Coventry University Featured PhD Programmes
King’s College London Featured PhD Programmes
University of Glasgow Featured PhD Programmes
University of Liverpool Featured PhD Programmes
Birkbeck, University of London Featured PhD Programmes

The mechanisms that link piRNA-guided transposon silencing with chromatin biology

  • Full or part time
  • Application Deadline
    Friday, April 12, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Eukaryotic genomes harbour a multitude of diverse transposon elements. These selfish genetic elements threaten genome integrity due to their potential to mobilise and insert into new genomic locations, causing DNA damage and disrupting essential genes. This is a particular problem in the germline, which must faithfully pass on genetic information to the next generation. As such, animals have evolved a sophisticated small RNA-based immune system, the PIWI-interacting (piRNA) pathway, that guards the genome of germ cells against transposable element activity. The piRNA pathway is centred on 23-30nt piRNAs and their protein partners, Argonaute proteins of the PIWI clade. PIWI proteins are guided by their bound piRNA to transposon targets which they silence via two mechanisms. Cytoplasmic PIWI proteins cleave transposon mRNAs directly via their slicer activity, so-called post-transcriptional gene silencing. Alternatively, some PIWI proteins, including Drosophila Piwi, translocate to the nucleus when loaded with a piRNA. Here, Piwi recognises nascent transposon transcripts and directs the deposition of repressive chromatin marks via recruitment of the general silencing machinery, so-called transcriptional gene silencing (TGS).

The Hannon lab aims to uncover the molecular mechanisms that underlie the piRNA pathway using the fruit fly Drosophila melanogaster as a model. We have recently identified a complex containing Panoramix, Nxf2 and Nxt1 that functions downstream of Piwi to direct TGS, however the upstream signals that allow Piwi to recruit this complex, and the downstream mechanism utilised by this complex to instrument the general silencing machinery are yet to be understood. This PhD project will investigate these questions using a combination of genomics (RNA-seq, ChIP-seq and small RNA-seq), proteomics, biochemistry, cell biology, imaging (super resolution and live cell imaging) and bioinformatics. Overall, this project will lie at the interface between small RNA-guided silencing and chromatin biology.

Preferred skills/knowledge
Applicants should have a relevant undergraduate degree and keen interest in working on this project. A strong background in biochemistry or cell biology as well as six months or more of lab experience is desirable. The successful candidate should be highly motivated to drive their project to a successful conclusion and demonstrate critical thinking and independency. They should have excellent communication skills and the ability to work effectively as a part of a diverse team.

Funding Notes

Funding
This project is funded by a studentship that includes full funding for University and College fees, a stipend of £19,000 per annum and a generous consumables allowance.

Eligibility
No nationality restrictions apply to this studentship. Applications are invited from recent graduates or final year undergraduates who hold or expect to gain a first/upper second class degree (or equivalent) in a relevant subject from any recognised university worldwide.

References

Czech B, et al. (2018). piRNA-Guided Genome Defense: From Biogenesis to Silencing. Annu Rev Genet 52, 131-157.

Sienski G, et al. (2012). Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell 151, 964-980.

Yu Y, et al. (2015). Panoramix enforces piRNA-dependent cotranscriptional silencing. Science 350, 339-342.

How good is research at University of Cambridge in Clinical Medicine?

FTE Category A staff submitted: 192.05

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully





FindAPhD. Copyright 2005-2019
All rights reserved.