.
Exploiting The Cross Talk Between Tuft Cells And Group 2 Innate Lymphoid Cells For Tissue Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,162.00
Summary
The project investigates the cellular cross talk within the gastric mucosa between tuft cells, a rare epithelial cell type, and tissue-resident group 2 innate lymphoid cells (ILC2). The tuft cell/ILC2 axis is driven by the two cytokines interleukin (IL)-25 and IL-13 and is required for tissue homeostasis but turns pro-tumourigenic in the context of chronic inflammation. Our investigation will dissect the underlying mechanisms using a combination of mouse models, immunology and bioinformatics.
Stem cell to differentiation occurs in a bi-directional fashion. Dedifferentiation which allows specialized cells to become stem cells has been found to be important in both cancer and regeneration. In this proposal, we will investigate the metabolic reprogramming of neuronal dedifferentiation. The findings from this study will better inform us on how to specifically target tumours that arise from dedifferentiation.