Laboratory of Cell Engineering

About our research

Purpose of our research

All 46 human chromosomes are propagated accurately during cell proliferation. A large number of different functional proteins assemble on genomic DNA to make up the chromosomes. The "on/off" status of each of the 23,000 genes arranged on the 46 human chromosomes is modulated by these proteins. Thus, they play a crucial role in the development and differentiation processes through which various cellular characteristics are generated. Our research is focused on elucidating the mechanisms by which the functional structure of the chromosome is established and maintained through the interactions between chromosomal proteins and DNA.

Features of our research

We have cloned a long DNA sequence from a human centromere responsible for chromosome segregation, introduced the cloned DNA into cultured human cells and generated an artificial mini-chromosome (the 47th chromosome) with full centromere function. This Human Artificial Chromosome (HAC) has advantages for the dissection and reconstruction of molecular structures and mechanisms related to the chromosome, particularly centromere/kinetochore structure.

Expected fields of application

It is important to make full use of the enormous amount of human genomic information for further progress of the life and medical sciences. Our HAC is stably propagated as an extra mini-chromosome and can have multiple genes inserted. The chromosome can then control the on/off status of the inserted genes, either naturally or artificially. Our other goal is to develop HAC vector systems for gene delivery, protein production, and transgenic animal production.

Our research projects

1. Elucidation of Chromosome Functions.

We are investigating how proteins assemble on synthetic DNAs newly introduced into human and mouse cells, how the centromere/kinetochore and artificial chromosomes are assembled and maintained with the input DNAs through the cell proliferation process, and how the on/off status of the genes is affected by chromosomal structure.

2. Development of a gene delivery system using a self-removable HAC.

If an HAC containing active genes is capable of being transferred into any cell, but is also capable of being removed when no longer required, then the safety of gene therapy and iPS cell production will greatly improve because the risk of damaging the patient's own genomic DNA will be reduced. We have already developed a self-removable HAC by specifically suppressing the centromere activity on the HAC. We are now making further improvements to the self-removable HAC vector system and the HAC transfer methods used for gene delivery.

3. Development of transgenic animal production technology using a HAC system.

We have introduced multiple large human genes into a HAC and generated transgenic mice that retain the HAC with human genes through HAC transfer into ES cells. We would like to use these mice as models of human disease for basic medical research.

Publications