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Dissecting the evolution of 3D genome structure with Pore-C nanopore sequencing
Closing date
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Supervisors
Dr Chema Martín-Durán , chema.martin@qmul.ac.uk, Senior Lecturer in Organismal Biology, Queen Mary University of London
Project Details

Background

The 3D structure of the genome – the set of DNA molecules with the guidelines to build an organism – is fundamental for proper expression of the genetic information contained in it [1]. However, how this 3D structure evolves and is influenced by other features of the genome is still unclear. This is because our understanding of this biological phenomenon is mostly limited to a handful of model organisms and by the fact that current methods to reconstruct the 3D structure of genomes depend on short-read sequencing. In late 2019, Oxford Nanopore Technologies (ONT) released Pore-C, a method to apply long-read sequencing to reconstruct 3D genome structure that overcomes current limitations in chromatin conformation approaches [2]. In parallel, the Martín-Durán lab is establishing a set of  marine segmented worms (annelids) as research model systems for comparative evolutionary genomics [3]. What are the genomic features controlling 3D genome structure in annelids? How do these mechanisms generate variability in 3D genome structure among species? Can we develop Pore-C as a widespread approach to reconstruct 3D genome structure?

  • In this project, you will rigorously answer these questions combining state-of-the-art experimental and computation approaches in a unique academic-industry collaborative environment.
  • You will have access to large genomic databases, and in-house live organisms to fuel your investigation.
  • You will gain experience of molecular techniques (epigenomics, nanopore long-read sequencing), bioinformatics (pipelines to analyse Pore-C data), and statistics.
  • You will be encouraged to develop your own ideas and hypotheses.

This is a BBSRC LIDo iCASE PhD funded position. The student will become part of Queen Mary’s Doctoral College, which provides training and development opportunities and financial support for research. The student will also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career. In addition, the student will enjoy a 6-months placement at Oxford Nanopore Technologies headquarters in Oxford (UK), where the students will integrate within the research and development team.

Skills preferred

In a multidisciplinary project like this, candidates are unlikely to have a background in all disciplines involved.  The most important qualification is motivation, enthusiasm and that the project appeals to you. However, previous computational experience would be important. We can envisage strong candidates coming through a variety of routes including:

- practical molecular biology

- developmental and cell biology

- biotechnology

- computational biology

To apply, students should have a 1st class degree or have received a MSc in a relevant field (i.e. molecular biology, genetics and evolutionary genomics, developmental and cell biology, biotechnology, bioinformatics) or are about to finish their MSc.

References

[1] Rowley, M.J., Corces, V.G. (2018) Organizational principles of 3D genome architecture. Nat Rev Genet 19, 789–800. https://doi.org/10.1038/s41576-018-0060-8

[2] Netha Ulahannan, Matthew Pendleton, Aditya Deshpande, Stefan Schwenk, Julie M. Behr, Xiaoguang Dai, Carly Tyer, Priyesh Rughani, Sarah Kudman, Emily Adney, Huasong Tian, David Wilkes, Juan Miguel Mosquera, David Stoddart, Daniel J. Turner, Sissel Juul, Eoghan Harrington, Marcin Imielinski (2019) Nanopore sequencing of DNA concatemers reveals higher-order features of chromatin structure. bioRxiv 833590; doi: https://doi.org/10.1101/833590

[3] José M. Martín-Durán, Bruno C. Vellutini, Ferdinand Marlétaz, Viviana Cetrangolo, Nevena Cvetesic, Daniel Thiel, Simon Henriet, Xavier Grau-Bové, Allan M. Carrillo-Baltodano, Wenjia Gu, Alexandra Kerbl, Yamile Marquez, Nicolas Bekkouche, Daniel Chourrout, Jose Luis Gómez-Skarmeta, Manuel Irimia, Boris Lenhard, Katrine Worsaae, Andreas Hejnol (2020) Conservative route to genome compaction in a miniature annelid. bioRxiv 2020.05.07.078311; doi: https://doi.org/10.1101/2020.05.07.078311

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