Olfactory stem cells for investigating the causes and progression of dementia

This project is suitable for a PhD or Honours student.

BACKGROUND

With no clinical success yet achieved from amyloid-targeting strategies, there is an urgent need to gain new insights and develop effective treatments for people who have dementia. New stem cell-based approaches have generated much excitement in dementia research with the potential to study patient-derived neurons and supporting cells. However, the commonly used ‘pluripotent’ stem cells are artificially generated and do not possess all needed cell types, which makes them unsuitable as tools to understand the disease process in the majority of late-onset (sporadic) cases of dementia.

Olfactory (nasal) tissue contains a unique population of naturally occurring stem cells that renew the nasal receptor neurons and supporting cells in the nose throughout life. These exceptional stem cells can be collected through a routine procedure with local anaesthetic and readily grown in a culture dish in a laboratory to produce neurons and other key brain cell types that accurately reflect the same types of brain cells that occur in the patient of origin. These cells provide a unique tool to study patient-specific disease processes and develop therapeutics for personalized dementia medicine.

OBJECTIVE

Our plan is to collect nasal tissue from people with dementia and from people who are at high risk for dementia (together with matching control samples). The olfactory stem cells will be grown in our lab and studied using a range of molecular approaches to provide unique insights into the early disease changes in a person’s brain cells. We are also attempting to grow brain ‘organoids’ from stem cells. These are ‘mini-brains’ that represent the 3-dimensional structure of a small part of a human brain and allow a much more accurate understanding of how brain cells work (or fail to work) in dementia. This will enable us to understand how brain cells are affected by dementia differently for each patient (i.e., derived neurons will retain patient-specific epigenetic markers) and will allow the screening of potential therapeutic drugs on an individual basis.