Grant: Operating Grant

The unicellular eukaryotic microorganisms, the ciliated protozoa, are recognized as exceptionally useful and important animal models for addressing basic biological questions with relevance for practical applications including human health. One well studied member of this group, Tetrahymena thermophila has typical eukaryotic biology. Its ultrastructure, cell physiology, development, biochemistry, genetics, and molecular biology have been extensively investigated. This organism displays a degree of cellular, structural, and functional complexity comparable to that of human and other metazoan cells. At the molecular level, Tetrahymena's rich and complex genome conserves a rich set of ancestral eukaryotic functions. In addition, Tetrahymena's special elaborations of certain basic eukaryotic mechanisms have facilitated discoveries opening the door to major new fields of fundamental research such as telomeres and telomerase, catalytic RNA and ribozymes, histone modification and epigenetic developmental mechanisms, and much more. The richness of Tetrahymena's biology makes it a genetic unicellular animal model organism "for all seasons." An impressive array of novel molecular genetic technologies places Tetrahymena at the forefront of experimental, in vivo functional genomics research, and complements a wealth of favorable biological features. The recent complete sequencing of the 104 MB somatic genome with the identification of many orthologs of human disease genes provides additional experimental opportunity for addressing basic biological questions of significance and with implications for human health. Our research will focus on molecular and biochemical studies of developmentally programmed gene reorganization and genome surveillance and silencing via an RNAi-dependent heterochromatin mechanism, as well as on gene expression and proteomics to identify and analyze interesting and important proteins including orthologs of human disease genes.