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DALL·E 2024-02-12 21.21.16 - Create an 18_9 image that combines the style of traditional J

Research

Our laboratory has strengths in technology development. We are proceeding with development by linking together "technology to measure minute and complex biological phenomena,'' "technology to organize and guide data to understanding,'' and "technology to create things from data.'' Here, we will introduce the details of technologies and ongoing projects.

01

Technology to measure minute and complex biological phenomena

​We are developing technology to analyze the genome and gene expression of microbes at the single cell level. To analyze diverse microbes in high throughput, manner, we have developed a new method that uses microfluidics. We have realized and commercialized the ability to acquire single cell genomes on a large scale from unknown environmental microbes**,***.

Hosokawa et al. (2017) Sci Rep.*

Chijiiwa et al. (2020) Microbiome**

Nishikawa et al. (2022) ISME Commun.***

Hosokawa et al. (2023) Biophys Rev

Single-cell genome analysis of microbes realized by SAG-gel (bit-MAP)
SMAGLinker integrates metagenomes and single cell genomes

Arikawa et al. (2021) Microbiome

02

Technology to organize data and lead to understanding

​We are developing a database and data processing workflow to improve, organize, and understand the acquired large-scale microbial genome data . We have developed a technology integrating single-cell genomes with metagenomes to improve genome integrity* and eliminate sequence errors**. Single-cell genomes are good at analyzing soil and ocean microbes***.

Arikawa et al. (2021) Microbiome*

Kogawa et al. (2018) Sci Rep**

Arikawa et al. (2023) CSBJ***

03

Technology to create materials from data

We can search for new enzyme genes from large-scale microbial single-cell genome data, and produce, evaluate, and modify proteins using genetic recombination technology*. We are currently working on producing bacteriolysis enzymes** that act against drug-resistant bacteria and plastic degrading enzymes***.

Hosokawa et al. (2023) J Biosci Bioeng*

Yoda et al. (2023) bioRxiv**

Mabashi-Asazuma et al. (2023) bioRxiv***

Searching for phage-derived molecules from genome information of oral bacteria

Hosokawa et al. (2023) J Biosci Bioeng

Technology

SAG-gel (bit-MAP®)

In metagenomics, which has been used to analyze microbes that are difficult to cultivate, it has been difficult to correlate which microbes have which genes. SAG-gel (bit-MAP®), which we have developed, is a technology that enables this association and examines complex microbial populations on a cell-by-cell basis. Microbes are physically encapsulated cell by cell in microcapsules, and DNA extraction and amplification from the microbes progresses inside each individual capsule, and the process of genome decoding progresses inside the small capsules. Since the information obtained is derived from a single cell, the genome can be determined without the need for complex computational processing, and the functions of microbes can be investigated. This method is now widely used for microbial genome analysis such as marine and soil bacteria and human intestinal bacteria.

Chijiiwa et al. (2020) Microbiome

SMAGLinker

Single-cell genomics has the characteristic of determining the genome sequence of each cell individually, making it possible to differentiate between closely related species and bacterial strains. However, the problem remains that single-cell genomics alone often results in incomplete genomes. In this method, data is obtained by performing metagenomics and single-cell genomics on the same sample, and then the metagenomic sequences are binned using the single-cell data as a reference, and sequences are assigned to each bacterium. Finally, by integrating both paired data, we combine the strengths of extensive metagenomic data and highly specific single-cell genomic data and output highly complete genome sequences with mutually complementary data. SMAGLinker is a series of operations constructed as a workflow.

Arikawa et al. (2021) Microbiome

https://github.com/kojiari/smaglinker

ccSAG

Sequence information obtained from single-cell genomics often contains biases and erroneous sequences. We have developed a new method called ccSAG. This is an analysis workflow for cleaning and assembling single-cell genome (SAG) data. This method combines multiple single SAGs from the same species or strains to create high-quality genomic data. Furthermore, this technique can also identify subtle genetic variations within the same microbial strain. Using this workflow, it is possible to obtain nearly complete genomes from uncultured microbes, allowing detailed analysis of their genetic diversity.

Kogawa et al. (2018) Sci. Rep.

https://gitlab.com/bitbiome/oss/ccsag2

Bacteria scRNA-seq

Single-cell RNA sequencing (scRNA-seq) is a technology that identifies particularly rare subpopulations of bacteria and reveals their diversity. We are proposing a new method for efficiently analyzing bacterial RNA. This method combines RamDA-seq, developed at RIKEN, and rRNA-derived cDNA removal using Cas9. This combination actually allowed us to detect over 1000 genes from a single E. coli cell. This makes it possible to efficiently obtain gene expression information at a lower cost than conventional methods and is expected to be used in gene expression analysis of various bacteria in the future.

Nishimura et al. (2023) J Biosci Bioeng

Projects

  1. Japan Science and Technology Agency: Emergent Research Support Program, Strategic control of microbiota designed from large-scale single-cell genomes, 2022 - 2024 Masahito Hosokawa
  2. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Challenging Research (Exploratory), Subpopulation Emergence from Heterogeneous Bacterial Communities at Single-Cell Resolution, June 30, 2023 - March 31, 2026 Masahito Hosokawa
  3. (Co-researcher) Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Academic Transformative Research (A) Development of Cytoplasmic Genome Editing and Gene Transfer Technology, April 2024 - March 2029 Shinichi Arimura, Miki Okuno, Fumiko Ishizuna, Hideki Takanashi, Masahito Hosokawa
  4. (Co-researcher) Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Academic Transformative Research (A) Genomic Control of Endosymbiotic Organelles: From Technological Innovation to Understanding and Application of Life Phenomena, April 2024 - March 2029 Shinichi Arimura, Masahito Hosokawa et al.
  5. (Co-investigator) Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Fundamental Research (A), Elucidation of the early adaptation process of bacterial cells to plasmids acquired by conjugative transfer, April 1, 2023 - March 31, 2028 Hideaki Nojiri, Masahito Hosokawa
  6. (Co-researcher) Japan Science and Technology Agency: Innovative GX Technology Creation Project (GteX), Development of advanced omics measurement and analysis platform to drive next-generation biomanufacturing, October 2023 - Takeshi Baba, Masahito Hosokawa et al.
  7. (Co-researcher) Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Basic Research (S), Comprehensive understanding of mucosal barrier construction and breakdown by intestinal bacteria, April 12, 2023 - March 31, 2028 Koji Hase, Reiko Shinzo, Masahito Hosokawa , Wakana Ohashi, Miki Matsuda
  8. (Co-researcher) Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Basic Research (A), Uncovering the limits of life and its adaptations through sub-sea life, April 1, 2023 - March 31, 2027 Yuki Morono, Motoo Ito, Masahito Hosokawa , Hideaki Kano, Akira Ijiri, Masahiko Sakaguchi
  9. (Co-researcher) Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Basic Research (B), Elucidation of the role of cell wall degrading ability of Streptococcus pneumoniae in pathogenesis and drug resistance acquisition, April 1, 2023 - March 31, 2027 Masaya Yamaguchi, Shigetada Kawabata, Michiko Sumitomo, Masahito Hosokawa , Hayato Yamashita

​​End

  1. NEDO Public-private young researcher discovery support project (startup problem solving support type) August 15, 2023 - February 29, 2024 Masahito Hosokawa

  2. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Scientific Research (A), New developments in the use of museum materials created by Shin Paleogenomics, April 5, 2021 - March 31, 2024 Takashi Kakuhari, Hiromi Matsumae, Masaaki Kanehara, Keiichi Motohashi, Kenji Okazaki, Shigeki Nakagome, Koji Ishitani, Masahito Hosokawa, Daisuke Waku

  3. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Fundamental Research (B), Development of a strategic resource utilization process for uncultured microorganisms based on single cell genome data, April 1, 2021 - March 31, 2024, Masahito Hosokawa, Yohei Nishikawa

  4. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Fundamental Research (C), Elucidation of molecular mechanisms of immunotherapy treatment resistance through microtissue multi-region sequencing, April 1, 2019 - March 31, 2022 Hayashi Okuo, Kazuya Takamochi, Masahito Hosokawa, Yoshiyuki Suehara, Tsuyoshi Saito

  5. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Scientific Research (S), Construction of an ultra-high-throughput screening platform for novel physiologically active substance producing strains, May 31, 2017 - March 31, 2022 Haruko Takeyama, Masahiro Ando, Masahito Hosokawa, Yukiyo Yutani

  6. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Challenging Research (Exploratory), Obtaining the full-length genome of uncultured microorganisms by non-amplified sequencing of single-cell genomes, June 28, 2019 - March 31, 2021 Day, Masahito Hosokawa

  7. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Fundamental Research (B), Integrated image and sequence analysis to elucidate the genome structure and transcriptional activity control within a single cell, April 1, 2018 - March 31, 2021, Masahito Hosokawa

  8. Japan Science and Technology Agency: Strategic Creative Research Promotion Project PRESTO Innovative technology platform for integrated single-cell analysis, creation of massively parallel genome analysis technology to reveal cellular diversity within tissues, October 2015 - March 2019, Masahito Hosokawa

  9. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Young Scientists (B), Development of single cell genome amplification method for difficult-to-cultivate microorganisms using micro reaction fields, April 1, 2014 - March 31, 2016, Masahito Hosokawa

  10. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Scientific Research (S), Deepening of microfluidic engineering and development of highly sensitive quantitative measurement of biomolecules, April 1, 2011 - March 31, 2016 Shuichi Shoko, Haruko Takeyama, Jun Mizuno, Satoshi Sekiguchi, Masahito Hosokawa, Mune-hyun Yoon, Miho Suzuki, Takeshi Fukuda, Takashi Funatsu, Naoya Takeda, Tetsushi Mori, Yoshikuni Edagawa

  11. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Fundamental Research (B), Development of a new digital counting method for the number of DNA molecules in a single cell, April 1, 2012 - March 31, 2015 Haruko Takeyama, Kyoko Yokota, Masahito Hosokawa

  12. Japan Society for the Promotion of Science: Grants-in-Aid for Scientific Research, Special Researcher Scholarship, Development of quantitative and qualitative evaluation method for circulating tumor cells by cell chromatography, 2011 - 2013, Masahito Hosokawa

  13. Japan Society for the Promotion of Science: Grant-in-Aid for Scientific Research, Special Researcher Grant, Development of comprehensive gene expression analysis method for single cells using porous carrier integrated substrate, 2009 - 2010, Masahito Hosokawa

DALL·E 2024-02-12 21.24.48 - Create an 18_9 image that captures the fusion of digital data
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