JAPANESE

Next Generation Research Incubator

Advanced Research of Infection and Immunity Based on Integrative Understanding of Host-Microbe Interactions

Detailed investigations of host–microbe interactions could yield new therapies against infectious agents and autoimmune diseases

The human body is made up of a staggering 30 trillion cells or so. But just as numerous, if not more so, are the trillions of microbial co-inhabitants that teem in and on us. These commensal bacteria and fungi are essential to our well-being, and a distortion in the microbial balance can trigger a wide range of disorders, from acne to obesity.

Only recently, however, have scientists come to appreciate just how critical this collection of microbiota is for determining human health and disease. They are also becoming excited about the prospect of how manipulating this microbial ecosystem could form the basis for the next generation of life-saving therapeutics.

Led by Mitsutoshi Yoneyama, researchers at the Medical Mycology Research Center have launched a comprehensive research effort to dissect the intricacies of host–microbe interactions in the skin, lung, intestine and spleen.

“Dysregulation of host–microbe interactions can give rise to a wide variety of human disorders, including opportunistic infections, allergies and autoimmune disease,” explains Yoneyama. “It is hence crucial to understand how hosts and commensal microbes communicate as a superorganism.”

Creating a superorganism is an apt metaphor for what Yoneyama is trying to achieve because, through the melding of minds from across Chiba and around the world, the center can make a far greater impact than any individual scientist working independently. At Chiba University, the investigators come from the Graduate School of Medicine and the Graduate School of Pharmaceutical Sciences, while external collaborators are based in the United States, Germany and elsewhere in Japan. These scholars, together with others from around the world, convene each November at the Medical Mycology Research Center for the annual Global Network Forum on Infection and Immunity.

Exploring host–microbe interactions

The team that Yoneyama has put together is roughly divided into four groups, each studying molecular interactions in different host–microbial systems. One, led by Shinobu Saijo and Yuumi Nakamura-Matsuoka, is focused on fungal infections in the skin of mice and humans; another, led by Koichi Hirose and Tomohiro Tamachi, is investigating the microbes — both good and bad — that reside in the respiratory tract. A third group, which includes Yoshiyuki Goto, is concentrating on the gut microbiome and how opportunistic intestinal infections gain a foothold; while the fourth, led by Akiko Takaya, is working on more basic mechanisms of immunological memory in response to microbial invaders.

“The results obtained from our projects will help efforts to create innovative new therapeutics against infectious diseases and will eventually lead to improvements in human health,” says Yoneyama, whose own research focuses on the mechanisms of innate antiviral immunity.

To assist all these research projects, investigators from each group have access to the Japanese government’s network of core facilities — a resource known as the Joint Usage/Research Center, which is staffed by specialized researchers and technicians who can run state-of-the-art experiments with fungi and other microbes. A bioinformatics unit at Chiba led by Hiroki Takahashi helps with computational analyses.