TORC1是调节细胞生长和代谢的关键通路。GATOR复合体通过动态控制TORC1活性，调节果蝇卵细胞的生长与分化，但对其如何在分子水平调节减数分裂进程仍不清楚。DNA双链断裂（DSB）是同源染色体重组的基础，但过多的DSB会引起基因组的不稳定。本项目以GATOR1复合体的组分蛋白Nprl2、Nprl3、Iml1的基因突变和转基因果蝇为对象，通过研究GATOR1突变体卵细胞中的DSB水平、p53活性、同源重组效率、转座子活化等，阐明GATOR1复合体的分子功能；通过研究减数分裂DSB的生成与修复、TORC1活性、p53通路等对GATOR1突变体卵细胞中DSB水平、p53活性及细胞凋亡的影响，阐明GATOR1复合体保护早期卵细胞的机制。本项目将揭示GATOR1复合体在昆虫卵细胞基因组稳定中的作用，为干预昆虫生殖提供新思路，也为研究高等动物减数分裂机制提供理论支持。

Target of Rapamycin Complex 1 (TORC1) is a master regulator that mediates nutrient status and cell growth. Previously, we found that the GATOR1 complex, comprised of the Nprl2, Nprl3 and Iml1 proteins, is an inhibitor of TORC1 and plays important roles in meiotic entry and cell survival under starvation. However, the molecular mechanism of GATOR1 on meiotic cell cycle is little known. Meiosis promotes genomic diversity through homologous recombination, a process require DNA double-stranded breaks (DSBs). On the other hand, DSBs represent a dangerous form of DNA damage that can result in dramatic and permanent changes to the genome. Thus, the DSB formation must be exquisitely controlled during gamete formation. Here our preliminary data show that GATOR1 mutant oocytes accumulate an increased number of DSBs and activity of p53 in early prophase of meiosis I. These results suggest that the GATOR1 is required for maintaining genomic stability. This project will study the DSB, p53 activity, homologous chromosomes recombination rate and transposable element (TE) expression in Drosophila oocyte to elucidate the molecular function of GATOR1 complex. Through inhibiting meiotic DSB machines, TORC1 activity and p53 pathway, the mechanism of GATOR1 regulating DSB formation, p53 activity and cell death during early meiosis will be determined. This project will elucidate the link between the metabolic pathway and genomic stability in germ line. This work will provide new idea for insect reproduction control and theoretical support for mammal meiosis mechanism.