Abstract

A major advance in the physical sciences in the last two decades has been the development of quantitative methods to directly observe individual molecules in solution, attached to surfaces, in the membrane of live cells or more recently inside live cells. These single molecule fluorescence studies have now reached a stage where they can provide new insights into important biological and biomedical problems. After presenting the principles of these methods, he will give some examples from current research. He has used single molecule fluorescence to detect and characterise the low concentrations of soluble protein aggregates that play a key role in the initiation and spreading of Alzheimer’s disease. This provides new insights into how these aggregates damage neurons. He will then describe how fundamental science aimed at watching single molecules incorporating nucleotides into DNA gave rise to a new rapid method to sequence DNA that is now widely used.