The Yachie Laboratory1–7


1University of Tokyo RCAST
2University of Tokyo Department of Biological Science
3University of Tokyo AIS
4University of Tokyo GPES
5University of Tokyo PEAK
6Keio University IAB
7Keio University SFC

DNA Event Recording Biology

The Yachie Laboratory is a Synthetic and Systems Biology laboratory at the University of Tokyo°«s Research Center for Advanced Science and Technology (RCAST). While current omics and single-cell technologies have enabled measurements of high-resolution molecular snapshots of cells at a large scale, these technologies all require the destruction of samples at a time of observation and prevent us from analyzing dynamic changes in molecular profiles, phenotypes, and behaviors of individual cells in a complex system. Our group has been developing new technologies with the basic idea of "DNA event recording", in which large-scale genetic circuits are embedded in cells to record their environmental changes and high-resolution molecular profile history information in synthetic DNA sequences along with time. In this idea, high-resolution molecular profiles of cells can be obtained together with the cellular history information recorded in their individual "DNA tapes". By harnessing the concept of DNA barcodes and genome editing, we have been developing technologies to understand (1) the whole-body cell lineage of multi-cellular organisms, (2) molecular profile dynamics of cell clones in cancer progression and ES cell differentiation and (3) dynamic cellular protein interaction networks. We also develop new genome-editing enzymes as new DNA "writer" devices, DNA sequencing methods as DNA "reader" platforms, and DNA synthesis and genetic methods to realize high-capacity DNA "information storage" media.

Review articles on DNA event recording from our laboratory:

Masuyama M and Mori H et al. DNA barcodes evolve for high-resolution cell lineage tracing.
Current Opinion in Chemical Biology 52, 63-71 (2019) PDF

Ishiguro S et al. DNA event recorders send past information of cells to the time of observation.
Current Opinion in Chemical Biology 52, 54-62 (2019) PDF

Our major research topics include:

Development of new genome editing technologies
Cell lineage tracing of development and cancer cell progression
High-throughput screening of protein interactions

Genome Editing Projects


The recent understanding of CRISPR systems has triggered the dramatic development of genome editing technologies. In addition to double-stranded DNA cleavage and nicking, catalytically inactivated Cas9 mutants anchored to functional protein and RNA domains have enabled flexible regulation of gene transcriptions and epigenetic modifications at nearly any sequence complementary to the designed guide RNA. Notably, targeted DNA deamination strategies coupled with CRISPR systems enable targeted C•G to T•A and A•T to G•C modifications. This base editing approach allows direct genomic programming to create more stringent and complex cellular circuits compared to the conventional transcriptional induction systems. As basic techniques continue to enhance various research projects in our group, we are developing new base editors and new frameworks for genetics.

Nishida K et al. Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems.
Science 353, aaf8729 (2016) PDF

Sakata RC, Ishiguro S, Mori H et al. A single CRISPR base editor to induce simultaneous C-to-T and A-to-G mutations. bioRxiv 729269 (2019) PDF

Cell Lineage Tracing Projects

Development of any multicellular organism starts from a single fertilized egg. Individuals and organs are formed through cell divisions and differentiation where a large number of cells and their cellular pathways crosstalk. Based on a belief that a complete information of the cell lineaging pathways to organs and functional cells could be a strong backbone for developmental biology, we are developing a high-resolution cell lineage tracing method using DNA barcodes, genome editing, and single cell technologies, aiming to capture the whole body cell lineage of mammalian development (mammalian reference cell lineage) at nearly single cell division resolution.

Interactome Projects


Cancers and many other human diseases are not the product of defects in a few genes, proteins or simple pathways. Instead, they involve a complex web of molecular interactions that are dynamically regulated. Recent studies have demonstrated that the projection of genomic mutations to a reference cellular regulatory network could enhance the performance of disease phenotype prediction and that disease mutations alter more functional protein interactions than the other mutations. Therefore, conditional protein interactome information for different proteoforms (splicing variants and modifications), mutations, individuals and environments would deepen our understanding of collapses in functional networks and enable high precision prediction of disease phenotypes. However, such screening is difficult due to the combinatorial explosion in a number of experiments. Using DNA barcodes, barcode fusion concatenating different information and next-generation DNA sequencing, we are developing experimental frameworks that enable high-throughput screening methods of conditional protein interactions.

Yachie N and Petsalaki E et al. Pooled-matrix protein interaction screens using Barcode Fusion Genetics.
Molecular Systems Biology 12, 863 (2016) PDF

Bioinformatics Projects

Our group has various bioinformatics projects which range from supporting experimental projects by producing new types of experimental datasets, establishing new data analysis methods as well as other independent studies in bioinformatics. Our topics include data analysis of DNA barcodes and genome editing spectra, development of a parallel distributed computing method to reconstruct large cell and evolutionary lineages and discovery and analysis of structured and patterned DNA sequence elements in large genomic resources.

Mori H et al. Fast and global detection of periodic sequence repeats in large genomic resources.
Nucleic Acids Research 47, e8 (2019) PDF

Other research topics in our group include laboratory automation, DNA data storage and in vitro DNA computing using genome editing.

Yachie N, Robotic Biology Consortium & Natsume T. Robotic crowd biology with Maholo LabDroids.
Nature Biotechnology 35, 310 (2017) PDF

Positions Available

We are seeking creative and talented postdocs and students.
Please see here if you are interested in joining us.