Chemical Biology: "Treasure Hunting" and "Mystery Solving"

We suffer from various diseases. Since 1981, cancer has been the leading cause of death in Japan, with one in three people dying from the disease. With the aging of the population, the number of patients with neurodegenerative diseases is also increasing, with 1.5 million patients with Alzheimer's disease and over 100,000 with Parkinson's disease. There are still no effective treatments for these cancers and neurodegenerative diseases. Furthermore, many aspects of the mechanisms by which these diseases develop remain unknown. We are conducting research to develop treatments for cancer and neurodegenerative diseases and to elucidate the mechanisms of their onset.

So, where should we look for treatments for these diseases? We are searching among compounds produced by microorganisms. There are more than one million species of microorganisms on Earth, each producing compounds with diverse structures beyond human imagination. Some of these are used to treat various diseases, such as antibiotics for infectious diseases, drugs for hyperlipidemia, and immunosuppressants. Moreover, the antiparasitic drug developed by Nobel laureate Dr. Satoshi Ōmura was also originally a compound produced by a microorganism. Therefore, we believe that effective treatments for cancer and neurodegenerative diseases can be found among the products of microorganisms, which possess diverse structures and a wide range of activities.

Next, how do we search for compounds that could become therapeutic drugs?

To do this, we first need to build cell model systems for these diseases. We build these cell model systems by culturing cells under conditions that mimic the disease state, creating cells into which we have introduced mutant genes found in patients with cancer or neurodegenerative diseases, and more recently, using iPS cells derived from patients. We then apply compounds produced by microorganisms to these systems. We search for therapeutic candidate compounds by detecting changes in cell morphology, proliferation rate, and cell viability after treatment with the compounds. This is truly a "treasure hunt."

Next, we investigate the mechanism by which the discovered therapeutic candidate compounds exert their effects on the model cells for cancer or neurodegenerative diseases. To do this, we first identify which intracellular proteins the compound targets. Furthermore, by elucidating the function of that protein, for example by knocking it down, we can not only gain insights into the mechanisms underlying the disease but also understand why the drug is effective. This is truly "mystery solving."

In this way, we not only aim to treat diseases with compounds but also use compounds to elucidate life phenomena. This field of research is called chemical biology. The chemical biology of "treasure hunting" and "mystery solving" not only contributes significantly to medicine but is also very exciting as an academic discipline.