Conversing with cells at the fundamental level

At the fundamental level all biological systems operate through complex molecular interactions at the scale of single molecules. In order to observe or interact with the operation of cells and tissues at the fundamental level it is necessary to observe and interact at the molecular level. The scale of these interactions is best measured in billionths of a metre or the nanometre (nm).We want to enable biologists to be able to have two way interaction with living cells at this fundamental, molecular level.We propose a system of biotransducers operating at the nm scale. These will sense and control the chemical environment under the programmed control of the user.This requires three new technologies: nm-scale biotransducers, a system to deliver these biotransducers to the cellular environment and a way to speak to the biotransducers at the nanometre scale.In this proof of concept proposal we will tackle two of these: making biotransducers and talking to them. There is already proof of concept for delivering them (however, this is still a formidable challenge).The key challenge for the biotransducers is making a way to switch their behaviour so that they can be made to sense or influence their surroundings under the control of the user. We propose to combine newly available switchable agents with new research into nanosensor probes to achieve this.The key challenge for talking to the biotransducers is to communicate with them at the nanometre scale without disturbing the cells. Since this is beyond the resolution of conventional optical microscopes we propose to make a super-resolving optical nanoscope which exploits the switchable properties of the biotransducers to get nm resolution. This approach will allow real-time, wide-field and 3D addressing of the biotransducers.The technology to enable conversations with cells is hugely important and will revolutionise the life sciences - not only providing a way to see what is going on at the fundamental level but a way for the scientist to talk back and interact at the same level.