Protein aggregation plays an important role in biology and is closely associated with a range of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. However, aggregation is not simply a transition from individual proteins to large fibrils. Instead, proteins can pass through a complex and dynamic range of conformational and oligomeric states, many of which are short-lived and difficult to observe using conventional bulk measurement techniques.

This project will explore the use of solid-state nanopores as label-free, single-molecule probes of protein aggregation. In nanopore sensing, individual molecules passing through a nanometre-sized pore produce characteristic changes in ionic current. These signals contain information about properties such as molecular size, shape, charge and conformation, providing an opportunity to investigate heterogeneous protein populations one molecule at a time.

Depending on the scope and level of the project, students may investigate different aspects of this problem, including nanopore fabrication and characterisation, protein translocation through nanoscale pores, time-resolved measurements of protein aggregation, optimisation of experimental conditions, and computational or machine-learning approaches for analysing large single-molecule datasets.

The broader goal is to understand how protein populations evolve during aggregation and how transient molecular states can be detected and distinguished. The project sits at the interface of nanotechnology, biophysics, materials science and data science, and will involve access to advanced nanopore fabrication and high-bandwidth single-molecule measurement capabilities at ANU.

An interest in experimental physics, nanotechnology, biophysics, materials science or data analysis. Previous biological experience is useful but not required.