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

Aim: The aim of this project is to investigate how high-order genome structure evolves and corelates with
low-level genomic features (repeat content, heterozygosity and DNA methylation) using as proxy annelid
worms 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 and
Capitella teleta.
- Objective 2: Profile genome-wide DNA methylation patterns (5mC) in adult O. fusiformis and C. teleta in
relation to chromatin comformation and functionally explore the impact of DNA methylation in chromatin
structure.
- Objective 3: Develop new software solutions to reconstruct high-order genome structure from Pore-C
nanopore 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 research
priorities: "Systems Biology" (understanding high-order DNA structure through computational biology), "Data
Driven Biology" and "Technology Development for the Biosciences" (generation of new software applications
for 'omics' technologies, in particular to resolve chromosome-scale DNA structure under confounding
genomic contexts).
Project impact: This project will (i) provide fundamental understanding of the principles of 3D genome
structure; (ii) generate novel software solutions to the study of genome structure; and (iii) foster academyindustry
collaborations 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 main
supervisors to monitor progress. The PhD student will participate in weekly lab meetings where there will be
the opportunity to share data and get feedback with other members of the main academic and non-academic
lab, and the student will also engage with the secondary academic supervisors on a regular basis (fortnightly
or monthly). The PhD student will actively participate in the meetings of the QMUL Epigenomics Hub, a group
of 13 researchers united by their common interest on genomic regulation, and in the SBCS departmental
seminar series, where once per year PhD students and postdocs present their projects to a wider audience
and gain feedback from different expertises. In addition, the student and main academic and non-academic
supervisors will communicate on a daily basis either on-site or remotely via team-working apps.