Structural biology of genome folding

Qualification: PhD

Department: Molecular and Cell Biology

Application deadline: 4th May 2021

Start date: 27th September 2021

Overview

Supervisors: 

Professor Daniel Panne   E: daniel.panne@leicester.ac.uk

Dr Thomas Schalch   E: thomas.schalch@leicester.ac.uk

Project description:

It has been proposed that DNA folding by a process called ‘loop extrusion’ is a central organising principle of genome conformation. The hypothesis is that loop extrusion reels in genomic DNA into loops, a process which ‘individualises’ chromatin fibres and brings distant loci into proximity. The resulting higher-order packing of chromosomal DNA is thought to have important structural and regulatory consequences for a number of DNA-based processes.

We discovered recently that a subunit of the cohesin complex interacts directly with the chromatin insulator CTCF and that this interaction is required for the formation of loops at TAD boundaries. Similar CTCF-like motifs are present in a number of additional genome regulators that each control different key chromosomal process. Our hypothesis is that these interactions specify where in the genome cohesin productively catalyses DNA looping.

The exciting possibility arises that loop extrusion by cohesin thus contributes to a number of fundamental genome transactions including DNA replication, repair and transcription. We here propose an interdisciplinary approach involving biochemical and structural biology approaches to study how cohesin and CTCF interact with chromatin. We will specifically seek a bottom-up understanding of how these interactions control 3D genome organisation and contribute to fundamental aspects of genome biology.

The project involves detailed biochemical studies, recombinant overexpression of individual components and subcomplexes together with structural studies by cryoEM. This will form part of a larger interdisciplinary project with integrative imaging across scales, including super-resolution STORM and higher-resolution CLEM imaging to study large-scale chromosomal features. We will also use genomics approaches such as Hi-C to assess the consequences for genome folding, and will study how these interactions direct cohesin’s localization and residence time on chromatin.

References: 

Nature 578, 472–476 (2020); NSMB 27, 233–239 (2020); Nature 562, 538–544 (2018).

 

Funding

Funding

College of Life Sciences Studentship providing:

  • 3 years stipend at UKRI rates. For 2021/2 this will be £15,609
  • 3 years tuition fees at the Home (UK) rates

Entry requirements

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject.  

The University of Leicester English language requirements apply where applicable.

Informal enquiries

Informal enquiries

Project / Funding Enquiries: jks43@leicester.ac.uk

Application enquiries to pgradmissions@le.ac.uk

How to apply

How to apply

To submit your application, please use the Apply button at the bottom of the page and select September 2021 from the dropdown menu.

With your application, please include:

  • CV

  • Personal statement explaining your interest in the project, your experience and why we should consider you

  • Degree Certificates and Transcripts of study already completed and if possible transcript to date of study currently being undertaken

  • Evidence of English language proficiency if applicable

  • In the reference section please enter the contact details of your two academic referees in the boxes provided or upload letters of reference if already available

  • In the funding section please specify that you wish to be considered for a MCB Panne 2021 studentship

  • In the research proposal section please provide the names of the project supervisors and project title (a research proposal is not required)

Eligibility

Eligibility

The PhD Studentship is open to UK/EU applicants only.