Single Molecule Biophysics

Dr Liming Ying, Group Leader

Schematic of the combination of single molecule manipulation with single molecule imaging. Fluorescence-tagged ligand molecules may be delivered to the living cell surface using a nanopipette controlled by the scanning ion-conductance microscopy. The motion of ligand bound receptors can then be tracked by multi-colour single molecule imaging

The key processes of life occur in the noisy and far from equilibrium cellular environment, which is characterised by heterogeneity and stochastic fluctuation. To unravel this complexity, biology requires new physical concepts and methodologies. One promising approach is to measure the properties and dynamics of biological molecules, macromolecular machines, and cellular properties at the single molecule level. Single molecule approaches have the advantages of avoiding ensemble averaging, observing transient intermediates and heterogeneity (both static and dynamic), and they have started revolutionising the way many biological questions are addressed. Our group is interested in the development and applications of single molecule methodologies, in particular novel fluorescence imaging methods, to monitor the behaviour and properties of individual biological molecules, molecular complexes and molecular machines, in vitro and in living cells. We are currently working in the following specific areas:

Selected Publications

Huang F; Ying LM; Fersht AR. (22 Sep 2009). Direct observation of barrier-limited folding of BBL by single-molecule fluorescence resonance energy transfer. P NATL ACAD SCI USA. 106:16239-16244.

White SS; Balasubramanian S; Klenerman D; Ying LM. (2006). A simple nanomixer for single-molecule kinetics measurements. ANGEW CHEM INT EDIT. 45:7540-7543.

Ying LM; Green JJ; Li HT; Klenerman D; Balasubramanian S. (9 Dec 2003). Studies on the structure and dynamics of the human telomeric G quadruplex by single-molecule fluorescence resonance energy transfer. P NATL ACAD SCI USA. 100:14629-14634.