Laboratory of Computational Biology
Institute for Protein ResearchProfessor
Associate Professor

Kenji MIZUGUCHI
Kosuke HASHIMOTO
Specially Appointed Lecturer Reiko WATANABE
Assistant Professor
Chioko NAGAO

kenjikosuke.hashimoto
reiko-watanabec̲nagao

URL: https://mizuguchilab.org/Figure 2: Drug Design Based on Structural Information

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4-cell stage

Transcriptome analysis of early
human embryos
In early human embryos, transcription is
initiated at the 4-cell stage, which leads tothe production of new proteins and celldifferentiation. Recent studies have revealed
that a transcription factor called DUX4 isexpressed prior to zygotic genome activationand induces the expression of various genes
and retrotransposons. We investigate themechanism of activation of specificretrotransposons in early embryos byintegrating single-cell transcriptome datasetwith epigenetic datasets such as ATAC-Seq
and ChIP-Seq data. We also aim to identify
conserved and divergent elements of theretrotransposons among primates bycomparing human, macaque, and marmoset
embryos. Furthermore, we explore thetranscriptional activity of the retrotransposons
in a wide range of somatic cells, in whichsome of the retrotransposons might beadapted as regulatory elements.

Figure 1: High Performance Computer Systemegg cell

The increasing amounts ofexperimentally-determined protein
structures and interations have made it
possible to predict the structure, function,and interaction of proteins from theiramino acid sequence alone. We develop
novel comutaiontal methods using machinelearning and other techniques, but also
focus on the analysis of specific biologicalsystems, aiming to present hypotheses
testable by direct experimentation. For
example, we predicted the structure andbinding-sites of BIG3, a novel gene
exclusively overexpressed in breast cancer
cells. A peptide designed based on thisknowledge has been shown to block theinteractions between BIG3 and its partner
protein, and suppress the growth of breast
cancer cells both in vitro and in vivo.
Protein-protein intractions are attractive
targets both in drug discovery and basic
research, and remain one of our major
research themes.

Fertilized egg

Data integration for relating
molecular-level events to higherorder biological systems
A large amount of experimental data related
to various branches of life sciences are
already stored in public databases. However,many common issues need to be resolved
before they can be analyzed and utilized as“big data”. For example, information on
experimental conditions is not structured
sufficiently, making it difficult to select thenecessary data, and terminology and units areunstandardized. We are building databases
and developing technologies as a basis forconnecting molecular-level events to higherorder biological systems. For example, todevelop predictive models forpharmacokinetic parameters, we are building
an integrated database of data extracted fromseveral public data sources, which have been
manually curated by examining experimental
conditions and converting units appropriately.
Our TargetMine(https://targetmine.mizuguchilab.org) data
warehouse can assist discovery research in theearly stages of drug discovery, and stores datafrom numerous databases, concerning many
relationships such as those between genes anddiseases/phenotypes, and genes and tissues inwhich they are expressed. To integrate thosedata into an effective analysis platform, weare adopting unified terminologies andconcepts, and developing new analysis tools.

Understanding and predicting
protein-mediated interactions andmodeling biological responses

expression amount

We use computational methods tostudy biological systems anddiseases with applications to drug
discovery. As expectations for
artificial intelligence (AI) increase invarious fields, we recognize that theavailability of data organized in aform suitable for computer analysis
will have a significant impact on the
success or failure of AI
development. Our research isfocused on integrating a wide arrayof data, including genes, proteins,chemical compounds and diseases.
We are also developing methods topredict protein structure, function,and interaction, and applying thesemethods to specific data analysis.

Figure 3. retrotransposon expression in early embryos.
We aim to create an environment
where members of diverse
nationalities and backgrounds canwork together.

Institute for Protein Research, Osaka University
3-2 Yamadaoka, Suita, Osaka 565-0871, Japan
TEL: +81-6-6105-6961
FAX : +81-6-6105-6962
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