Neuropeptide Control of Ecdysone Biosynthesis

昆虫和其他节肢动物要想生长，就必须蜕皮。也就是说，它们必须脱去限制生长的外层覆盖物(外骨骼)，同时合成一个新的更大的版本。这种蜕皮的能力使昆虫得以存活并繁衍了数亿年。实际的蜕皮过程是由一种类固醇激素20-羟基蜕皮酮(20E)诱导和控制的，这种激素是由特殊的腺体合成的。哺乳动物也使用类固醇激素来控制新陈代谢活动和第二性征。尽管20E的化学特征大约在50年前就被确定了，但直到几年前，这个实验室使用分子遗传学技术来鉴定、克隆和鉴定参与20E生物合成最后四步的酶编码基因时，人们对它的合成方式知之甚少。然而，在这个方案中，有几个先前的步骤不存在信息，即所谓的黑匣子，这项提议的目标是识别控制这些步骤的基因。为这项工作开发的实验范式涉及分子遗传学和生物化学的结合，是新颖的，可以用于包括人类在内的哺乳动物类固醇激素生物合成的研究。此外，解开20E的生物合成方案可能会确定这种昆虫特有的生化步骤，并可以用新的抑制剂来探索，以控制具有生物医学和农业重要性的害虫。该实验室将一如既往地对本科生进行上述技术培训。目前，两名女学生，一名少数民族血统的学生将参与这个项目。

For insects and other arthropods to grow they must molt. That is, they must shed their outer covering (exoskeleton) which restricts growth, while synthesizing a new and larger version. This ability to molt has allowed insects to survive and prosper for hundreds of millions of years. The actual molting process is elicited and controlled by a steroid hormone, 20-hydroxyecdysone (20E), which is synthesized by special glands. Mammals also use steroid hormones to control metabolic activities and secondary sexual characteristics. Although 20E was characterized chemically about 50 years ago, little was known about how it is synthesized until a few years ago when this laboratory used molecular genetic techniques to identify, clone and characterize genes encoding enzymes mediating the last four steps in the biosynthesis of 20E. However, there are several prior steps in this scheme for which no information exists, the so-called black box, and the goal of this proposal is to identify the genes controlling these steps. The experimental paradigms developed for this work involving the marriage of molecular genetics and biochemistry are novel and can be utilized for the study of steroid hormone biosynthesis in mammals including man. Further, unraveling the biosynthetic scheme for 20E may identify biochemical steps unique to the insect and could be probed with new inhibitors to control pests of biomedical and agricultural importance. This laboratory will continue to train undergraduates in the aforementioned technologies as it has in the past. Currently, two female students, one of minority heritage are slated to work on this project.