Regulation of Protein Synthesis and Degradation During Invertebrate Quiescence

9306652手这项工作将研究某些细胞和组织如何能够在休眠状态下长时间存活，在休眠状态下，能量代谢和发育被关闭。对虾胚胎(Artemia Franciscana)是概述的实验的重点，因为它们在休眠中存活数月甚至数年的非凡能力是众所周知的。对于任何休眠状态，如果一个生物体要忍受一轮又一轮的休眠，有两个问题必须解决。首先，必须协调一致地抑制能源使用和能源生产。其次，大分子的完整性必须在这段时间内保持不变，因为几乎没有能量可以用来替换或修复它们。之前对这些胚胎的研究表明，一个细胞信号可能参与了这两种现象的调节。这项工作的第一个目标是解释像蛋白质合成这样的能量消耗过程是如何真正关闭的。我们将比较限制指导细胞合成蛋白质的信息拷贝(即信使RNA)与实际抑制构建蛋白质的机器本身(核糖体)的相对效果。最后，由于合成在休眠期间以某种方式受到抑制，因此也必须阻止蛋白质降解的速度，以避免大分子的耗尽。因此，第二个目标是了解蛋白质的降解(活跃细胞中的正常过程)是如何减少的。解释蛋白质在休眠期间是如何保存的(实际上，处于休眠状态)应该会提供一些见解，这些见解将对其他生物系统有用，在这些系统中，生存依赖于从物理和化学侮辱中成功恢复。对于许多新陈代谢不可避免地受到抑制或干扰的情况，细胞能够承受长时间静止的机制往往具有重要的意义--器官组织移植、组织血流的急性阻塞和缺氧。***

9306652 Hand This work will investigate how certain cells and tissues are able to survive long periods of time in dormant state, where energy metabolism and development are shutdown. Shrimp embryos (Artemia franciscana)are the focus of the outlined experiments, because their remarkable capacity to survive dormancy for months and even years is well known. For any dormant state, there are two problems that must be solved if an organisms is to tolerate bouts of quiescence. First, there must be a coordinated suppression of both energy use and energy production. Second, the integrity of macromolecules must be preserved during this period when little energy is available for their replacement or repair. Previous work with these embryos suggests that one cellular signal may be involved in mediating both of these phenomena. The first goal of the work is to explain how an energy consuming process like the synthesis of protein is indeed shutdown. The relative effect of limiting the copies of message (i.e., messenger RNA) that direct the cell to synthesize proteins, versus actually inhibiting the machinery itself (ribosomes) that builds the proteins will be compared. Finally, since synthesis is in some way suppressed during dormancy, then the rate of protein degradation must also be arrested in order to avoid depletion of macromolecules. Therefore, the second aim is to understand how degradation of protein (a normal process in an active cell)is reduced. Explaining how proteins are preserved during dormancy (in effect, placed into suspended animation) should provide insights that will be useful for other biological systems where survival depends on successful recovery from physical and chemical insults. The mechanisms by which cells can withstand long bouts of quiescence are apt to have important implications for numerous cases where metabolism is unavoidably suppressed or disrupted-- organ tissue transplantation, acute blockage of blood flow to tissues, and oxygen deprivation. ***