ringworm, when analyzing a factor that is thought to be involved in pathogenicity, a
mutant strain (gene-disrupted strain) is created in which gene encoding the factor is
artificially deleted. Then, a comparative analysis is performed with the wild-type
strain. However, creating such a gene-disrupted strain of Trichophyton is not easy.
No factor has been experimentally shown to be pathogenic, and no etiological factor
has been identified. This is the major reason underlying the inability to establish
treatment methods (Yamada et al., 2009).
3.2 Features of New Technology and Comparison
with Conventional Technology
Yamada et al. isolated a Ku80 ortholog of T. mentagrophytes and produced a Ku80
disruption mutant using targeted gene disruption. The Ku80 mutant showed a high
frequency of target gene disruption at two independent chromosomal loci, but no
phenotypic changes were seen. Therefore, these mutants have great potential for
large-scale molecular genetic studies of dermatophytes including T. mentagrophytes.
With conventional technology, the homologous recombination frequency that
occurs between the target gene and the transfer vector is extremely low, and gene
disruption and transfer are difficult in ringworm, so analyzing gene function was
virtually impossible. The development of a gene-disrupted ringworm (Tmku80) has
allowed the introduction of a new gene in ringworm. This enabled analysis of
resistance to virulence factors and antifungal drugs (Yamada, Yamada, et al., 2014).
4 Other Issues for the Commercialization (Practical
Application Process)
Currently, stable gene disruption and gene insertion are possible for ringworm.
However, the method has not been commercialized because the following points
need to be resolved ((1)–(3)). Discovery and selection of target molecules by
promoting basic research for practical application are needed. Table 1 shows the
Table 1 Historical background from the basic research to the application stage
History of industry–academia collaboration
1994–2000 Joint research with Toyobo Gene Analysis
1995–2000 Adopted by the New Energy and Industrial Technology Development Organization
Commission (Proposal Open Call/Advanced Research and Development Project)
1998–2000 Japan Space Forum selected for public ground research on utilization of space
environment in 1998
2007–
Japan Aerospace Exploration Agency joint research on microbiota in the space station
2012–
Joint research with World Geno-matrix
2015–
Joint research with Airy Technology Co., Ltd.
Realities and Challenges of Bridging Research in Japan
143
mutant strain (gene-disrupted strain) is created in which gene encoding the factor is
artificially deleted. Then, a comparative analysis is performed with the wild-type
strain. However, creating such a gene-disrupted strain of Trichophyton is not easy.
No factor has been experimentally shown to be pathogenic, and no etiological factor
has been identified. This is the major reason underlying the inability to establish
treatment methods (Yamada et al., 2009).
3.2 Features of New Technology and Comparison
with Conventional Technology
Yamada et al. isolated a Ku80 ortholog of T. mentagrophytes and produced a Ku80
disruption mutant using targeted gene disruption. The Ku80 mutant showed a high
frequency of target gene disruption at two independent chromosomal loci, but no
phenotypic changes were seen. Therefore, these mutants have great potential for
large-scale molecular genetic studies of dermatophytes including T. mentagrophytes.
With conventional technology, the homologous recombination frequency that
occurs between the target gene and the transfer vector is extremely low, and gene
disruption and transfer are difficult in ringworm, so analyzing gene function was
virtually impossible. The development of a gene-disrupted ringworm (Tmku80) has
allowed the introduction of a new gene in ringworm. This enabled analysis of
resistance to virulence factors and antifungal drugs (Yamada, Yamada, et al., 2014).
4 Other Issues for the Commercialization (Practical
Application Process)
Currently, stable gene disruption and gene insertion are possible for ringworm.
However, the method has not been commercialized because the following points
need to be resolved ((1)–(3)). Discovery and selection of target molecules by
promoting basic research for practical application are needed. Table 1 shows the
Table 1 Historical background from the basic research to the application stage
History of industry–academia collaboration
1994–2000 Joint research with Toyobo Gene Analysis
1995–2000 Adopted by the New Energy and Industrial Technology Development Organization
Commission (Proposal Open Call/Advanced Research and Development Project)
1998–2000 Japan Space Forum selected for public ground research on utilization of space
environment in 1998
2007–
Japan Aerospace Exploration Agency joint research on microbiota in the space station
2012–
Joint research with World Geno-matrix
2015–
Joint research with Airy Technology Co., Ltd.
Realities and Challenges of Bridging Research in Japan
143