The Chemistry of Biological Defense in Nature

Among the substances that support our lives, biological functions, and daily activities, many organic molecules play crucial roles. Differences in the structure of these molecules lead to different functions and properties. In some cases, changes to molecular structures within the body can even be a cause of disease.

In our laboratory, our research focuses on the "shape and function" of molecules involved in biological defense, primarily those found in nature and within living organisms. "Shape" refers to the chemical structure, while "function" includes aspects such as affinity for other specific molecules, biological activity, and distribution and behavior within cells or the body. We are particularly interested in the group of molecules (many of which are derived from microorganisms) that trigger the initial activation of innate immunity, leading to the activation of the entire immune system, as well as the molecules that determine the balance of the adaptive immune system, typified by antibody-antigen reactions (Figure 1). To elucidate the roles played by our target molecules (compounds), we first perform organic chemical synthesis of natural compounds with immunomodulatory properties to obtain them in pure form. We then use these compounds to analyze their functions. Synthesis technology is applicable to the creation of all kinds of organic compounds—not only natural bioactive compounds but also those for drug discovery, electronic materials, and polymer materials—and is a technology that underpins modern human life.

Figure 2 shows examples of immunomodulatory compounds derived from the surfaces of natural microorganisms. Many of these have structures known as complex lipids or complex carbohydrates. Since it is theoretically possible to eliminate cancer by activating only the immune response against cancer cells if we can successfully regulate the immune system's balance by combining the functions of several active molecules, we are also conducting research aimed at designing and creating molecules that can selectively regulate the immune system.

The air we normally breathe contains countless microorganisms and compounds derived from them, along with dust and dirt. Many of these microorganisms are not necessarily pathogens that cause disease but are so-called commensal bacteria that are generally harmless. We unknowingly ingest substances derived from these bacteria as we breathe. Our research has clarified the structure of immunomodulatory molecules secreted by bacteria and has also revealed that these molecules are recognized by innate immune receptor proteins. Furthermore, much like the air, although we are not usually conscious of it, humans typically host over a hundred species of bacteria in their intestines (known as the gut microbiota), which are essential for a healthy life. While *E. coli* is famous for being discovered long ago, as it happens to be easy to culture, we also harbor many other difficult-to-culture bacteria in our intestines, maintaining what can be described as a symbiotic relationship.

In most cases, the phenomena described above are caused by changes that occur when molecules derived from microorganisms bind to or interact with human molecules (such as proteins on the cell surface). We also hope to elucidate the molecules that hold the key to this interplay between microorganisms and multicellular organisms, including humans. We believe that understanding the structure and properties of molecules based on "organic chemistry," and being able to view and deeply comprehend the phenomena around us through the lens of chemistry, is a privilege of living in our modern, scientifically advanced society. At the same time, it provides an opportunity to apply that knowledge for the benefit of humanity and society.