PhD project but may also be considered for an Honours project
Biological trace elements, also known as trace minerals, or biometals include copper, zinc, iron, selenium and manganese. These and other biometals have essential roles in many areas of brain function including energy metabolism, transcription factor activity, antioxidant regulation and synaptic signalling. During ageing and brain disease, regulation of biometals is dramatically altered with changes to cellular and subcellular handling and localization. This leads to impairment of brain cell function, in both neurons and surrounding cell types (astroglia and microglia) and contributes to neuronal cell death in disorders such as Alzheimer’s, Parkinson’s and motor neuron diseases, as well as in lysosomal storage disorders such as Batten disease (childhood brain disorder). Our research has uncovered some of the processes involved in loss of biometal regulation and found this to be an early event in many disorders. We are also developing compounds that can help restore biometal stasis in the brain.
This project involves the investigation of new metal-based compounds as potential therapeutic or diagnostic agents for Alzheimer’s disease and other brain disorders. These compounds have unique properties including modulation of brain cell signalling, control of anti-oxidant function, and regulation of neuro-immune responses. The project examines the action of the compounds on a range of cell-types including animal and human neurons, astrocytes and/or microglia, and we aim to understand the molecular pathways that contribute to therapeutic action. Longer-term projects will involve the examination of the compounds as therapeutics in specific animal models of brain disease to determine if they are suitable for further therapeutic or diagnostic development towards the clinic.
The wet lab project will utilize a range of tools and techniques including brain cell culture, analysis of immune response (cytokine analysis), phagocytosis assays, anti-oxidant assays, X-ray analysis of biometal distribution and metalloproteomic studies on metal-protein interactions.