I have been interested in the chemical analysis of biological regulations along time axis.  According to this selection, I have started the world-first proposal of "nanobiology" and organized the field with my collaborators in 1993. In this field, we have been working in finding and analyzing phenomena where the microscopic movements of molecules are directly reflected in physiology. By combining single-molecule techniques and nano-manipulation with molecular biology, we have clarified the existence of protein sliding along DNA with tracking a DNA groove, and found the regulation by sliding. We have proved that a fraction of initiating RNA polymerase is inactivated and this inactivation is an essential part of transcriptional regulation, which exemplified the cases that a sequence of chemically essential steps may be modified by branched and non-purposive reaction for regulation in vivo. The branched mechanism is the first example of utilizing protein conformation as a molecular memory in biological nano-machines.

  Our present challenges are determining the primary contribution of one-dimensional diffusion of proteins along DNA. This problem has its own depth in physics, and thus collaboration with theoretical physicist is essential.