World Premier International Research Center Initiative (WPI) Executive Summary (For Final Evaluation)
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World Premier International Research Center Initiative (WPI) Executive Summary (for Final Evaluation) Host Institution Kyoto University Host Institution Head Juichi Yamagiwa Institute for Integrated Cell-Material Sciences Research Center Center Director Susumu Kitagawa (iCeMS) About filling out this form: This summary is to be based on the Center’s Progress Report and Progress Plan, with reference to the following items, prepare the summary within a space of up to 6 pages. A. Progress Report of the WPI Center I. Summary iCeMS, in its 10 years program, has always set out to establish a unique place in science, at the interface of fundamental cell biology and materials science. This means that a fundamental approach is taken to the way that cell biology and materials can be combined to become relevant to global issues such as disease or diet, energy or the environment. This was a truly ambitious since the two fields could not be more different. Cell biology is the study of an evolved state with a complexity that we attempt to unravel to understand life. Material science is a state that grows more complex by our leaps of inspiration. In the integration of such diverse philosophies of science, we hold the tantalizing prospect of generating a new interdisciplinary field. The WPI program at iCeMS was always about creating and spreading the creed of ‘Global Awareness, Lateral Thinking, Iconoclastic actions’. iCeMS has been an island of creative free thought in science and administration for the last 10 years, providing a catalyst for innovative change in the rest of Kyoto University’s administrative system. We must continue to preserve this creed so it becomes deeply embedded within Kyoto University and indeed throughout the fabric of Japanese Universities. Kyoto University had long considered the establishment of an overarching institute to capture the key precepts of iCeMS. In 2016 Kyoto University has successfully established the Institute for Advanced Study (IAS) under the leadership of Fields Medal winner Prof. Shigefumi Mori. The credibility of IAS was guaranteed by the inclusion of iCeMS to it as its flagship institute, and by securing the future participation of most of the current WPI-iCeMS senior PIs as well the very best of untenured young iCeMS researchers. iCeMS can look proudly on its achievements, from its status within Kyoto University, as the place where traditions can be set-aside and replaced with new rules reflecting an internationalized research administration. It can reflect on its creation of an English language research environment with a 30% international researcher, and twice the national average of female researchers. It can bask in a constantly high level of research success, and the foresight of inviting a future Nobel prize winner as part of its world-class cadre of researchers. It can glow at the media attention the institute has garnered domestically. However now, looking forward, iCeMS is active in making sure the rest of the world knows what Japanese science knows, and which the WPI committee has acknowledged; that it is a world premier institute. This last step, the missing piece, is actually lacking across the spectrum of Japanese academia. The biggest future priority for iCeMS is a successful systematic international communication of itself and WPI, Japanese Science’s flagship international research program. Host Institute -1 The Center name II. Items 1. Overall Image of Your Center At iCeMS, we gathered an exceptional collection of internationally known cell biologist, materials scientists and chemical biologist from Kyoto University, from Japan and from around the globe, who were equally motivated by this difficult but rewarding challenge. These eminent researchers were given the freedom to define, through their collaborations, the framework of what such a new interdisciplinary movement would like. Under the iCeMS leadership of Prof. Susumu Kitagawa, a world class leader in materials science, an equal dialogue was established between the key iCeMS field of cell biology and materials science to identify the core values of iCeMS in the last 10 years. This resulted bring focus to the natural process of developing iCeMS identity as "Materials for Cell Elucidation and Control". This encompasses a holistic interaction between materials and the three essential properties of cells and cell biology, Cell Communication, Nucleus Information and Membrane Compartments. 2. Research Activities Cell Communication, Nucleus Information and Membrane Compartments can be succinctly described in this way: (i) Nucleus Information: The nucleus memorizes and processes centralized information in the cell. We strive to elucidate the dynamics and mechanisms of chromatin organization and transcription regulation during cell differentiation as well as reprogramming. By doing so, we can develop synthetic functional molecules, including those with photoinducible properties, to visualize and manipulate nuclear information processing. (ii) Membrane Compartments: Cellular membrane compartments mediate condensation and selection: inward and outward signaling cascades, energy conversion, and exchange of matter. We seek to understand the molecular mechanisms of these meso-domain reactions to develop molecular technologies for manipulating membrane functions by external stimuli such as light, magnetic field and heat. (iii) Cell Communication: Differentiation of stem cells into multicellular tissues is regulated by the communication between cells alone and cells with materials. We seek to uncover underlying mechanisms and develop scaffolds by molecular scale design for the reconstruction of functional cell architectures such as brain, muscle and germline tissues. It is important to show that a combination of excellent researchers is more than the sum of its parts, in working for these goals. This has happened across the spectrum of iCeMS researchers, and to give some idea of that, we can say that • iCeMS has published 1439 peer reviewed papers. • 536 of these publications are considered the result of interdisciplinary collaboration. • One out of every five of these has been within a high impact publication, such as Science, Nature, Cell Reports or other publications with impact factor >10. Just a few of the high impact results can be mentioned here. (i) Nucleus Information: We now successfully control gene expression by interdisciplinary methods (combinations of biology, physics, and chemistry) to regulate cell fates. Collaborative research among iCeMS groups revealed that gene expression dynamics are important for the activity of transcription factors. For example, using optogenetics, we can effectively control the proliferation and differentiation of neural stem Host Institute -2 The Center name cells. In other situations, we successfully activate pluripotency genes in mouse fibroblasts using synthetic molecules, whilst another study creates in-vitro eggs from stem cells. (ii) Membrane Compartments: The collaboration among iCeMS researchers allows for the smooth transition from materials fabrications to cell biology investigations. The idea generated in iCeMS indeed stimulated chemists to produce a new material concept ‘cell-inspired materials’ and the Kitagawa group synthesized several porous coordination polymers (PCPs) with functions similar to compartmentalization concept Furthermore, newly synthesized photoactive PCPs that implement the light-triggered release of nitric oxide (NO) are being used to investigate and control the roles of NO as intracellular and intercellular signaling molecules, heralding a new chapter in gas biology. (iii) Cell Communication: Multidisciplinary collaboration among iCeMS and other scientists generated outstanding outcomes in manipulating cell fates and cell-material interactions. A combination of cell biology and material sciences revealed that the laminin fragment greatly improves human stem cell culture. Screening of chemical libraries and subsequent chemical synthesis identified small molecules that direct differentiation of pluripotent stem cells into cardiomyocytes and late-stage pancreatic β-cells. iCeMS collaborations also identified a molecule that promotes enhanced adhesion of cultured human cells. 3. Interdisciplinary Research Activities At iCeMS, we put together cell biologist and materials scientists to achieve fundamental discoveries in these three focus areas. However, this does not guarantee they will instantaneously find the common language to work together. iCeMS has encouraged this interaction through focused funding schemes, monthly gatherings, annual retreats and even simply through the action of proximal working spaces. For example a Cross-Disciplinary Research Task Force explored original and innovative collaborative projects integrating functional smart materials with living cells. Every month many researchers including PIs and young researchers join to present research updates and to explore new areas for collaboration. Indeed we have been rewarded by an enhanced degree of materials-biology collaborations over the past 10 years. Moreover, the researchers are encouraged to present their work in ways that are accessible to those outside of the their field, through the iCeMS Learning Lounge series. As seen in the figure, initially such interdisciplinary collaboration were sparse, but in recent years, through a persistent effort, iCeMS has demonstrated greater, and continuously improving levels of interdisciplinarity, which invariably finds its impact within high visibility