Environmental and Molecular Medicine
- Establishment of CRISPR-adaptation systems in mammalian cells
- Development of genome editing technologies by Class 1 CRISPR-Cas systems
- Homozygous mutation and phenotype analysis in human iPS cells by CRISPR systems
- Introduction of large-scale mutational genomic rearrangements in mammalian cells to study the impact on genome evolution and disease development
Establishment and applications of new CRISPR systems in vitro and in vivo of mammals
Bacteria and archaebacteria have an adaptive immune system that specifically recognizes and eliminates foreign invasion by organisms such as phages. The CRISPR system is used to introduce the genomic information of foreign organisms into a host genome (adaptation). When the same foreign organism intrudes again, the complementary genomic information captured in the host genome is used to alter and eliminate the foreign genomes (interference). CRISPR systems are classified into two different subtypes depending on the effector modules involved at the interference step. “Class 1” CRISPR systems are those that require multiple effector modules. Conventional CRISPR-associated genomic editing technologies make use of Class 2 CRISPR systems, mainly those derived from Streptococcus in which a single effector module Cas9 is involved.
We aim to recreate the Class 1 CRISPR adaptation system within mammalian cells that detects foreign microbial infection both in vitro and in vivo in mammals.
Other research goals involve the construction of highly efficient Class 1 CRISPR interference systems that work in vitro and in vivo.
In other work, conventional Cas9 technology is applied for chromosomal editing to selectively create homozygous alleles within human iPS cells for the analysis of unknown genes functions.
Moreover, in mammalian genomes including humans, the appearance of large-scale mutational genomic rearrangements such as deletions, duplications, inversions and translocations, are known to play important roles in various aspects of genome evolution (in particular, gene expression control) and the development of genomic diseases (in particular, malignant transformation). By making use of genome engineering technologies such as transposons, large-scale mutational genomic rearrangements can be artificially recreated at the cellular level. The development of new experimental systems will lead to better understanding of the effects of genomic rearrangements on genome evolution and disease development.
Through the exploration of the above-mentioned technologies, the ultimate goal is to contribute towards the development of new medical treatments and methods of diagnosis in the future.