Developing next-generation technology touching life physics tools to tackle debilitating infections and cancers

Our knowledge of many debilitating human diseases is limited by technology: conventional approaches fail to render the quantitative details needed to address key mechanistic questions. This project will develop new biophysics tools for molecular observation in live cells to aid understanding of two diseases of high biomedical importance - (i) Determining roles of a key haematopoietic cytokine receptor, MPL, which interacts with ‘oncogenes’ in rare blood cancers; (ii) Investigating the assembly/disruption of a druggable unique protein structure in protozoan parasites that causes sleeping sickness in humans:

1. Develop new microfluidics for high-throughput immobilization and optical imaging of cells, facilitating rapid exchange of cell microenvironments, screening of cell types/states and other biophysics investigations including genetics profiling.

2. Design and construct optical instrumentation to enable rapid tracking of labelled proteins in cells to nanoscale precision in 3D and improve the time scale of sampling to sub-millisecond levels to probe rapid molecular conformational dynamics.

3. Develop optical tools to determine cell physiology using novel probes for ratiometric imaging and Förster resonance energy transfer (FRET) to quantify precise pH, ionic strength, membrane voltage, viscosity, and molecular crowding.

4. Develop new computational methods of machine learning/AI, principal component analysis and Hidden Markov Modelling.