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Purpose of Research

Control of pests is not only related to agricultural production, but also to greenery conservation, etc., and it also includes specific aspects associated with environmental technology. However, pest control methods using ordinary agricultural chemicals depend on antimicrobial and insecticidal activity, and therefore, they have a large environmental burden. Moreover, they do not necessarily conform to the requirements for social reassurance and safety. On the other hand, there are compounds that do not have antibiotic activity but can indirectly improve antimicrobial properties by creating a situation analogous to an immune response in plants. These are called resistance-inducing agents or plant activators. Since the implementation of disease control using these compounds involves low environmental impact and low risk of the appearance of resistant pathogens, it is gaining attention as an environmentally friendly method of disease control. Probenazole developed by Meiji Seika has shown its effectiveness in rice cultivation, and it generates nearly 10 billion yen annually. However, the activity of the resistance-inducing agent is indirect, and it is very difficult to evaluate the efficacy compared to fungicides, etc. Thus, it is difficult to select a candidate compound. To be specific, it is possible to know the status of resistance induction by monitoring the defense gene expression of plants, but usually it is necessary to extract proteins or messenger RNAs (mRNA), which is challenging, and constitutes a major barrier in the search for resistance-inducing agents. On the other hand, a disadvantage of these agents is the “phytotoxicity” that inhibits plant growth. This is a major barrier to efficient biomass production, which is why existing resistance-inducing agents are not necessarily widely used. An ideal resistance-inducing agent that does not inhibit biomass production is one that has a high disease control effect and “there is no phytotoxic damage such as growth inhibition etc.” However, the compounds that satisfy these requirements have not been observed thus far. The reason for this is that as previously described, the technology for searching for candidates for resistance-inducing agents is immature, making it impossible to search and evaluate many candidate substances. That is, an approach for identifying more candidate substances as resistance-inducing agents would be an important technical breakthrough. In this research, we will further improve the screening technology of resistance-inducing agents, etc. rationally and efficiently selected compounds with desirable characteristics, and develop a method capable of characterization, in addition to acquiring knowledge about the disease control effect of the substance and its mechanism of action at the field level. Furthermore, by utilizing unique organic synthesis technology, we will synthesize many low molecular weight compounds, acquire knowledge on their activities, harness this information towards the creation of new compounds by  targeted drug designs, and

finally, aim to “create a new type of plant activator that contributes to increasing the biomass.”

Research content / methods

Although attempts have been made to search for resistance-inducing agents or plant activators using gene expression and defense responses such as plant cell death etc. as indicators, they are all “endpoint assays,” and quantitative / qualitative selection indicators only provide data from one point of observation for each sample. On the other hand, the main feature of our assay system is the in-vivo super high-throughput screening method, which allows us to “continuously monitor” information from living plants. By exploiting this advantage to carry out screening of types and combinations, which are otherwise not possible with other research methods, we expect to discover and create unique compounds. If they are put to practical use, we expect sales of more than several hundred million yen per item, as “a material that is environmentally friendly and contributes to the maximization of biomass,” that would be a substitutable material for existing pesticides.

　The methodology and techniques used in this research are diverse. We expect there will be cooperation with the Department of Information Science on gene dynamic analysis, the Department of Material Science on the method of material application, etc., and with the Department of Ecology on the mechanism of action at the field-level. In the future, we expect that this work will develop into an even larger joint research project. In the previous project, this prospect succeeded, leading to the consignment of the (NEDO project: FY2016 Research expenses of 21,566K yen).

　As collaborative research within the university, we hope that this would lead to the development of practical researchers and engineers with advanced skills by directly reflecting the research and development process in　graduate school education.

　In addition, we started a university-originated venture (Yokohama Biotechnology Co., Ltd.) based on the screening technology developed through this project. We will create cutting-edge technology to support its technological superiority.