Nanoscopy of Dynamics in the Living Cell.

Dramatic advances in several physics-driven laboratories have established the principle of super-resolution optical imaging. Major improvements in spatial and temporal resolution are sorely needed for the technology to be useful to answer major biological questions. We propose a bold multi-disciplinary program to drive the technology forward with biological applications that demand dynamic visualization on the nanoscale in the belief that step-change technology development cannot effectively e volve without motivation and pull from those who need the applications the most. Leveraging major investments made by Yale, we have assembled a multi-disciplinary team of engineers, physicists, and cell biologists from the Gurdon Institute, the Cell Biology Department at Yale, the LMB at Cambridge, and Oxford University which over five years will develop a new generation of microscopes and probes capable of multi-color dynamic imaging deep in live cells with spatial resolution <50 nm in all d imensions which are to be sited in Cambridge and New Haven and made broadly available. The biological test bed to lead the technology is the dynamics of the secretory pathway, chosen because this difficult problem has resisted conventional optical solutions due to the close proximity of the substituent membranes. Optical nanoscopy impacts four of the Trust s major challenges.