In order to elucidate the molecular mechanism of endosymbiosis (secondary symbiosis) establishment, gene expressions obtained by transcriptome analyses in alga-free and algae-bearing Paramecium bursaria cells were compared. By mass-decoding cDNA using a next-generation DNA sequencer (HiSeq 2000 system by Illumina), attempts to identify the genes of P. bursaria involved in establishing endosymbiosis were made through comprehensive comparisons of mRNA. Timings of the gene expressions that are predicted to be involved in the re-establishment of endosymbiosis will be clarified by fluorescent in-situ hybridization (FISH) qualitative changes in the gene products, and their intracellular localizations, will be analyzed using monoclonal antibodies and the functions of the genes will be identified by RNAi.