Molecular analysis of genome stability/meiosis

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Ciliated protozoa such as Tetrahymena thermophila are characterized by having two nuclei in the same cell. The polyploid macronucleus (MAC) functions as the cell's somatic nucleus. The diploid micronucleus (MIC) is the cell's germinal nucleus. The MIC undergoes the special cell division called meiosis in this useful and much exploited animal model system. This proposal focuses on molecular studies of meiosis approached from the perspective of genome stability. Some of the areas of focus in this proposal are: 1) Meiosis in Tetrahymena is unusual in two important aspects; there is no synaptonemal complex (SC), a structure generally associated with the highly conserved process of meiosis; and, the elongated crescent structure of chromosomes in meiotic prophase I is very unusual. One can often learn more from studying differences in evolutionarily conserved processes rather than similarities so this system provides a powerful paradigm to address important questions about meiosis. 2) Genome stability is important for the life of an organism. Problems with genome stability can lead to problems including diseases. We will study genome stability through double strand break (DSB) repair. Relationships between DSB repair and DSBs in meiosis will be addressed. 3) DNA in a cell is organized as chromatin, i.e. it is associated with specific small, basic proteins called histones. Histone release and histone deposition is an important aspect of DNA replication. We will address questions about histone deposition focusing on DSB repair and on meiosis. 4) It has been thought that signaling by tyrosine phosphorylation was restricted to multicellular organisms. Recently, evidence has been presented that this pathway exists in unicellular eukaryotes. We have identified a novel tyrosine signaling pathway induced during cell pairing and early stages of mating in Tetrahymena. This study will have important implications for the evolution and function of tyrosine phosphorylation signaling in development. These studies using an exceptionally useful and versatile animal model organism provide important opportunities to train HQP studying important problems and using and developing state-of-the-art technologies.