Research Interests
Basic life science research is currently undergoing a major transformation.
Since life processes are carried out by various proteins encoded within genes performing various functions, many attempts have been made to know these life processes through understanding the functions of individual proteins within the gene. Due to the hypothesis that the functions of proteins are defined by their characteristic three-dimensional structures, attempts (with much effort) have been made to experimentally clarify the three-dimensional structures of these proteins.
However, there is a large gap between the functions of individual proteins and their biological processes. For example, autophagy, one of our laboratory’s research themes, is carried out by the cooperative function of dozens of Atg proteins, but even when the function of each Atg protein is clarified as a single molecule, the phenomenon of autophagy still cannot be understood. Understanding the function of individual Atg proteins, as single molecules, will not help in understanding the phenomenon of autophagy. It has become clear that it is important to understand the collective behavior of proteins in order to understand their biological processes. A typical example that defines this mechanism’s collective behavior is the phenomenon of “liquid-liquid phase separation (LLPS)” in vivo; and since its importance was pointed out in 2009, many biological phenomena, including autophagy, have been viewed and studied with the use of LLPS.
LLPS in living organisms is a phenomenon in which proteins, nucleic acids, and other biomolecules are hyper-assemble to form soft liquid-like condensates (called droplets or membrane-less organelles), which create a "zone" for specific functions in the cytoplasm, nucleoplasm, or even inside an organelle. Many cases have emerged in which the introduction of the LLPS concept has enabled a clear understanding of biological processes that had yet to be fully understood despite the numerous amount of research that had previously been done. Due to this revelation, all kinds of biological processes are being reviewed worldwide.
Furthermore, protein structure research is presently experiencing a shift in perspective. Until now, the determination of the three-dimensional structure of proteins had been done experimentally and laboriously using X-ray crystallography, cryo-electron microscopy, NMR, and other methods. Our group has also determined the 3D structures of dozens of Atg proteins using these methods over the past 20 years. However, since the release of the structure prediction program ‘AlphaFold2’ in 2021, it has become easy to predict protein structures with high accuracy based on amino acid sequence information alone, allowing researchers to access any protein structure at their convenience. This is as if many researchers (that where not structural biologists) had been studying protein functions while blindfolded, to then suddenly have their blindfolds removed and are now able to view the protein as they study them.
In this period of change, our laboratory aims to make clear various biological processes at the molecular level by simultaneously advancing the following research points.
(1) Understand the behavior of proteins as a group, by using the concept of liquid-liquid phase separation.
(2) Rationalize functional analysis by making full use of 3D structural information.
(3) Simplify and reproduce complex biological phenomena in vitro (reconstitution).
(4) Perform cell biological research using yeast and mammalian cells.
So far, we have focused our research on the mechanism of autophagy, an intracellular phenomenon, but we have also begun to branch into the mechanism of higher life phenomena such as "sleep." We enjoy conducting this research to better understand the various interestingly mysterious phenomena of life.