The pressing issue facing dementia research today is to understand the early changes in brain function leading to dementia. In this project we will investigate the role of early changes in naturally occurring stem cells obtained from the olfactory system of people who are either high risk for dementia, or in the early stages of disease. This will involve isolation of olfactory stem cells (OSCs) from the olfactory mucosa tissue collected from the nasal cavity. Nasal biopsy has been used to harvest olfactory mucosa tissues in basic and clinical research settings. Our collaborator, Prof Mackay-Sim (2017 Australian of the Year), has made many important discoveries regarding cellular abnormalities in neurological diseases, based on nasal biopsies collected from living human patients. Recent studies have identified unique gene signatures in the olfactory tissue obtained by biopsy from people with early stage Alzheimer’s disease. The importance of these genetic signatures is that they reflect ‘somatic’ (i.e. induced by the environment) rather than ‘germline’ (familial mutation) changes. This means that the changes in genetic information are directly associated with disease onset rather than a genetic mutation that someone is born with (which doesn’t provide us with information on disease onset or progression, especially in the majority of late-onset cases where no gene mutation is evident). The somatic signatures (known as ‘epigenetics’) provide critical information on disease form, stage, etc, especially when combined with common pathological markers such as amyloid and tau accumulation.
We are in a unique position to gain a deep understanding of the early genetic and protein changes that occur in initial stages of Alzheimer’s disease with the potential to provide a powerful diagnostic signature of early disease. The olfactory system contains naturally occurring multipotent stem cells, which can be grown into neurons and their supporting cells, the glia (e.g. astrocytes) in cell culture. This allows us to examine the genetic and protein changes occurring early in disease in the correct cell types that are affected in dementia (neurons and glia). This will provide unique information on disease processes that can only be obtained through examination of the correct cell types from dementia patients.
In this project nasal biopsy will be taken from the patients and the tissue used to generate olfactory stems cells, which will be differentiated into neurons and astrocyte-like cells of the brain. These cells will then be used for a range of analytical studies to understand the early changes that occur in neurons and glia of dementia patients or those at risk of dementia. This will provide us with a unique insight into the earliest pathological changes in brain cells derived from human dementia patients with the hope of identifying new biomarkers of disease and/or therapeutic targets.
- Aim 1: To collect olfactory mucosal tissue by nasal biopsy from people with early dementia or who are at-risk of dementia, and matched healthy controls
- Aim 2: To characterize the gene and protein expression of olfactory stem cells obtained from olfactory mucosa associated with dementia
- Aim 3: To investigate the multipotency of the olfactory stem cells and generate mature neuron and glial cell cultures
- Aim 4: To characterise pathological changes and gene/protein markers in differentiated neurons and glia grown from olfactory stem cells.
Techniques will include neural stem cell culture, molecular studies (i.e. RT-PCR), microscopy (confocal imaging), various biochemical assays (i.e. cytokine bead arrays) and protein analysis (western blot).
PhD project but may also be considered for an Honours project.