In our lab we are interested in the use and development of novel physical techniques to study biomolecular interactions including proteins, DNA and RNA at the level of single molecules. The advantages of single-molecule detection are many, apart from the fascination of looking at individual biomolecules at work, single-molecule techniques can measure intermediates and follow time-dependent pathways of chemical reactions and folding mechanisms that are difficult or impossible to synchronize at the ensemble level. Thus, single-molecule fluorescence techniques, in combination with advanced microscopes and manipulation methods, provide novel insights into how molecules and systems behave, having the advantage that spatial and temporal averaging is avoided, temporal synchronisation is not necessary and novel phenomena, which otherwise are averaged and remain hidden in ensembles, may be discovered.
Our lab is part of the School of Physics and Astronomy (http://www.st-andrews.ac.uk/physics/index.php)
and the Biomedical Science Research Complex (School of Biology) (http://www.st-andrews.ac.uk/bsrc/).
Our research applies elements of chemistry and physics to understand the complexity of biological systems and we are particularly interested in the following main areas:
1. Single-molecule Biophysics
2. Fighting pathogens: metabolite-sensing RNA-mediared gene-regulation processes
3. Protein misfolding and aggregation and its link to neurological disorders
4. Molecular machines involved in DNA and RNA processing
In our lab, students with physics and chemistry backgrounds have opportunities to apply their expertise in instrumentation, synthesis and analysis to interesting biological problems; and students with biological background are exposed to state-of-the-art or emerging physical technologies that can substantially expand their biological research capabilities.
Currently, we have two home-built single-molecule prism-type total internal reflection (TIR) microscopes to measure dynamics from submilliseconds to seconds; a single-molecule fluorescence correlation spectroscopy (FCS) microscope for faster dynamics and ensemble steady-state fluorescence, nanosecond time-resolved (TCSPC) spectroscopy and molecular biology facilities. We are currently developing single-molecule fluorescence with spectrograph capabilties for spectral information on individual molecules and further combining this with optical force manipulation methods.
We thank the funding bodies BBSRC, EPSRC, Royal Society, EMBO, The RS Macdonald Charitable Trust and donations for supporting our work. We thank also the The Wellcome Trust for funding specific projects and for awarding a funding strategic support to St Andrews to strengthen research at the interface of chemistry, biology, physics and medicine (ISSF scheme). These would typically be a precursor to more substantive funding. For those interested about ISSF, additional details may be found at this website: http://synergy.st-andrews.ac.uk/issf/