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KEIO SFC JOURNAL Vol.22 No.2 The Journey of Advanced Biosciences at SFC
published on 2023.03
The Journey of Advanced Biosciences at SFC
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Foreword
Download this article (PDF):SFCJ22-2-00.pdfKazuharu Arakawa (Professor, Graduate School of Media and Governance, Keio University)
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The Historical Evolution of Mathematical Modeling of Metabolism in the Human Red Blood Cell
Zachary B. Haiman (Graduate Research Assistant at Department of Bioengineering, University of California San Diego, La Jolla, CA) James T. Yurkovich (Visiting Scholar at Department of Bioengineering, University of California San Diego, La Jolla, CA / Chief Innovation Officer at Phenome Health, Seattle, WA) Bernhard O. Palsson (Y.C. Fung Endowed Chair and Professor at Department of Bioengineering, University of California San Diego, La Jolla, CA) During the last half century significant advances in metabolic modeling and whole-cell simulation using the human red blood cell as a model system were achieved. From initial studies chaining enzymes together as pathways, modeling frameworks for metabolic pathways were developed. Simulation software capable of modeling multiple biochemical and genetic processes facilitated the move toward cell-scale modeling and enabled complementary workflows linking omic data and computational studies for model-driven design. Here, we review selected milestones in the history of mathematical modeling of the human red blood cell.
Download this article (PDF): SFCJ22-2-01.pdf -
A Reflection on Two Decades of Metabolomic Innovations in Capillary Electrophoresis-Mass Spectrometry at the Institute for Advanced Biosciences, Keio University
Philip Britz-McKibbin (Professor, Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Canada) The Institute for Advanced Biosciences (IAB) at Keio University was first established in April 2001 to become a leading international metabolomics center for advancing integrated systems biology research. Unlike other metabolomic centers worldwide, IAB strategically focused on developing capillary electrophoresismass spectrometry (CE-MS) technology as their central instrumental platform for comprehensive analysis of polar/ionic metabolites in conjunction with bioinformatic tools for biomarker discovery and biochemical interpretation. In addition to hosting two International Metabolomics Society conferences, training young scientists and founding successful spin-off companies, IAB has contributed to high impact metabolomic studies as applied to clinical medicine, functional genomics and multiomic studies, cancer diagnostic testing, agriculture and food science, as well as epidemiology and population health. IAB has also fostered metabolomic partnerships with the local community, clinicians and industry as reflected by their involvement in a prospective study of community-dwelling residents from Tsuruoka City and assessment of the quality of foods produced from the Shonai area. IAB has also spearheaded numerous CE-MS based metabolomic research collaborations elsewhere across Japan and worldwide. This short review will strive to highlight key milestones spanning over 20 years of research innovations in CE-MS metabolomics technology brought forth under the leadership of Dr. Masaru Tomita.
Download this article (PDF): SFCJ22-2-02.pdf -
20 Years of the Minimal Cell’s Rise from Theory to Practice
Yo Suzuki（Assistant Professor, Synthetic Biology and Bioenergy Group, J. Craig Venter Institute） J. Craig Venter（Founder, Chairman, and Chief Executive Officer, J. Craig Venter Institute） In any discipline, simple systems are desirable for understanding the basic workings in the groups of systems they represent. In biology, cells are established as units for life, but even the simplest cells in nature are complex systems with uncharacterized functions beyond simply living. Making a minimal model cell in the laboratory was therefore contemplated and then achieved. Many pioneering efforts, including those at Keio University, shaped the process. This endeavor created the synthetic genomics field and a worldwide community to understand the cell and explore its applications in biotechnology and medicine.
Download this article (PDF): SFCJ22-2-03.pdf -
The Latest Trends in Thermogenic Adipose Tissues ―A Message from the Epicenter of Obesity Pandemic
Kosaku Shinoda (Assistant Professor, Department of Medicine Diabetes Research Center, Albert Einstein College of Medicine) Obesity is not only a problem of appearance, but also causes various lifethreatening diseases such as glucose intolerance, dyslipidemia, hypertension, coronary artery disease, and hepatic steatosis. Obesity is on the rise worldwide, and it has become a “pandemic” that cannot be addressed only by improving lifestyles. In response to the obesity pandemic, attention has focused on Brown Adipose Tissue (BAT), a special type of adipose tissue that has anti-obesity effects due to its high energy consumption capacity. Although BAT evolved as a cold resistance mechanism, recent clinical studies have demonstrated that it prevents obesity1), glucose intolerance2), dyslipidemia3), and coronary artery disease4). This paper presents the latest BAT research published in 2021-2022 in an omnibus format, and aims to decipher the mechanism of BAT growth and activation.
Download this article (PDF): SFCJ22-2-04.pdf -
Rational Design and Evaluation Methods of Microbial Metabolic System Based on Mathematical Models
Yoshihiro Toya (Associate Professor, Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University) Towards a sustainable society, bio-productions of useful chemicals using microbial metabolism are attracting attention. To increase the conversion efficiency of a substrate to a target chemical, rational engineering the metabolic system based on available information is important. Although there are many approaches in metabolic engineering, model-based approaches have been promising ways for enhancing the productivities. In this review, I summarized recent technical progresses and remarkable applications based on model-based methods for designing and evaluating the metabolic systems. Furthermore, I discuss future perspective of metabolic engineering for microbial bio-productions.
Download this article (PDF): SFCJ22-2-05.pdf -
Biosystems Revealed by Multi-Layered Omics Technology
Mio Iwasaki (Junior Associate Professor, Center for iPS Cell Research and Application, Kyoto University) There are multiple layers of omics information in living organisms: for example in humans, genomic information consisting of 46 chromosomes, epigenomic information consisting of acquired modifications to the genome, information on tens of thousands of transcripts transcribed from the genome (transcriptome), information on hundreds of thousands of proteins translated from the genome (proteome), and information on thousands of metabolites (metabolome). While conventional measurement and analysis methods could only analyze each of these layers individually, recent technological developments have made it possible to integrate omics analysis of other layers to understand biological phenomena. In this review, I focus on the proteome analysis technology, which has been the most difficult of the various omics analysis techniques and show examples of trans-omics research.
Download this article (PDF): SFCJ22-2-06.pdf -
Functions of the Non-Coding Genomic Regions
Yuka W. Iwasaki (Associate Professor, Department of Molecular Biology, Keio University School of Medicine) Small non-coding RNAs (miRNAs, siRNAs, and piRNAs) play critical roles in development, gene expression, and genome stability through their ability to perform RNA silencing. Small RNAs form effector complexes with Argonaute proteins and guide them to target genes to repress their functionality. Among the small RNAs, piRNAs function in gonads to regulate transposons. Transposons are universal components of eukaryotic genomes, and the mobility of these elements causes DNA double-strand breaks and insertional mutagenesis. Focusing on RNA silencing, possible functions of the non-coding genomic regions are discussed.
Download this article (PDF): SFCJ22-2-07.pdf -
Towards Industrialization of Protein Materials
Hiroyuki Nakamura (Team Manager, Spiber Inc. / Doactoral Program, Graduate School of Media and Governance, Keio University) Junichi Sugahara (Director and Executive Officer, Spiber Inc.) Living organisms utilize proteins as materials for various purposes like silk, spider silk, wool, hair and nails. Proteins composing these materials are named structural proteins, as distinguished from enzymes and antibodies. Spiber Inc. has been trying to industrialize protein materials since its establishment in 2007. In this report, we introduce structural proteins and our challenge for their industrialization.
Download this article (PDF): SFCJ22-2-08.pdf -
Creating the Future of the Region and Enterprise ―The Institute for Advanced Biosciences, Keio University as a Platform for New Collaboration, Interaction, and Human Resource Development
Akiko Sakai (Coordinator, Community-based Collaborative Project, Institute for Advanced Biosciences, Keio University) Keita Takagi (Senior Deputy Manager, Business Lab TSURUOKA, Strategic Business Design Department and Sustainability Group, Corporate Planning Department, Sompo Japan Insurance Inc.) The IAB Community-based Collaborative Project, which started in 2019, returns to the origin of collaboration between the region that gave birth to IAB and Keio University, while creating a foundation for synergistic relationships between developing and growing institutions, and regional institutions and resources. We are aiming to create a virtuous cycle of new development and activation while effectively cooperating with. From 2018, Major companies that have signed a comprehensive cooperation agreement with IAB dispatches employees to Tsuruoka City, and the “Corporate Innovator Development Project” has started in which employees who have moved to Tsuruoka City can freely engage in activities. This paper introduces the initiatives of these two projects and states that the IAB has become a new platform for collaboration, interaction, and human resource development.
Download this article (PDF): SFCJ22-2-09.pdf -
Tsuruoka Science Park General Incorporated Association
Yoko Yuzawa (Coordinator (URA), Institute for Advanced Biosciences, Keio University) “Tsuruoka Science Park” used to mean the 21.5ha development area in the northern part of Tsuruoka City. In April 2021, “Tsuruoka Science Park General Incorporated Association” was newly established and the name also represents an organization that facilitates growth of the community. We report on the background of the establishment of this association, the expected role, and the status of activities to date.
Download this article (PDF): SFCJ22-2-10.pdf -
Education Program for High School Students at the Institute for Advanced Biosciences, Keio University
Takashi Togashi (High School Student Education Charge, Institute for Advanced Biosciences, Keio University) Akiko Shiozawa (Public Relations Charge, Institute for Advanced Biosciences, Keio University) Science education programs for high school students are conducted at Institute for Advanced Biosciences for the purpose of regional revitalization. An overview of each educational program, its history and now are described.
Download this article (PDF): SFCJ22-2-11.pdf -
Research on the Anhydrobiosis Mechanisms in Tardigrades
Sae Tanaka (Specially Appointed Assistant Professor, National Institutes of Natural Sciences, Exploratory Research Center on Life and Living Systems) Kazuharu Arakawa (Professor, Graduate School of Media and Governance, Keio University / Specially Appointed Professor, National Institutes of Natural Sciences, Exploratory Research Center on Life and Living Systems) Some tardigrades can tolerate almost complete desiccation by entering an ametabolic dehydrated state, referred to as anhydrobiosis. Dehydrated tardigrades exhibit extreme tolerance against various physical stresses, such as high pressure and high doses of radiation. However, the molecular mechanism of anhydrobiosis remains largely unknown. So far, the genomes have been reported in multiple species and the functions of tardigrade-specific proteins have been analyzed in vitro and in human cells. In this review, we introduce the research in tardigrades and other anhydrobiotic organisms and discuss the future perspectives.
Download this article (PDF): SFCJ22-2-12.pdf -
The Past and Future of Metabolome Analysis
Akiyoshi Hirayama (Associate Professor, Graduate School of Media and Governance, Keio University) About 20 years have passed since metabolome analysis was first carried out as an earnest method of analysis. Initially, its technical suitability against other analytical methods was debated; however, metabolome analysis has gradually been implemented in various applied researches, such as the elucidation of disease mechanisms and discovery of biomarkers, steadily achieving significant results. In this review, I outline the metabolome analysis technology that has been developed at the Institute for Advanced Biosciences (IAB) and give an outlook on the technology that will be required in the future.
Download this article (PDF): SFCJ22-2-13.pdf -
Data-Driven Science Using Metabolome Analysis
Masahiro Sugimoto (Project Professor, Graduate School of Media and Governance, Keio University) Interactions of various cellular molecules result in a wide range of biological functions. Innovative development of omics technologies enables the comprehensive profiling of these molecules. In this review, the technical aspects of metabolomics that can simultaneously quantify hundreds of metabolites have been described. In addition to statistical analyses, mathematical modeling of the metabolic systems has been developed to understand the metabolomic data. Such modeling studies simulating the dynamic transition of metabolic pathways have also been reviewed.
Download this article (PDF): SFCJ22-2-14.pdf -
Contribution of Metabolomics Technology to Gut Microbiota Research
Shinji Fukuda (Project Professor, Graduate School of Media and Governance, Keio University / CEO, Metagen, Inc.) The human intestinal tract has a wide variety of gut microbiota, which interact with host cells to form a complex intestinal ecosystem. It is becoming clear that maintaining the homeostasis of the intestinal ecosystem contributes to the maintenance of human health. It has been reported that disruption of the intestinal ecosystem can lead to not only intestinal-related disorders such as inflammatory bowel disease and colorectal cancer, but also systemic diseases such as allergies and metabolic disorders. Metagenomic analysis, which comprehensively analyzes the genes of the gut microbiota, is the mainstream approach to understanding the interaction between the gut microbiota and host cells, but in addition to this, metabolome analysis, which comprehensively analyzes metabolites that reflect the function of the gut microbiota, plays a significant role in this research field. Furthermore, metabolome approaches that integrate data obtained from both analyses based on bioinformatics and mathematical analysis are beginning to elucidate the full extent of how the intestinal ecosystem influences host homeostasis and disease development. In this paper, I would like to introduce the contributions of metabolome technologies in the field of gut microbiota research and recent efforts toward a full understanding of the gut microbiota by metabologenomics.
Download this article (PDF): SFCJ22-2-15.pdf -
Japan-Specific Authorship Order for Corresponding Authors in International Medical Science Papers
Junko Murai (Project Associate Professor, Graduate School of Media and Governance, Keio University) In academic papers, a corresponding author is responsible for every process before and after publication. Hence, the corresponding author is esteemed as one of the highest contributors as well as the first author. Here, I compared the order of corresponding authors between Japanese author-originated papers and non-Japanese author-originated papers published in 2021 in Cancer Research or Cancer Science. The analyses revealed that Japanese author-originated papers have a 20-fold higher rate of the second author as corresponding author(s) than non-Japanese authororiginated papers.
Download this article (PDF): SFCJ22-2-16.pdf -
Community Health and Bio-Psycho-Social Model ―Suggestions from Karada-kan Project and Tsuruoka Metabolome Cohort Study
Miki Akiyama (Professor, Faculty of Environment and Information Studies, Keio University) Toru Takebayashi (Professor, Preventive Medicine and Public Health, Keio University School of Medicine) This article introduces two of our community-based research projects in Shonai region, one is “Karada-kan” started in 2006 and the other is “Tsuruoka Metabolomic Cohort Study” started in 2012. Then the article discusses the usefulness of the multilevel approach to community health. Both projects are working with the community and complementary for promoting health and wellbeing of the residents. Using the bio-psycho-social model, the article argues the significance of two projects of Institute for Advanced Biosciences in Tsuruoka City.
Download this article (PDF): SFCJ22-2-17.pdf -
Past, Present, and Future of Genome Modification in Escherichia coli
Hirotada Mori (Professor Emeritus, Nara Institute of Science and Technology (NAIST)) Escherichia coli K-12 is one of the most well-studied species of bacteria. This species, however, is much more difficult to modify by homologous recombination (HR) than other model microorganisms. Research on HR in E. coli led to a better understanding of the molecular mechanisms of HR, resulting in technical improvements and rapid progress in genome research, and allowing whole-genome mutagenesis and large-scale genome modifications. Developments using λ Red (exo, bet, and gam) and CRISPR-Cas have made E. coli as amenable to genome modification as other model microorganisms, such as Saccharomyces cerevisiae and Bacillus subtilis. This review describes the history of recombination research in E. coli, as well as improvements in techniques for genome modification by HR. This review also describes the results of large-scale genome modification of E. coli using these technologies, including DNA synthesis and assembly. In addition, this article reviews recent advances in genome modification, considers future directions, and describes problems associated with the creation of cells by design.
Download this article (PDF): SFCJ22-2-18.pdf -
A Streamlined Method to Produce Cells Possessing Synthesized Genomes
Mitsuhiro Itaya (Specially-Appointed Professor, Shinshu University / Former Professor, Faculty of Environment and Information Studies, Keio University) Giant DNA can be synthesized but its delivery protocol to desired cells has been required. Bacillus subtilis has been established as a platform to produce giant DNA. A delivery protocol was developed at the Institute for Advanced Biosciences by application-oriented use of conjugational transfer system. The established protocol enables accurate and efficient transmission of giant synthesized DNA to recipient B. subtilis cell. Furthermore, the similar protocol was applied to deliver DNA to B. natto. The B. natto strain however should lack restriction-modification genes, reminding us that the genes are one of inhibitory factors on conjugational transfer. This is a good reminder on manipulation of future industrial microbes that have never accepted giant DNA before.
Download this article (PDF):SFCJ22-2-19.pdf -
Tsuruoka Dadachamame News Letter ―RNA Research Aimed at the Functional RNA Group, Institute for Advanced Biosciences, Keio University
Akio Kanai (Professor, Graduate School of Media and Governance, Keio University) We started our RNA research at the Institute for Advanced Biosciences (IAB), Keio University in 2001. Our strategy of integrating Bioinformatics and Experimental Biology allowed us to contribute to the discovery of various functional non-coding RNAs. We have also systematically identified and characterized RNA-binding proteins and RNA-related enzymes. Furthermore, we attempted to systematize and discuss the evolution of these RNA-related molecules by looking at them through the three domains of life: Bacteria, Archaea, and Eukaryotes, plus viruses.
Download this article (PDF): SFCJ22-2-20.pdf -
Development of Metabolome Profiling Method and Application to Cancer Screening
Tomoyoshi Soga (Professor, Graduate School of Media and Governance, Keio University) Metabolites are final products of gene expression and thus the measurement of the level of all intracellular metabolites, metabolome, has expected to become a powerful tool not only for understanding fundamental research but also for providing solutions to problems facing humankind such as healthcare, food, global warming and power productions. We proposed a new metabolomic profiling method for the analysis of most of all charged metabolites by capillary electrophoresis mass spectrometry (CE-MS). Recently we further developed high-sensitive and high-throughput CE-MS method. This article introduces the development of the technology and its application to rapid screening of patients with colorectal cancer.
Download this article (PDF): SFCJ22-2-21.pdf -
Download this article (PDF): SFCJ22-2-22.pdf
Memory of Prof.Tomita
Mitsuru Miyata (CEO, Miyata Institute of Technologies, KK / CEO, Healthcare Innovation, KK)
【chapter 1 Advanced Biosciences】
【chapter 2 Bioscience Researches by SFC Graduates】
【chapter 3 Revional Revitalization from Tsuruoka】
【chapter 4 Bioscience Researches by IAB Faculties】
【chapter 5 Two Decades of Scientific Adventure at IAB】
【Column】
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DNA Metabarcoding Analysis of Long-Eared Owl Asio otus Pellets Reveals Small Animals as Its Prey
Takumi Shimizu (Doctoral Program, Graduate School of Media and Governance, Keio University) Haruki Natsukawa (Japan Society for the Promotion of Science Overseas Fellow) Hiroki Yuasa (Doctoral Program, Graduate School of Media and Governance, Keio University) Hiroki Kuroda (Professor, Faculty of Environment and Information Studies, Keio University) Tomohiro Ichinose (Professor, Faculty of Environment and Information Studies, Keio University) The feeding habits of apex predators such as raptors have a major influence on the local ecosystem, but their predation targets have been analyzed by visual observation that requires extremely proficient skills of taxonomic classification to identify small animals. Identifying prey animals at the species level reveals predator biology as well as important information for conserving predators, but it is difficult using conventional techniques. In this study, we aimed to clarify the diet of the longeared owl Asio otus by DNA metabarcoding of its pellets in the central region of Kanagawa Prefecture in Japan, using three types of universal primer sets. The results indicate that the long-eared owl feeds on various types of warm-blooded animals including birds, rodents and bats in winter. Our findings also demonstrate the high efficiency and reliability of DNA metabarcoding in the study of predator–prey relationship.
Download this article (PDF): SFCJ22-2-23.pdf -
Re-Construction of Belief and Imagination Through SNS ―Semi-Transparent Écriture Induced “Multi-Connectivization” of Acts and Coming Vagueness
Rakuki Ogawa (Fourth Year, Faculty of Policy Management, Keio University) In this article, we discuss the possibility of grasping SNS not as a mere communication tool, but as a domain with multi-connectivization. By finding a common denominator of “vagueness” in Umberto Eco’s Opera Aperta and Roland Barthes’ concept of “l’écriture neutre”, and through examining socially engaged art and a concept of Deleuze & Guattari’s “soit...soit”, we conclude that the nature attached to the language of SNS is “rhizomatic”. It is pointed out that this rhizomaticity is triggered by “multi-connectivization” of acts, and that this triggering is due to the vagueness of gazes that characterize the SNS.
Download this article (PDF): SFCJ22-2-24.pdf -
An Approach to Achieve Well-being in Schools ―Practice of Generative Pedagogy and SEL in Public High School
Wako Ishiguro (Founder of Non-profit organization Seishun-kichi) What kind of school prioritizes its students’ well-being and provides education on how to live a better life? This paper is a report of field work conducted at a public high school that combined Social Emotional Learning and Generative Pedagogy in order to find an ideal way of learning which brings out each student’s individuality. Through this way of learning, what kind of expressions and movements arose in students and learning creators? Utilizing the notion of the “Inside out”, we will present our findings on the conditions in which this kind of learning is possible through an analysis of student narratives collected during our field work.
Download this article (PDF): SFCJ22-2-25.pdf
