DISSERTATION RESEARCH: Evolution of estrogen receptor function in mollusks

博士学位论文研究：软体动物雌激素受体功能的进化。俄勒冈州大学的Thornton June Keay几乎所有活细胞的功能都是由分子之间的特定相互作用来调节的，例如激素和受体之间的相互作用，酶和底物之间的相互作用，以及转录因子和DNA结合位点之间的相互作用。 然而，人们对这些分子相互作用是如何演变的知之甚少。 该项目的重点是雌激素-一组对脊椎动物发育和繁殖至关重要的激素-和雌激素受体（ER）蛋白之间相互作用的演变。在脊椎动物中，雌激素的结合使ER能够增加雌激素应答基因的表达。 初步数据表明，软体动物中的ER已经失去了与雌二醇的相互作用，并且无论激素是否存在，它总是激活转录。这种变异为研究ER与激素的功能相互作用的演变提供了机会。 具体来说，该项目将研究普通章鱼（Octopus vulgaris）ER功能的演变，章鱼是一种雌激素似乎具有生殖作用的软体动物。 章鱼ER的分子功能将被确定，ER序列的脊椎动物和软体动物的古老的共同祖先将被重建，和变体ER功能的进化的假设将通过合成的祖先受体和使用定点突变进行测试。 这项研究将为了解ER在人类和其他动物中的功能和进化提供重要的比较数据。它还将提供关于环境内分泌干扰的潜在范围的重要信息，这是环境和野生动物健康的一个主要问题。 该项目将通过支持在分子进化、基因功能和内分泌学的尖端技术方面对一名有才华的女科学家进行研究培训，为下一代科学家做出贡献。

DISSERTATION RESEARCH: EVOLUTION OF ESTROGEN RECEPTOR FUNCTION IN THE MOLLUSK, OCTOPUS VULGARISJoseph W. ThorntonJune KeayUniversity of Oregon Virtually all the functions of living cells are regulated by specific interactions between molecules, such as those between hormones and receptors, enzymes and substrates, and transcription factors and DNA binding sites. Very little is known, however, about how these molecular interactions evolved. This project focuses on the evolution of interactions between estrogens - a group of hormones crucial for development and reproduction in vertebrates -- and the estrogen receptor (ER) protein. In vertebrates, binding of estrogens enables the ER to increase expression of hormone-responsive genes. Preliminary data indicate the ER in mollusks has lost this interaction with estradiol, and that it always activates transcription, whether or not the hormone is present. This variation presents the opportunity to study the evolution of ER's functional interaction with hormones. Specifically, this project will investigate the evolution of ER function in the common octopus (Octopus vulgaris), a mollusk in which estrogen appears to have a reproductive role. The molecular functions of the octopus ER will be determined, the ER sequence of the ancient common ancestor of vertebrates and mollusks will be reconstructed, and hypotheses about the evolution of variant ER functions will be tested by synthesizing the ancestral receptor and using site-directed mutagenesis. This research will provide important comparative data for understanding ER function and evolution in humans and other animals. It will also provide important information on the potential scope of environmental endocrine disruption, a major issue in environmental and wildlife health. This project will contribute to the next generation of scientists by supporting the research training of a talented female scientist in cutting-edge techniques of molecular evolution, gene function, and endocrinology.