A novel method to study the three dimensional organisation of the genome during DNA replication

Project Overview

Double strand breaks in DNA are the initiating lesion for the translocation events that underlie the genome instability that causes cancer. However, the three dimensional organisation of the genetic material within the nucleus also influences the outcome of translocations because proximity of DNA strands increases the risk of their inappropriate joining. DNA replication has a dramatic effect both on break formation and on 3D nuclear organisation, but its roles in oncogenic translocations are undefined.

My group has a longstanding interest in DNA replication and its regulation. We have recently developed new techniques (Repli3C, Repli4C and Repli-C) to analyse the changes in genome organisation that accompany DNA replication. These methodologies are similar to the existing techniques of chromosome conformation capture (3C, 4C, Hi-C) but with the addition of EdU incorporation and affinity purification to enrich for newly replicated regions. In this project we will optimise and refine these techniques and then use them to investigate the influence of DNA replication on the formation of the translocations that drive the development of cancer.

The intended aims are:

The project will suit a student interested in a combination of wet-lab research and bioinformatic analysis of genome wide datasets. Completion of this study will bring new insight into the formation of the genomic rearrangements that can underlie the development of a significant proportion of cancers.

Training Opportunities

The research will take place in our state of the art laboratories in the Wellcome Trust Centre for Human Genetics at the University of Oxford. There will be the opportunity to learn or develop skills in cell and molecular biology, protein biochemistry, advanced microscopy techniques and bioinformatics, with support from core facilities and collaborative opportunities across the Department.

Theme

Cancer Biology and Genetics & Genomics

Admissions

Project reference number: 765

Funding and admissions information

Supervisors

Name Department Institution Country Email
Professor Catherine Green Wellcome Trust Centre for Human Genetics Oxford University, Henry Wellcome Building of Genomic Medicine GBR catherine.green@well.ox.ac.uk
Professor Ian Tomlinson Wellcome Trust Centre for Human Genetics Oxford University, Henry Wellcome Building of Genomic Medicine GBR iant@well.ox.ac.uk

There are no publications listed for this DPhil project.