Hormonal Determinants of Estrogen Receptor Binding and Response.

点击翻译按钮获取中文摘要

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.