Research Projects
GREETING
[Coordinator (Research Director)]
Naoki Sugimoto
Director and Professor
Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University Technology (genome editing technology, CRISPR/Cas9) that edits disease-causing genes and permanently rewrites genetic information (nucleotide sequence) is an innovative technology with the potential to treat genetic diseases for which no cure exists. However, genome editing technology also carries a serious risk that new diseases may outbreak. Therefore, the development of new gene expression control technology by non-genome editing as well as improvement of existing genome editing technology is long awaited. Nucleic acids (DNA and RNA), as substances responsible for heredity, are thought to have a double helix structure. However, nucleic acids form non-canonical structure of nucleic acids such as triple helix and quadruple helix, depending on the surrounding environment, even with the same nucleotide sequence. Because the formation of non-canonical structure of nucleic acids inhibits biological reactions involved in gene expression, structural changes in nucleic acids in the cell can cause fluctuations in gene expression (Figure 1). Therefore, in this Core-to-Core Program, we will improve existing genome editing technologies by chemical methods based on the analysis of nucleic acid structure and stability, and elucidate the gene expression mechanism regulated by the structural change of nucleic acids in response to the intracellular environment (Condition Response Intra-Structure Transition Expressional Regulation: CRISTER). Furthermore, by regulating CRISTER, we aim to develop innovative methods to regulate the expression of disease genes by "non-"genome editing.
In order to facilitate these studies, a research group at the Institute for The Frontier Institute for Biomolecular Engineering Research (FIBER) of Konan University, which will serve as the core research center in Japan, domestic partner research groups, and overseas research groups (partner research cores) in five countries (UK, Slovenia, USA, India, Italy) with high expertise will work together to form the Nucleic Acid Chemistry CRISTER Control Consortium. In this consortium, top-level researchers who have led their respective fields of expertise, as well as mid-career and young researchers who will be the core of the next generation, will be stationed at each core research center to conduct international research and personnel exchanges, which will lead to rapidly develop research. In addition, we will also implement a young researcher training program for postdoctoral researchers and graduate students to acquire cutting-edge "nucleic acid chemistry" methods at core partner centers in each country within this consortium. Through these activities, we aim to form an international exchange center by fostering young researchers under the keyword of nucleic acid chemistry and strengthening the network among the young generation of researchers.
Figure 1. Non-canonical structures of nucleic acids and their roles
Naoki SugimotoDirector and Professor
Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University Technology (genome editing technology, CRISPR/Cas9) that edits disease-causing genes and permanently rewrites genetic information (nucleotide sequence) is an innovative technology with the potential to treat genetic diseases for which no cure exists. However, genome editing technology also carries a serious risk that new diseases may outbreak. Therefore, the development of new gene expression control technology by non-genome editing as well as improvement of existing genome editing technology is long awaited. Nucleic acids (DNA and RNA), as substances responsible for heredity, are thought to have a double helix structure. However, nucleic acids form non-canonical structure of nucleic acids such as triple helix and quadruple helix, depending on the surrounding environment, even with the same nucleotide sequence. Because the formation of non-canonical structure of nucleic acids inhibits biological reactions involved in gene expression, structural changes in nucleic acids in the cell can cause fluctuations in gene expression (Figure 1). Therefore, in this Core-to-Core Program, we will improve existing genome editing technologies by chemical methods based on the analysis of nucleic acid structure and stability, and elucidate the gene expression mechanism regulated by the structural change of nucleic acids in response to the intracellular environment (Condition Response Intra-Structure Transition Expressional Regulation: CRISTER). Furthermore, by regulating CRISTER, we aim to develop innovative methods to regulate the expression of disease genes by "non-"genome editing.
In order to facilitate these studies, a research group at the Institute for The Frontier Institute for Biomolecular Engineering Research (FIBER) of Konan University, which will serve as the core research center in Japan, domestic partner research groups, and overseas research groups (partner research cores) in five countries (UK, Slovenia, USA, India, Italy) with high expertise will work together to form the Nucleic Acid Chemistry CRISTER Control Consortium. In this consortium, top-level researchers who have led their respective fields of expertise, as well as mid-career and young researchers who will be the core of the next generation, will be stationed at each core research center to conduct international research and personnel exchanges, which will lead to rapidly develop research. In addition, we will also implement a young researcher training program for postdoctoral researchers and graduate students to acquire cutting-edge "nucleic acid chemistry" methods at core partner centers in each country within this consortium. Through these activities, we aim to form an international exchange center by fostering young researchers under the keyword of nucleic acid chemistry and strengthening the network among the young generation of researchers.
Figure 1. Non-canonical structures of nucleic acids and their roles
Outline of Core-to-Core Project
In this Core-to-Core Project, the coordinator on the Japanese side (Naoki Sugimoto, Konan University) will establish a nucleic acid chemistry CRISTER control consortium with researchers with world-class top-level achievements (overseas collaborating core centers). As part of our research plan (Figure 2), in our research to [explore] CRISTER, we will collaborate with the University of Reading, in UK, which has a proven track record in X-ray structural analysis, and a group at Slovenian NMR Centre in Slovenia, a world-class laboratory for NMR analysis. In the CRISTER [solve] research, we will collaborate with the group at Carnegie Mellon University in the United States and Calcutta University in India to develop and analyze artificial molecules that control nucleic acid structures. Additionally, in the study to [control] CRISTER, we will collaborate with the group at University of Padova in Italy, a renowned researcher in viral research, to evaluate the effectiveness of the artificial molecule at the cellular and individual level. Sugimoto et al. and their overseas collaborating core centers will feedback the results of their research to participating researchers in their home countries and develop genome editing and non-editing research for practical applications with domestic conducting computational science and clinical medicine research. In order to accelerate joint research with each core center, symposiums and international conferences will be held regularly to present the latest research results, especially for young researchers. In addition, with the aim of deepening exchanges among researchers, we will regularly organize short-term stays for researchers at each core center and hold research results' debriefing meetings. A program will also be offered to train young researchers from Japan and abroad with the aim of acquiring the techniques of state-of-the-art nucleic acid chemistry experiments. By assigning young and mid-career researchers who will lead the next generation as participating researchers and actively planning and executing this project, we will strengthen the collaboration with each core center and establish a continuous overseas collaboration system.
Figure 2. Research plan for this Core-to-Core project
Figure 2. Research plan for this Core-to-Core project