Research Interests

Our target : Molecular machine made of protein

There are many proteins in nature, which are principal components of our lives, having high molecular recognition ability and catalytic activity that are still hard to artificially imitate.

However, from the viewpoint of application, the natural protein does not always have the optimum properties, where we think is the real charm of protein engineering. This is why we are trying to create various proteins by rational design and molecular evolution technologies. Through the development and utilization of suitable methods, we are expecting to create proteins that can make stunt that native proteins cannot. These will become an indispensable tool in the research area called synthetic biology, which is getting attention at present. In other words, our object is to create a machine that normal engineers are making with steel and plastics, with proteins! Also, our dream is not making enjoyable toys but making gadgets (tools) that are useful in real life.

Especially, we have been focusing on the development of a new detection method (open-sandwich immunoassay, OS-IA) based on the antigen-dependent dimer formation of an antibody variable domains (Fv = VH and VL). We proudly develop OS-IA as a unique and also useful detection (and selection) principle that no other methods rely on. However, the stabilization of proteins by its ligand is considered a general phenomenon, and there is no wonder that the principle is generally applicable to other binding proteins.

Including others, some of the themes in progress are introduced as follows.

Current research themes (excerpt)

・Novel immunoassay approach based on the stabilization of an antibody variable region (OS-IA)
　- Sensitive noncompetitive detection system for small molecules such as environmental pollutants and peptides
　- Integration of OS-IA with microfluidics
　- Development of a selection method for high affinity antibodies that is suitable for OS-IA
　- Application to intracellular protein modification detection
　- Molecular evolution of proteins based on OS principle
　- New molecular imprinting technique using antibody fragments
　- Novel fluoroimmunoassay reagent Q-body based on antigen-dependent quench release

・Quenchbody (a powerful fluorescent biosensor)

・Construction methods for antibody-enzyme fusion proteins that does not require gene manipulation
　 - expression of fusion proteins using trans-splicing

・Antigen-dependent artificial allosteric enzyme

・Creation of alkaline phosphatase that has higher activity and thermostability than the wild-type enzyme

・Novel molecular interaction assay based on the functional complementation of mutant luciferases

・Controlling cellular functions by antibody-receptor chimera