Bisulfite-free and base-resolution single-cell DNA epigenetic sequencing

Project Overview

Bisulfite-free, base-resolution, and quantitative sequencing of cytosine modifications with TAPS ...

Combine TAPS with enrichment for single-cell DNA epigenetic sequencing

Background

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the two major epigenetic modifications found in the mammalian genome and they played important roles in a broad range of biological processes from gene regulation to initiation and progression of many human diseases. It is also becoming clear that human tissue is highly heterogeneous in terms of the genome, transcriptome, and epigenome. Defining cell identity and lineages based on epigenetic profiling may provide insights into identity crucial events in normal and disease development. Despite both a strong need and a compelling hypothesis for studying the epigenetic heterogeneity, single-cell epigenetics is far less utilized than single-cell transcriptomics because the current methods (bisulfite sequencing) for detecting epigenetics are not feasible for small or rare cellular subpopulations.

Aims and Objectives

We combine various chemical biology and genome technologies to develop novel tools in epigenetics. Recently we developed novel bisulfite-free and base-resolution sequencing technologies for DNA methylation and hydroxymethylation (bioRxiv doi: https://doi.org/10.1101/307538, Figure 1). It could replace bisulfite sequencing as the new standard in DNA epigenetic analysis. We expect it to revolutionize DNA epigenetic analysis, and to have wide applications in academic research and clinical diagnostics, especially in sensitive low-input samples, such as circulating cell-free DNA and single-cell analysis. This project aims to apply this method to develop comprehensive and scalable single-cell DNA methylation and hydroxymethylation sequencing (Figure 2). It will be applied to various systems through collaborations, such as embryonic development, hematopoietic stem cell, and tumour development.

Training Opportunities

Training opportunities include a wide range of basic and advanced molecular biology/biochemistry/chemical biology techniques, as well as next-generation sequencing techniques and bioinformatics data-analysis. Training will be provided in all of these areas.

Theme

Genetics & Genomics

Admissions

Project reference number: 985

Funding and admissions information

Supervisors

Name Department Institution Country Email
Dr Chunxiao Song Oxford Ludwig Institute Oxford University, NDM Research Building GBR chunxiao.song@ludwig.ox.ac.uk
Professor Skirmantas Kriaucionis Oxford Ludwig Institute Oxford University, Old Road Campus Research Building GBR skirmantas.kriaucionis@ludwig.ox.ac.uk

There are no publications listed for this DPhil project.