Dissecting the evolution of 3D genome structure with Pore-C nanopore sequencing

目的：本项目的目的是以线虫为代表，利用ONT Pole-C方法，研究高阶基因组结构的进化及其与低水平基因组特征(重复含量、杂合性和DNA甲基化)的相关性。目的：为了解决这个问题，我们将实现三个主要的实验和计算目标：-目标1：在成虫中重建高阶基因组结构。-目标2：在成虫中描述与染色质构象相关的全基因组DNA甲基化模式(5mC)，并从功能上探索DNA甲基化对染色质结构的影响。-目标3：开发新的软件解决方案，在高杂合度和高重复含量的情况下，从孔洞-纳米孔数据重建高序基因组结构，同时称为甲基化。符合BBSRC的职责范围：这一学术界和产业界的合作符合并解决了BBSRC的核心研究优先事项：“系统生物学”(通过计算生物学了解高阶DNA结构)、“数据驱动生物学”和“生物科学的技术开发”(为“组学”技术生成新的软件应用，特别是在混乱的基因组环境下解决染色体规模的DNA结构)。项目影响：该项目将(I)提供对3D基因组结构原理的基本理解；(Ii)开发新的软件解决方案来研究基因组结构；以及(Iii)促进学术界和产业界的合作，以加强英国生物科学在“组学”领域的领先地位。博士生将每周与学术和非学术主要导师举行一对一会议，以监测进展情况。博士生将参加每周一次的实验室会议，有机会与主要学术和非学术实验室的其他成员分享数据并获得反馈，学生还将定期(两周或每月)与二级学术导师接触。这位博士生将积极参加QMUL表观基因组学中心的会议，该中心由13名研究人员组成，他们因对基因组调控的共同兴趣而团结在一起，并参加SBCS系研讨会系列会议，在那里，博士生和博士后每年一次向更广泛的受众介绍他们的项目，并从不同的专业人士那里获得反馈。此外，学生和主要的学术和非学术导师将通过团队合作应用程序进行现场或远程日常交流。

Aim: The aim of this project is to investigate how high-order genome structure evolves and corelates withlow-level genomic features (repeat content, heterozygosity and DNA methylation) using as proxy annelidworms and exploiting ONT Pore-C methodology.Objectives: To address this aim, we will implement three main experimental and computational objectives:- Objective 1: Reconstruct high-order genome structure in adults of the annelids Owenia fusiformis andCapitella teleta.- Objective 2: Profile genome-wide DNA methylation patterns (5mC) in adult O. fusiformis and C. teleta inrelation to chromatin comformation and functionally explore the impact of DNA methylation in chromatinstructure.- Objective 3: Develop new software solutions to reconstruct high-order genome structure from Pore-Cnanopore data in cases of high heterozygosity and high repeat content, simultaneously calling methylation.Fit into BBSRC remit: This academy-industry collaboration aligns with and addresses core BBSRC researchpriorities: "Systems Biology" (understanding high-order DNA structure through computational biology), "DataDriven Biology" and "Technology Development for the Biosciences" (generation of new software applicationsfor 'omics' technologies, in particular to resolve chromosome-scale DNA structure under confoundinggenomic contexts).Project impact: This project will (i) provide fundamental understanding of the principles of 3D genomestructure; (ii) generate novel software solutions to the study of genome structure; and (iii) foster academyindustrycollaborations that strengthen the leading position of UK biosciences in the 'omics' field.The PhD student will have weekly one-to-one meetings with the academic and non-academic mainsupervisors to monitor progress. The PhD student will participate in weekly lab meetings where there will bethe opportunity to share data and get feedback with other members of the main academic and non-academiclab, and the student will also engage with the secondary academic supervisors on a regular basis (fortnightlyor monthly). The PhD student will actively participate in the meetings of the QMUL Epigenomics Hub, a groupof 13 researchers united by their common interest on genomic regulation, and in the SBCS departmentalseminar series, where once per year PhD students and postdocs present their projects to a wider audienceand gain feedback from different expertises. In addition, the student and main academic and non-academicsupervisors will communicate on a daily basis either on-site or remotely via team-working apps.