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.
The Role Of Membrane Phospholipids In Regenerative Axonal Fusion
Funder
National Health and Medical Research Council
Funding Amount
$571,950.00
Summary
Injuries to the nervous system can cause lifelong disabilities due to ineffective repair of the damaged nerve fibres. Our previous research has identified a highly efficient mechanism that occurs in nematode worms that allows severed nerves to fuse back together. We will now focus on understanding precisely how this mechanism works, and investigate its utility in repairing nerves that don’t normally utilise this repair mechanism.
Mechanisms Of PTEN Regulation By Ndfip1 And Their Biological Consequences For Neuron Survival During Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$686,640.00
Summary
We have discovered a new protein (Ndfip1) that protects brain cells from death after brain injury from trauma and stroke. We will investigate why this protein is activated only in some, but not in other, brain cells after injury. In this application, we will study the mechanisms behind neuron protection, and use this information to explore how to increase the number of brain cells activating Ndfip1.
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.
Emotionally traumatic experiences are well remembered and, in some instances, frequent reminders of these events can lead to the development of fear-related anxiety disorders such as phobia or post-traumatic stress disorder (PTSD). The experiments outlined in this proposal will examine how a novel epigenetic mechanism of gene regulation contributes to the transition from the retrieval of a fear memory to its inhibition through a process called extinction.
Nfib Regulates Glial Differentiation During Development And Disease Via Repression Of The Key Epigenetic Protein, Ezh2
Funder
National Health and Medical Research Council
Funding Amount
$572,912.00
Summary
Glial development is critical during development, and unrestrained proliferation of glial stem cells in the adult can lead to deadly brain cancers such as glioma. At present there is no cure for glioma and current treatments do not significantly delay tumour progression. Nfib is a transcription factor that may prevent tumour growth through cellular differentiation. We will investigate the role of Nfib during development and in the pathogenesis of glioma and its potential as a therapeutic target.
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.
How Does Iron Accumulation Affect Parkinson’s Disease And What Controls It?
Funder
National Health and Medical Research Council
Funding Amount
$545,517.00
Summary
Currently there is no cure for Parkinson's disease, and although we have a number of treatments to manage the disease there is an urgent need for a further understanding of the disease process. This proposal will investigate the critical role that iron plays in the cause of neuronal cell death that results in Parkinson's disease, and will investigate methods for regulating metal levels in the brain.
Aberrant Ependymal Development And The Formation Of Hydrocephalus
Funder
National Health and Medical Research Council
Funding Amount
$660,005.00
Summary
Foetal hydrocephalus is a prevalent neurodevelopmental condition associated with severe intellectual impairment. Breakdown of the ependymal cell layer, which acts as a barrier between brain tissue and the ventricular space, is a major cause of hydrocephalus. Despite the importance of these cells, we have little understanding of the molecular mechanisms that regulate their production. This project will identify critical signalling pathways governing the establishment of the ependymal layer.
The Role Of Store-operated Calcium Entry In Neuronal Development
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Defects in brain development can manifest in a range of disorders including autism and mental retardation. The highly complex, precise network that is our nervous system forms during development. Our work will determine the role of key proteins in guiding developing neurons. Understanding the function of such proteins will improve our ability to predict the outcome caused by mutations in these proteins, in the developing foetus.