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

增强子是一种调控DNA序列，它控制特定基因在什么时候以及在什么组织中被打开和关闭。由增强子激活基因的过程需要一系列因素，包括与基因组中增强子区域结合的表观遗传酶，以及由增强子转录的非编码RNA(ERNAs)。相分离冷凝物是一种无膜细胞器，含有高密度的蛋白质和核酸。它们以独立的相存在于周围的细胞环境中，提供了一种方法来分隔和集中细胞核中的生化反应。最近的证据表明，相分离的冷凝物作为高活性促进剂的调节器。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高度协作和动态的研究环境，在那里您将学习尖端方法，包括下一代测序、RNA生物学、实时成像(单分子FRET)和研究染色质修饰的生化方法。这项工作将为生物学中最相关的问题之一提供新的理解，并将产生广泛的结果，从理解人类疾病到改进生物技术。

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.