Arrest of Gene Expression During Invertebrate Quiescence

手97-23746的休眠为动物提供了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由除氧(缺氧)引起的长时间休眠中存活下来。在缺氧的情况下，能量代谢和发育都会停止。本项目有三个具体的研究目标。首先，将测量从活跃动物和休眠动物分离的细胞核和线粒体的转录速度(从DNA合成信使RNA)。PI的预测是，转录将在缺氧下被抑制，这与我们的实验动物(虾胚胎)在缺氧下停止发育的事实是一致的。其次，对信使RNA(信使RNA)在缺氧条件下的稳定性进行了测定。PI的假设是，在休眠期间，mRNA的降解(活跃细胞中的一个正常过程)将被抑制。在休眠状态下保持信使核糖核酸分子的保守，可能有利于蛋白质合成在氧气恢复后迅速恢复。第三，PI将假设在这些动物的线粒体中有一个氧传感器，当氧气可获得性降低时，它可以控制蛋白质合成的速度。将进行实验以测试传感器是否是家庭蛋白(即，类似于血红蛋白等氧结合蛋白)。细胞经受长时间休眠的机制往往对许多新陈代谢不可避免地被扰乱的病例具有重要意义--器官和组织移植、组织血流的急性阻断和缺氧。从生态学的角度来看，这项工作应该有助于解释促进进入休眠的环境刺激是如何与必要的生存反应联系在一起的。、。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