Molecular analysis of genome stability/meiosis

有纤毛的原生动物如嗜热四膜虫的特征是在同一个细胞中有两个细胞核。多倍体大核（MAC）作为细胞的体细胞核。二倍体微核（MIC）是细胞的生殖核。在这个有用的和被广泛利用的动物模型系统中，MIC经历了称为减数分裂的特殊细胞分裂。该建议侧重于从基因组稳定性的角度对减数分裂进行分子研究。在这个建议中的一些重点领域是：1）四膜虫减数分裂在两个重要方面是不寻常的;没有联会复合体（SC），通常与高度保守的减数分裂过程相关的结构;和，在减数分裂前期I染色体的细长新月结构是非常不寻常的。人们通常可以从研究进化保守过程中的差异而不是相似性中学到更多，因此该系统提供了一个强大的范式来解决减数分裂的重要问题。2)基因组的稳定性对生物体的生命至关重要。基因组稳定性的问题可能导致包括疾病在内的问题。我们将通过双链断裂（DSB）修复研究基因组稳定性。DSB修复和DSB之间的关系在减数分裂将被解决。3)细胞中的DNA组织为染色质，即它与称为组蛋白的特定小碱性蛋白质相关。组蛋白的释放和沉积是DNA复制的一个重要方面。我们将讨论有关组蛋白沉积的问题，重点是DSB修复和减数分裂。4)人们一直认为，酪氨酸磷酸化信号仅限于多细胞生物。最近，有证据表明，这一途径存在于单细胞真核生物。我们已经确定了一种新的酪氨酸信号通路诱导细胞配对和交配的早期阶段在四膜虫。 这项研究将对发育中酪氨酸磷酸化信号的演变和功能产生重要影响。这些研究使用了非常有用和通用的动物模型生物体，为培训HQP研究重要问题以及使用和开发最先进的技术提供了重要的机会。

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.