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The molecular mechanisms of piRNA biogenesis.

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

Project Description

The Hannon laboratory has a long-standing interest in small RNA biology. In recent years, the lab has focused on the study of the PIWI-interacting RNAs (piRNAs) in Drosophila melanogaster. The piRNA pathway is an RNA-based immune system that protects the germline of animals from uncontrolled transposon mobilisation, thus safeguarding genome integrity. Our lab has pioneered this field, being amongst the first describing the pathway, carrying out large-scale genomic screens to identify the main players and characterising their role within the pathway.

The project aims at understanding the molecular mechanisms that drive the biogenesis of piRNAs. While a rough framework of piRNA processing has been established, the precise hierarchy of the processing events and the exact role of each factor is not yet fully understood. This aim will be achieved by combining biochemistry, high-throughput approaches (RNA-seq, small RNA-seq, CLIP-seq, proteomics), super-resolution (live) cell imaging and computational approaches by exploiting in vitro cell culture models and fly genetics. Understanding how piRNAs are generated will bring substantial advancements to the field and will be crucial to understand how the piRNA pathway can adapt and evolve to achieve robust transposon control.

Preferred skills/knowledge
Applicants should have a relevant undergraduate degree and a strong interest in working on RNA biology research. Ideal candidates should have a reasonable amount of lab experience in biochemistry and/or molecular biology, with further experience in bioinformatics being desirable. The successful candidate should be highly motivated, capable of independent thought, have excellent communication skills and the ability to work collaboratively.

Funding Notes

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.

Czech B, Preall JB et al. (2013) A transcriptome-wide RNAi screen in the Drosophila ovary reveals factors of the germline piRNA pathway. Mol Cell 50, 749-761.

Ipsaro JJ, Haase AD et al. (2012) The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature 491, 279-283.

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

FTE Category A staff submitted: 192.05

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