Arrest of Gene Expression During Invertebrate Quiescence

手97-23746 休眠是动物在恶劣环境条件下生存的重要手段。这项工作将研究某些细胞如何能够在长时间的休眠中存活下来，这种休眠是由氧气的去除（缺氧）引起的。在缺氧状态下，能量代谢和发育被关闭。 该项目有三个具体的研究目标。首先，将在从活跃动物和休眠动物分离的细胞核和线粒体中测量转录速率（从DNA合成信使RNA）。 PI的预测是，在缺氧条件下转录将被抑制，这与我们的实验动物（虾胚胎）在缺氧条件下发育停止的事实一致。第二，测定缺氧条件下信使RNA（mRNA）的稳定性。PI的假设是，mRNA的降解（活跃细胞中的正常过程）将在休眠期间受到抑制。休眠期间mRNA分子的保存可能有利于氧气一旦恢复就迅速恢复蛋白质合成。第三，PI将假设这些动物的线粒体中存在氧传感器，当氧气可用性降低时，该氧传感器可以控制蛋白质合成的速率。将进行实验以测试传感器是否是家庭蛋白质（即，类似于氧结合蛋白，如血红蛋白）。 细胞能够经受住长时间休眠的机制，对于许多新陈代谢被严重破坏的情况--器官和组织移植、流向组织的血液急性阻塞以及缺氧--往往具有重要意义。从生态学的角度来看，这项工作应该有助于解释如何促进进入休眠的环境刺激与所需的生存反应。 ,,. 1

Hand 97-23746 Dormancy in animals provides an important means to survive harsh environmental conditions. This work will investigate how certain cells are able to survive long periods of dormancy that are induced by the removal of oxygen (anoxia). Under anoxia, energy metabolism and development are shut down. There are three specific research objectives for this project. First, the rate of transcription (synthesis of messenger RNA from DNA) will be measured in nuclei and mitochondria isolated from active animals and dormant animals. The PI's prediction is that transcription will be depressed under anoxia, which would be consistent with the fact that development ceases under anoxia in our experimental animal (a shrimp embryo). Second, the stability of messenger RNA (mRNA) under anoxia will measured. The PI's hypothesis is that degradation of mRNA (a normal process in active cells) will be is depressed during dormancy. Conservation of mRNA molecules during dormancy might favor a quick resumption of protein synthesis as soon as oxygen is returned. Third, the PI will hypothesize that there is an oxygen sensor in the mitochondria of these animals that can control the rate of protein synthesis when oxygen availability is reduced. Experiments will be performed to test whether or not the sensor is a home protein (i.e., similar to oxygen binding proteins like hemoglobin). The mechanisms by which cells withstand long bouts of dormancy are apt to have important implications for numerous cases where metabolism is unavoidably disrupted -organ and tissue transplantation, acute blockage of blood flow to tissues, and oxygen deprivation. From an ecological perspective, the work should help explain how environmental stimuli that promote entry into dormancy are linked to the required survival responses. ,,. 1