Professor Tsukita's research focuses on the role of tight junctions, which create the paracellular barrier in epithelial cell sheets and help organize the functions of biological systems. Epithelial cells attach to one another by tight junctions in a side-by-side fashion, creating sheets impermeable to water and solutes, including ions. Professor Tsukita seeks to elucidate the mechanisms underlying the structure and function of epithelial cell sheets through joint research with medical and scientific laboratories, with a focus on the tight junctional adhesion molecules, claudins, and their association with scaffolding and signaling molecules.
The tight junctions that create the paracellular barrier in epithelial cell sheets are critical for the functions of biological systems in multi-cellular organisms
Epithelial cells cover surfaces in the body, such as the lumen of the small intestine, and include the endothelial cells of blood vessels. Epithelial cells have the property of adhering to one another to form cell sheets. Cell sheets cover various organs in the body, the outer surface of the skin, and the inner surfaces of the small intestine and blood vessels.
How do epithelial cell sheets organize biological systems? Even when cells adhere to one another, gaps can lead to leaking and seeping. Without a mechanism for binding cells tightly to each other, fluids inside the body could leak out, and poisonous substances could enter the body. In addition to establishing the barrier between our body and the environment, epithelial cell sheets function to maintain microenvironments within the body. While epithelial cell sheets form the basic paracellular barrier between cells, some sheets, those of the small intestine, for example, function to selectively allow ions and other substances to pass through these paracellular barriers. The mechanism underlying this paracellular transport is my primary research interest.
The claudins are adhesive proteins that accumulate in the areas of adhesion between cells and construct tight junctions. These proteins also function as a platform for cellular structures and molecular signaling. I am analyzing these biological systems using an interdisciplinary approach. Recently, I have been especially interested in the apical membranes that exist on the outermost epithelial sheet layer and contain structures that are contiguous with the tight junctions.
Ignoring borders between medicine and science
The study of epithelial cells is strongly related to cancer research. Over 90% of all cancers arise in epithelial cells, and epithelial cells form the barrier between the inside of the body and the outside environment, placing them on the front line in protecting the body. In addition, the molecular mechanisms underlying the polarization of epithelial cells are being applied to interdisciplinary studies of cell types in a broad range of medical and scientific fields, such as neurology.
Cell differentiation along with cell polarization in epithelial cell sheets are important subjects in my research. In this respect, I am investigating the roles of ciliated epithelia and intestinal nutrient-absorbing epithelia. In the trachea and oviducts, multi-ciliated epithelial cells are specifically differentiated. Observing the movement of cilia in the trachea, we find that most of them bend in one direction in a synchronized way. The direction of ciliary bending is determined by the planar cell polarity of the epithelial cell sheet. My research examines the mechanisms by which the cell adhesion and cellular structures in this system are organized. In addition to my work on multi-ciliated epithelial cells, I am examining mechanisms related to the primary cilia and epithelial sheet polarity. Appendage structures are attached to the basal bodies at the base of the primary cilia, and these structures serve as the foundation for the polarization of apical membranes. An inability of the primary cilia to carry out this role is thought to lead to ciliary diseases, which have drawn the attention of many researchers in recent years.
I am carrying out my research without any concern for divisions between disciplines, such as that between medicine and science. Furthermore, in interdisciplinary studies involving engineering and informative science, our research includes computer analyses of cellular behavior and structural self-organization.
Expanding research through interdisciplinary work
I think that interdisciplinary research arises from personal contact and discussion among individuals. Researchers like me view issues from a biological standpoint, while others have views based on their respective specializations, such as physics or mathematics. From these interactions, we can discover new approaches within our own research, and interdisciplinary investigation broadens the scope of research as a whole.
For example, interdisciplinary research originating in biology can be extended into disease research. Approaching and analyzing the molecular processes underlying disease can lead to the development of new drugs and treatments.
Seeing things from the perspective of my students
Progress cannot be made in interdisciplinary research if those involved do not have the will to move forward. I personally ascribe to the importance of maintaining focus in an interdisciplinary research environment. When working with students, I try to see things from their perspective. It is critical when working with others to make sure you are being clearly understood to avoid miscommunication. Moreover, as I tell all my students, it is important to share, not only your knowledge, but also your enthusiasm. I think it is important to approach my work without being concerned about differences in age or experience. I expect the same of my students, and like to receive a lot of feedback from them during our work together.
I have also noticed that in recent years, students are more energetic and flexible in their approaches than in the past. It seems that they are becoming better at expressing their individuality. Today’s students also seem to express themselves proactively in their own ways. I am very happy to see these trends. I sincerely expect that new approaches in scientific research will emerge as students work together with openness and respect for one another. I am looking forward to working in this environment, in which I feel we can achieve new and heretofore unrealized scientific discoveries that will lead to better ways of living and thinking.