Research project
High Resolution Imaging Using Transient Binders
- Start date: 1 September 2023
- End date: 31 August 2028
- Funder: Engineering and Physical Sciences Research Council (EPSRC)
- Value: £1,524,139
- Primary investigator: Dr. George Heath
To better understand the behaviour of any disease and to develop treatment options for it, we need to understand processes occurring on the single molecule level as well as the cellular and tissue levels. However, biomolecules are highly dynamic and have complex structures which are difficult to observe simultaneously. Biomolecules such as DNA and proteins interact with many other molecules to perform their biological function. Exploiting these interactions with molecules such as drugs, to block or enhance function can be used to treat or prevent diseases. However, few experimental techniques can capture this information at the relevant spatiotemporal scales. This proposal will develop Localization Atomic Force Microscopy (LAFM) methods to enable near atomic resolution imaging of single biomolecules interacting with binding partners. By localizing the height signals as small molecules transiently bind to DNA or proteins, the resolution of the LAFM method will be increased and enable imaging of where drugs bind, how long they bind for and their effects on how the biomolecule functions. Additionally, the combined development of automatic spectroscopy methods will enable the measurement of binding kinetics on the µs to seconds timescale. This combination of high spatial and temporal resolution will allow new insight into protein and DNA including drug interactions, molecular mechanisms of disease and surface properties, opening opportunities to identify new drug molecules or targets.
Publications and outputs
Open-source AFM Image Analysis Software: https://github.com/George-R-Heath/NanoLocz