Fellow 2012-13

Yann Robert Chemla


Understanding the Mechanism of Molecular Nanomachines with Combined Single-molecule Force Spectroscopy and Fluorescence Microscopy

Maintaining genomic integrity – faithfully copying the genetic code, repairing damage to the DNA – is the task of a group of specialized molecular nanomachines. These consist of tightly coordinated complexes of proteins that usually include one or more motor proteins (enzymes that convert chemical energy) as well as “accessory” proteins that help to package the complex or regulate motor activity.

Recently Professor Chemla’s laboratory developed a novel, hybrid instrument that combines high-resolution optical traps or “tweezers” with single-molecule fluorescence microscopy. The instrument allows them, for the first time, to follow the motion of a motor protein with high spatial resolution (of only a few ångstroms) while simultaneously monitoring its conformational state. During his Center appointment, Professor Chemla will direct two experiments using this instrument, with the goal of better understanding how two model motor proteins move along DNA: (a) investigate the conformational state of UvrD helicase, a motor protein with a critical role in maintaining genomic integrity in E. coli, and (b) probe the internal coordination of proteins that package the DNA of the T4 bacteriophage.

If successful, these experiments have the potential to address long-standing questions regarding the conformational dynamics and internal coordination exhibited by these proteins as they translocate along DNA. The results will also yield a better understanding generally of the molecular mechanism behind the operation (and pathology) of molecular nanomachines and gain insights into this fundamental component of cellular life.