Department of Systems Biology

Institute of Life Science, Kurume University

How do the cellular molecular systems control behavior?
How do brain molecules determine when we sleep or are active?

Toward Understanding Biological Timing

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Our Research

Animal Sleep Analysis

Molecular biology, mouse genetics, physics (optics)

Is there a causal relationship between the identified factors in humans and sleep control?

Molecular Function Modification Methods:

  • Full-body KO by Triple-targeted CRISPR: Gene knockout using gRNA-1, gRNA-2, gRNA-3 via cytoplasmic injection (e.g., Cas9-expressing mouse or Cas9-carrying AAV).
  • Postnatal CRISPR-downregulation: Targeted gene downregulation after birth.
  • Overexpression of mutated molecules: Introducing mutated genes (e.g., PCamk2a mHcn2(G433D) WPRE SV40pA) via rAAVs for specific molecular manipulation.

Sleep & Wake Behavior Analysis Techniques:

  • Non-invasive respiration-based sleep phenotyping (Snappy Sleep Stager - SSS): High-throughput system for 396 mouse recordings per week, providing automated sleep staging based on respiratory signals. Learn more about SSS.
  • Electroencephalogram/Electromyogram (EEG/EMG) recordings: Invasive method for detailed brain wave (脳波) and muscle electrical activity (筋電) analysis to study sleep brain activity. Learn more about EEG/EMG.

Key Research Areas/Examples:

  • Discovery of molecular sleep-wake regulators through high-throughput genetics & phenotyping.
  • Respiration-based sleep phenotype screening of voltage-gated potassium channels by 3xgRNA-KO (Ballester Roig, Yamada et al submitted).
  • Sub-cellular specific manipulations showing post-synaptic PKA activity induces awake.
  • Research on HCN channels regulating sleep brain oscillations from excitatory neurons.

From Cell to Individual: Using cell-type specific perturbations to test the causal effects of biological time in organism.

Key Methodologies

Sleep & Wake Behavior Analysis

  • Non-invasive respiration-based sleep phenotyping: Snappy Sleep Stager (SSS)
  • Electroencephalogram/Electromyogram (EEG/EMG) recordings

Automated and high-throughput analysis of sleep and wake states in mice.

Efficient Genetics with Mouse

Advanced genetic manipulation techniques for studying molecular function in vivo.

  • Full-body KO by Triple-targeted CRISPR: Gene knockout using gRNA-1, gRNA-2, gRNA-3 via cytoplasmic injection (e.g., Cas9-expressing mouse or Cas9-carrying AAV).
  • Postnatal CRISPR-downregulation: Targeted gene downregulation after birth.
  • Overexpression of mutated molecules: Introducing mutated genes (e.g., PCamk2a mHcn2(G433D) WPRE SV40pA) via rAAVs for specific molecular manipulation.

Enabling precise control over gene expression and protein function in live models.

Our Team

Collaborations & Research Initiatives

We are proud to collaborate with leading institutions and researchers on various projects.

Ongoing Collaboration:
Department of Systems Pharmacology, The University of Tokyo

Key Collaborative Research Areas:

Human Sleep Measurement Group

Focus: Medicine (sleep, immunology), information science

What is the genetic and environmental basis of good sleep in humans living in the real world?

  • Development of a robust sleep detection method for abnormal sleep
  • Acceleration data analysis of 100,000 people
  • Estimation of the percentage of abnormal sleep
  • Measuring 50,000 sleep subjects
  • Sequencing EJS subjects
  • Human ethics review, human sleep research to identify sleep genes

Goal: Uncovering the fundamental factors controlling biological time and creating basic life science starting with humans.

Molecular Regulation Group

Focus: Biochemistry, structural biology, analytical chemistry

Is the transition of molecular state by multi-step phosphorylation a source of biological time?

  • Elucidation of qualitative control mechanisms
  • Search for perturbed compounds against molecular activity
  • Sub-cellular specific manipulations
  • Study of voltage-gated potassium channels (Kv) and HCN channels

Goal: Understand and manipulate the protein structure and its changes in biological time.

Publications

Contact & Access

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