3D reconstruction of chromatin conformation by super-resolution microscopy

ESRIC PhD Programme:

This is one of four projects being offered in 2016 for one three-year PhD studentship available in the Edinburgh Super-resolution Imaging Consortium (ESRIC), aiming to apply state-of-the-art microscopy techniques to investigate cellular function and human disease. ESRIC is one of the most comprehensively equipped super-resolution Centres of Excellence in Europe, with state-of-the-art systems alongside a broad range of expertise across the scientific spectrum. This is an exciting opportunity to work at the cutting edge of biological imaging at the molecular scale with access to the latest technology. Appropriate multi-disciplinary supervision will be provided.

Project description:
Long range gene regulation occurs over large genomic distances and over these distances, enhancers must seek-out and find their target promoters. The expression of the sonic hedgehog (Shh) gene is controlled by a cis-regulatory domain consisting of over 1 million basepairs. This regulatory domain is responsible for the differential expression of Shh during embryonic development. The conformation of the chromatin within this regulatory domain is a key component of the enhancer/promoter interactions that drive this gene expression.

This project will use super-resolution microscopy to visualize changes in chromatin conformation in different activity states in the embryo. STORM (stochastic optical reconstruction microscopy) with serial ultrathin sectioning for large-volume reconstruction of endogenous molecular targets in tissues will be used. Resolution of these enhancer/promoter interactions in the range of 50-100nm will enable investigation of structures that are predicted by biochemical analysis. This project aims to further develop STORM as a tool for investigating sub-nuclear structure and requires collaboration with computational biologists to develop the serial array tomography techniques for the high resolution 3D reconstructions.

Who should apply:
The Edinburgh Super-Resolution Imaging Consortium PhD programme is highly multi-disciplinary, attracting students with a diverse range of backgrounds including first degrees in STEM subjects (biology, biochemistry, genetics, chemistry, physics, and engineering).

How to Apply:
Applicants should hold at least an upper second class degree or equivalent in a related subject. Applicants should submit a personal statement about your research interests, reasons for applying and a C.V. before 28 February to [Email Address Removed].

Applicants must also submit an online application, to our PhD programme via EUCLID following the instructions at http://www.igmm.ed.ac.uk/students/recruitment/
We will not consider applications that have not been submitted to both [Email Address Removed] and EUCLID by the closing date.

If you have not heard from us by 7 March please consider your application unsuccessful (we will not be able to provide feedback on unsuccessful applications).

Shortlisted candidates will be invited to attend interview in early April. General enquiries can be made to: [Email Address Removed] and further information and eligibility requirements are available at http://www.igmm.ed.ac.uk/students/

Eligibility:
This funded studentship is open only to UK students, or EU students if they have been studying in the UK for the previous 3 years or working in a related discipline in the UK. EU students coming from a discipline related to super-resolution imaging are also eligible to apply.

Further information:
http://www.esric.org/
https://www.hgu.mrc.ac.uk/
http://www.igmm.ac.uk