Investigating the role of phase separation in enhancer-dependent gene regulation

增强子是调控性的DNA序列，它控制在什么时候，在什么组织中，特定基因的开启和关闭。从增强子激活基因的过程需要许多因素，包括结合基因组中增强子区域的表观遗传酶，以及从增强子转录的非编码rna （eRNAs）。相分离最近成为生物学中最令人兴奋和发展最快的领域之一。相分离凝聚物是含有高密度蛋白质和核酸的无膜细胞器。它们与周围的细胞环境相分离，提供了一种在细胞核中划分和集中生化反应的方法。最近的证据指出，相分离凝析油作为高活性增强剂的调节剂的作用。在这个项目中，我们将开发新的方法来了解相分离如何影响负责增强子功能的酶的活性。您将加入谢菲尔德核酸研究所内一个高度协作和动态的研究环境，在那里您将学习尖端的方法，包括下一代测序，RNA生物学，实时成像（单分子FRET）和生化方法来研究染色质修饰。这项工作将为生物学中最相关的问题之一提供新的认识，并将产生广泛的成果，从了解人类疾病到改善生物技术。

Enhancers are regulatory DNA sequences that control when, and in what tissue,particular genes are turned on and off. The process of gene activation fromenhancers requires a number of factors, including epigenetic enzymes that bindto enhancer regions in the genome, and non-coding RNAs (eRNAs) transcribedfrom enhancers.Phase separation has recently emerged as one of the most exciting and fast-moving areas of biology. Phase separated condensates are membranelessorganelles containing high densities of proteins and nucleic acids. They exist ina separate phase to the surrounding cellular environment, providing a method tocompartmentalize and concentrate biochemical reactions in the nucleus.Recent evidence has pointed to a role for phase separated condensates asregulators of highly active enhancers. In this project, we will develop newmethodologies to understand how phase separation affects the activity ofenzymes responsible for enhancer function. You will join a highly collaborativeand dynamic research environment within the Sheffield Institute for NucleicAcids, where you will learn cutting edge approaches including next generationsequencing, RNA biology, real time imaging (single molecule FRET) andbiochemical approaches to study chromatin modifications. The work will providea new understanding of one of the most relevant questions in biology and willhave broad ranging outcomes, from understanding human diseases to improvingbiotechnology.