My research program investigates the molecular & cellular pathways affected in neurodegeneration, using novel visualisation techniques, advanced molecular tools, and innovative approaches.
Some of the main research streams are:
- Mechanisms of neurodegeneration
- Glial interaction in the Central Nervous System
- Aggregation mechanisms in diseases such as MND
- Phase separation and condensation
- Drug delivery in the CNS
As part of the MND Research Centre at Macquarie University, a major focus in the lab is to better understand how the hallmark protein TDP-43 aggregates in disease and what drives it mislocalisation out of the nucleus into the cytoplasm. We have developed one of the first in-vivo models that allows the characterisation of TDP-43 aggregation in the zebrafish spinal cord. It is basically a live-stream into the nervous system. We utilise our platform to answer some fundamental questions that can’t currently be answered in other models.
For example, two key questions in the MND field are how disease aggregates mislocalise within a neuron and how they distribute through the CNS. My lab has developed several novel techniques (incl. laser ablation and live imaging protocols) to accurately monitor the degeneration process of motor neurons in the spinal cord and its impact on surrounding cells. These techniques provide the foundation for my ongoing research program: studying the mislocalisation of disease aggregates (intracellularly) and their fate after neuron degeneration (spread of disease).
Taken together, my research addresses a key limitation in this field by developing and validating an in vivo model and novel techniques that allow investigation of these processes.
We use a range of techniques and approaches to answer important research questions.
Some examples are:
My research mostly uses transgenic zebrafish, sometimes mice, and has a strong translational aspect with a clear goal of developing therapeutics for patients.
We utilise confocal microscopy techniques to visualise and conceptualise cell-cell interactions that are generally hidden to the human eye.
Microglia are the first immune responders in the central nervous system. They respond to injuries and physiological changes by disposing of material that is targeted for degradation.
We have developed innovative techniques and approaches to test and enhance drug delivery to the CNS and monitor their exchange.