Hormonal Determinants of Estrogen Receptor Binding and Response.

雌激素受体(ER)在乳房发育中起着核心作用，当它出了问题时，也会在疾病中发挥核心作用。组织发育中的一个关键问题是，是什么导致不同的细胞对分子信息表现出协调的反应，以及这种调节是如何维持的。雌激素是脂溶的，可以跨细胞膜扩散。因此，内质网是一个核受体。在激活时，ER在数千个位置直接与基因组DNA结合，并打开附近的基因。这项研究旨在阐明其他激素在定义潜在染色质景观中的作用，染色质景观限制ER与DNA结合的位置，从而定义哪些基因对雌激素有反应。为了实现我们的目标，我们将结合单细胞RNA测序和修改后的ER。我们修改后的内质网将在附近的DNA上留下标记，使用户能够监测其他激素如何定义内质网结合的位置。而单细胞测序使我们能够监测对雌激素的反应以及它在单个细胞之间的变化。理想的候选人应该具有分子、细胞或发育生物学方面的背景。

The Estrogen Receptor (ER) plays a central role in breast development, and when it goes wrong, in disease. A key question in tissue development is whatcauses different cells to show a coordinated response to the molecular messages and how is this regulation maintained.Estrogen is lipid-soluble and diffuses across cell membranes. As a result, the ER is a nuclear receptor. On activation, the ER directly binds to genomicDNA at thousands of locations and turns-on nearby genes. This research aims to elucidate the role of other hormones in defining theunderlying chromatin landscape, which restricts where ER can bind to DNA, thereby defining which genes respond to estrogen.To achieve our goal, we will combine single-cell RNA sequencing with a modified ER. Our modified ER will leave markers on nearby DNA enabling usto monitor how other hormones define where ER can bind. While single-cell sequencing enables us to monitor the response to estrogen and how itvaries between individual cells. The ideal candidate should have a background in molecular, cell or developmental biology.