Graduate School of Frontier Sciences, The University of Tokyo Department of
Integrated Biosciences

Three billion years is the time which evolution of life has spent. We cannot help being surprised by its exquisite beauty and resilience. However, someone is not satisfied with only the mystery of life. Yes, it is the nasty question like “So, how can you make it useful?”

We, the Laboratory of Applied Bioresources, are tackling head-on to “utilize the power of life”. We elucidate the mystery of life and make it applicable for food, health and welfare. We never ignore basic research, because we know we have to put our vast time and effort to understand what we really need. Life science of the people, by the people, and for the people. That is the Laboratory of Applied Bioresources.

Our Lab consists of 4 laboratories in National Agriculture and Food Research Organization, located in Tsukuba City.

The research theme of the Sezutsu Laboratory is "transgenic silkworm (genetically modified silkworm)". Silkworms produce silk threads, which is made of protein, to make cocoons. In other words, the silkworm is an ultra-efficient factory of protein production. The Sezutsu Laboratory has not only developed the most efficient technology in the world for making transgenic silkworms, but is developing applications of transgenic silkworms for producing pharmaceuticals such as human collagen and cancer diagnostics, instead of silk thread.

We have been the first laboratory that developed a method to produce transgenic/genome edited silkworm. It is still not easy to produce, so we are developing easier and more efficient methods. Furthermore, we are aiming at "insect design" to create even more amazing silkworms, "Super silkworms," by utilizing genome information. The Super silkworms can be a silkworm like giant “Mothra”, a silkworm that eats anything to grow, and a silkworm that is resistant to high temperatures and diseases.

Silkworms have been useful to humans for about 5,000 years by producing silk. Genetically modified silkworms can produce highly functional silk, which has never been produced before, and proteins that can be used as pharmaceutical ingredients instead of silk proteins, which can be of even greater benefit to people. We are collaborating with various companies, public research institutes, and universities to produce and commercialize a variety of highly functional silk and useful proteins. Some cosmetics and test reagents have already been commercialized, but we are working on further commercialization, as well as research and development of veterinary and human pharmaceuticals, for which there are many regulatory hurdles.

From the perspective of the SDGs, there is a shift from the use of petroleum-based fibers to the use of natural fibers, and silk is being reevaluated as a sustainable natural fiber, and increased production is expected. Therefore, we are trying to develop smart sericulture technology incorporating ICT technology, etc., to enable smart mass production. In addition to the silkworm, various insects such as Saturniid moths (called wild silkworm) and arthropods such as spiders also spit out threads. Their cocoons and threads have various characteristics such as strength, elongation, hardness, thickness, and color, and are an unused natural resource. We have begun to study the genes of these threads and incorporate them into silkworms to make them produce threads with these characteristics, and we are also trying to mass-produce insects other than silkworms by using genome editing to make them easier to keep.

Kikawada Lab is elucidating the desiccation tolerance mechanism in the sleeping chironomid, Polypedilum vanderplanki. Larvae of the insect has an extreme desiccation tolerance called "anhydrobiosis”, which refers to the ability to revive once it has completely dried up, as long as water is available. For most organisms, prolonged desiccation will result in death. This is mostly due to the irreversible denaturation of biomolecules such as lipids and proteins. On the other hand, the sleeping chironomid has acquired an ability of anhydrobiosis in the process of its evolution to prevent the denaturation even under desiccation. If the mechanisms could be applied, it will be possible to store valuable proteins in a dry state at room temperature without freezing. To realize such a future, we attempt to unravel the molecular mechanism of anhydrobiosis in the sleeping chironomid. (Kikawada Lab is the only laboratory in the world that investigates on anhydrobiosis in the sleeping chironomid.)

Anhydrobiosis is defined as a physiological state in which all metabolism has ceased in a dry state while maintaining the revivability. To elucidate the fascinating biological phenomenon, we have established a breeding system for the sleeping chironomid and has deciphered its genome. We have also confirmed that the cultured cell line (Pv11 cells) derived from the sleeping chironomids is able to exert anhydrobiosis. Currently, we are trying to get to the core of the molecular mechanism of anhydrobiosis in the sleeping chironomid using omics research and genome editing technology for Pv11 cells.

In Pv11 cells, proteins can be expressed from exogenous genes using transfection and stored in a dry state at room temperature for a long time. The components contained in the dried Pv11 cells should allow reproducing the dry preservation of proteins in a test tube. Because RNA accumulates in the dried cells without being degraded, it may contribute to the technology of long-term room temperature storage of RNAs as well as proteins. We have ambitions to overturn the common sense that biological materials have to be frozen or refrigerated for long-term storage.

The diversity of insects is remarkable even in the animal kingdom. Besides the sleeping chironomid, there are many other insects that occur in extreme environments where ordinary animals would die, such as the acid-tolerant chironomid that live in strongly acidic lakes with a pH of less than 2, and the petroleum fly that can inhabit tar pits filled with crude oil. We try to decipher the genomes of these insects and other invertebrates that dwell in extreme environments.

Dr. Hori’s laboratory is trying to detect and isolate agronomically important genes by using whole genome sequences and phenotypic data in over 40,000 accessions of rice landraces and cultivars (Oryza sativa L.). It has been over 15 years since the rice genome sequence was completely decoded in 2005. However, there are still more than 35,000 genes with unknown molecular functions. Isolation and functional analyses for these genes would be helpful understanding molecular basis controlling agronomic traits and developing novel rice cultivars showing superior agronomic performances.

Rice cultivars showed wide range of phenotypic variation for agronomically important traits such as grain quality, eating quality, yield, flowering time, disease resistance, seed dormancy and root architecture. We have isolated a lot of genes controlling these agronomically important traits from the natural variations of rice accessions. For an example, rice plants cannot accumulate enough storage proteins and starches in their grains under high temperature conditions. If we detect genes responsible for increasing starch and protein accumulations, we could easily develop novel rice cultivars showing high levels of climate resilience.

Rice grains are mainly used for cooked rice, wheat flours are used for making bread, cake and noodle, and corn starches are used for snacks and industrial materials. We collected several rice mutant lines for seed storage proteins and starches. Rice flour of these mutant lines made high quality of gluten-free rice breads. By using the mutant lines altering grain components, we are trying to develop novel rice cultivars that are available for food applications of other crops such as wheat and maize.

We collected single nucleotide polymorphisms (SNPs) distributed on the whole rice genome in rice landraces and cultivars. We also evaluated a lot of agronomic traits in the same rice accessions. Based on the SNP genotypes and phenotype information, genome-wide association study (GWAS) can detect novel genes for controlling agronomically important traits. Genomic selection (GS) procedure can build a prediction model for each agronomic trait and can estimate phenotype variations in progenies of the rice landraces and cultivars. We would like to shorten breeding periods for developing novel cultivars by less than half. These results can be used for genetic elucidation and breeding application in not only rice, but also other cereals, vegetables, and fruit tree crops.

Naito Lab is working on “salt tolerance of wild plants”. Current agriculture consumes lots of water, which actually excesses total rainfall. So we will be running out of fresh water, which we are drying up groundwater, rivers and lakes. So, we have come to a simple question: “If we do not have freshwater, why don’t we use sea water?” To realize this idea, however, we need plants that are tolerant to salt stress. This is why we are interested in wild plants that live in marine beach. These plants are extremely tolerant to salt stress, as they live facing to splashes of sea water. We are elucidating the mechanisms of such salt tolerance and how such mechanisms have evolved.

In addition to the above project, we are sequencing the whole genomes of plant genetic resources that are collected and stocked in our genebank. We are also working on a project to elucidate origins and histories of domesticate crops.

In the genus Vigna, relatives of azuki bean and cowpea, multiple species have independently acquired salt tolerance. Besides they are adapted to marine beach, their close relatives live in inland such as lake shores and river banks. In some cases the marine species have diverged from the inland population and acquired salt tolerance. In other cases, the inland populations have diverged from the marine population and lost salt tolerance. Such plants that are “genetically close but different in salt tolerance” are very good materials to perform comparative genomics and transcriptomics to understand genetic mechanisms that underlie the gain and loss of salt tolerance.

Research Center of Genetic Resources has a huge seed stock, with more than 200,000 accessions. Recently we have obtained a PromethION Sequencer from Oxford Nanopore Technologies to sequence as many accessions as possible. Well, to be honest, it costs money.

Many crops such as rice and wheat have originated in the continent and then have been transferred to Japan about 3,000 years ago or later. Azuki bean is, however, maybe an opposite. It has originated in Japan in late Jomon era, and has been transferred to Korean Peninsula and China. To test this hypothesis we are sequencing azuki bean and its wild ancestor, Yabutsuru-azuki, for population genomics study.