Label-free mass imaging of single biomolecules in solution

The central theme of our research involves the application of optical label-free single molecule methodologies to studies of biomolecular interactions. Our approach rests on a simple optical microscope, where we have optimised signal collection and data analysis to the point where we can record images of singe, unlabelled biomolecules binding to a surface with extremely high quality. As a result, we can not only detect and image single molecules without the need for labels, but can use the achievable precision to accurately determine the molecular mass of each molecule. This capability enables completely new approaches in terms of the characterisation and quantification of molecular interactions. Current areas of interest include:

1. Protein self-assembly: We aim to elucidate the energetics and kinetics associated with oligomeric assemblies, such as those found in many protein complexes or viral capsids.

2. Nucleation: The goal is to unravel the molecular mechanisms behind the transition from individual protein molecules in solution to the formation of oligomeric seeds and subsequent growth into mesoscopic structures. These studies find applications for both physiological and pathological protein assembly

3. Mesoscopic dynamics: We want to understand the dynamics of mesoscopic biological structures, such as filaments, by monitoring the associated single molecule dynamics.

4. Protein-drug interactions: Our ability to precisely determine changes in molecules mass of biomolecules makes it ideal for the study of a variety of protein drug interactions without limitations associated sample heterogeneity.

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