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Selective processes on regulatory elements and their turnover in the chiken genome

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  • Full or part time
    Prof Burt
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

Background
Action of negative selection can indicate functional regions in genomes and can be detected in two
ways. First, by studying the genome over a broad phylogeny of species and looking for regions which
show reduced level of divergence1. Second, within population of a single species, by looking into
reduced level of polymorphism. Using the first approach we identified 1.5 million selectively
constrained regions in the chicken genome which are likely to be functional. Some of these regions have
regulatory function1,2 (e.g. transcription factor binding sites, enhancers or insulators) and define the
expression-level and complexity of the transcriptome. Despite the functional significance regulatory
annotation is missing for birds and studies in mammals3 indicate that many of these elements undergo
rapid turnover.

Project
The main focus of this project is to estimate turnover of regulatory regions (RR) in chicken and compare
this with what was observed for mammals by using comparative genomics and population genetics. By
looking into a set of RRs identified by CAGE and ChIP-seq experiments (e.g. CTCF) both within and
outside selectively constrained regions we try to address the following questions:
Can the function of RRs be verified in-vivo?
Is there a quantitative difference in the downstream effect of RRs as a function of constraint?
How does existing or artificial variation affect the regulatory capacity of RRs (both in natural
populations and in-vitro)?
Is there evidence for selection within RRs from polymorphism data?
Does the strength of selection on RRs correlate between divergence and polymorphism based estimates?
Is the dynamic of turnover of RRs in birds different from that of mammals?

Training
Expected:

Population and Quantitative Genetics (UoE)

Additional-bioinformatics:

Introduction to Python for Biologists (Edinburgh Genomomics – EG)
Introduction to variant analysis of NGS data (EG)
Unix (UoE)
Statistics

Transferable skills courses (IAD, UoE)

Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be sent to: Liz Archibald, The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG or emailed to [email protected]

When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.

When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.

All applicants should also apply through the University’s on-line application system for September 2016 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=830

International students should also apply for an Edinburgh Global Research Studentship (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/international/global/research).


ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 1st FEBRUARY 2016

References

Lindblad-Toh K, Garber M, Zuk O et al.: A high-resolution map of human evolutionary constraint using 29 mammals. Nature 2011, 478:476–482.

Andersson R, Gebhard C, Miguel-Escalada I et al.: An atlas of active enhancers across human cell types and tissues. Nature 2014, 507:455–461.

Villar D, Berthelot C, Aldridge S, Rayner TF, Lukk M, Pignatelli M, Park TJ, Deaville R, Erichsen JT, JasinskaAJ, Turner JMA, Bertelsen MF, Murchison EP, Flicek P, Odom DT: Enhancer Evolution across 20 MammalianSpecies. Cell 2015, 160:554–566.

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