- Using the roundworm C. elegans for drug screening
Using the roundworm C. elegans for drug screening
Outline of Seeds
The C. elegans roundworm is a model organism suitable for mass-screening of genetic mutations and reagents. The shape of the C. elegans male tail is controlled by a variety of factorssemaphorin being one example. Semaphorin is a protein known as a major guidance factor for growing axons in vertebrates, and is present in roundworms as well. The arrangement of sensory organs in the tail known as ray 1 and ray 2 becomes abnormal in the semaphorin mutants (see figure 1). We are using this trait as a clue to elucidate semaphorin signaling pathways. By using genetic and biochemical techniques, we have revealed that the semaphorins modulate the mTOR signaling, thereby down-regulating the PKC activity by reducing TORC2 while stimulating mRNA translation by increasing TORC1 (see figure 2).
Novelty and originality of this research
Exploiting the morphology of the tail of C. elegans roundworms as a readout of the semphorin signal has been uniquely established by our team. The aforementioned findings it has yielded are also original, which have been published in international journals with positive reception. In general, the signal pathways that exist in roundworms are known to correspond directly to those in all vertebrates, including humans. Compared to mice and zebrafish, roundworms are cheap and can be bred and maintained in large numbers, providing a highly superior experimental system in terms of studying signal pathways at the organism level under physiological conditions. This system would be particularly suitable for screening drugs modulating the semaphorin and the mTOR signaling.
Drug screen by using a handy experimental system with roundworms has a particular advantage, in particular in the primary screen
- Culture chambers, Nomarski microscope, fluorescence microscope, IR-LEGO, Nipkow disk confocal microscope, etc.
Monographs, Papers and Articles
- Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2alpha in C. elegans. Akira Nukazuka, Hajime Fujisawa, Toshifumi Inada, Yoichi Oda, & Shin Takagi. Genes & Development. 22, 1025-1036 (2008)
- A shift of the TOR adaptor from Rictor towards Raptor by Semaphorin in C. elegans. Akira Nukazuka, Shusaku Tamaki, Kunihiro Matsumoto, Yoichi Oda, Hajime Fujisawa & Shin Takagi. Nature Communications 2 484 DOI:10.1038/ncomms1495, (2011)