Hiroshi Abe

Development of chemistry-based synthetic methodology for genome scale DNA

Grant No.：JPMJCR18S1

Research Director

Hiroshi Abe

Collaborator

Kiyoshi Asai	Professor Graduate School of Frontier Sciences The University of Tokyo
Natsuhisa Oka	Associate Professor Faculty of Engineering Gifu University

Outline

We will develop chemistry-based synthetic methodologies for genome-scale DNA as follows; 1. Highly precise PCR, 2. Novel DNA assembly method , 3. Chemical ligation enabling construction of DNA containing repeat sequences, 4. Highly precise and efficient phosphoramidite chemistry, 5. New algorithm for designing DNA fragments suitable for these synthetic methods. We will establish precise and automatable synthetic methodology for genome-scale DNA by developing these core technologies.

Akihiro Ohkubo

Development of an innovative flow method for chemical synthesis of genomic DNAs

Grant No.：JPMJCR18S2

Research Director

Akihiro Ohkubo

Outline

In this research, we will carry out “Improvement of an efficient method for synthesis of long DNA oligomers”, “ Development of a high-throughput flow system for chemical synthesis of genomic DNAs” and “Evaluation of photosynthetic efficiency of cyanobacteria having modified genes of photosynthetic pigments” by using our DNA phosphoramidite method without base protection and techniques for preparation of a slide glass immobilizing porous glasses at high density.

Kunihiro Ohta

Development of minimum genome renovation technology using TAQing system

Grant No.：JPMJCR18S3

Research Director

Kunihiro Ohta

Outline

This research is aimed to develop a new technology to produce artificial cells of excellent traits by introducing the minimum genomic renovation. For this aim, genome-reformation technology called “TAQing system” will be employed to generate proto-artificial cells with various useful traits. The key information from sets of phenotype-genotype will be collected, and utilized for the design of minimal modifications to genome and synthesized huge DNA (extra genome) which enable expression of new traits in designed-artificial cells with the minimum genome renovation.

Yasuhiro Kazuki

Genome writing and application using human/mouse artificial chromosome

Grant No.：JPMJCR18S4

Research Director

Yasuhiro Kazuki

Collaborator

Junichiro Ohzeki	Project Assistant Professor The Exploratory Research Center on Life and Living Systems National Institutes of Natural Sciences
Teruhiko Suzuki	Chief Researcher Department of Basic Medical Science The Tokyo Metropolitan Institute of Medical Science
Kazuma Tomizuka	Professor School of Life Sciences Tokyo University of Pharmacy and Life Sciences
Eiji Mizutani	Associate Professor Faculty of Medicine University of Tsukiba

Outline

We have constructed a human artificial chromosome (HAC) and a mouse artificial chromosome (MAC) that can autonomously replicate and distribute in mammalian cells. Using the HAC/MAC technology, we have also succeeded the generation of transchromosomic mice with Mb-sized human gene cluster. In this research, we will perform the development of fundamental technologies to efficiently introduce Mb-sized synthetic DNA into target cells using the HAC/MAC technology, and develop the basic technologies for ‘the elucidation of operative principle of genome sequence’ and ‘the industrial and medical applications’.

Katsuhiko Shirahige

Innovative research for design and use of functional artificial chromosomes

Grant No.：JPMJCR18S5

Research Director

Katsuhiko Shirahige

Outline

In this research, we aim to understand how to design a very long piece of DNA in order to make it function as genetic information in human and other mammalian cells. Particularly, we investigate the mechanisms of gene regulation. We also develop a method to introduce a long DNA molecule into cells. Our research will enable us to establish the effective way to re-write human/mammalian genome, thereby facilitating research and development via synthetic biological approaches in medicine and animal husbandry.

Masayki Su’etsugu

Cell-free on-chip genome synthesis

Grant No.：JPMJCR18S6

Research Director

Masayki Su’etsugu

Outline

The genome synthesis so far relies on living host cells for large DNA cloning, and thus is labor intensive and time consuming. In this research, we will develop a cell-free on-chip technology for synthesis of artificial genomes. To achieve this goal, we use our original enzymatic tools for DNA assembly and DNA propagation. These tools will be integrated into micro-bioreactor to enable high-throughput and nanoscale synthesis of large DNA molecules. We will also develop methods for genome transplantation in bacteria, and thereby evaluate the function of the artificially synthesized genomes.

Asako Sugimoto

Genomic changes that drive evolution of reproductive modes

Grant No.：JPMJCR18S7

Research Director

Asako Sugimoto

Collaborator

Taisei Kikuchi	Professor Graduate School of Frontier Sciences The University of Tokyo
Kohta Yoshida	Specially-appointed Professor Brain Rsearch Institute Niigata University

Outline

The Phylum Nematoda contains a great diversity of species that vary in modes of reproduction (e.g., gonochorism, hermaphroditism, and parthenogenesis). In this research, we aim to identify genomic changes that drive evolution of reproductive modes in nematodes, by comparative and functional genomic analyses using multiple nematode species. We further aim to manipulate nematode genomes to artificially switch their reproductive modes.