FindAPhD Weekly PhD Newsletter | JOIN NOW FindAPhD Weekly PhD Newsletter | JOIN NOW

How does the nucleolus safeguard ribosome production during meiosis?


   Biosciences Institute

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Dr C Schneider, Dr U McClurg  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

How does the nucleolus safeguard ribosome production during meiosis?

Sexual reproduction relies on accurate meiosis, the unique cell division process which creates sperm and egg. All meiotic cells must maintain ribosomal (r)DNA integrity to avoid infertility, miscarriages and birth defects, but it is unclear how this is accomplished in mammalian cells or why the process becomes more error-prone at a later age. Importantly, the ever-increasing average age of first-time parents in developed countries calls for research into these questions to empower the identification of new targets for clinical intervention.

To allow for fertility and occurrence of novel traits, meiosis facilitates large-scale genome rearrangements during gametogenesis. This is achieved by the meiosis-specific synaptonemal complex (SC), which aligns homologous chromosomes. However, highly repetitive DNA elements like ribosomal (r)RNA genes, which are arranged in arrays with hundreds of rDNA units in tandem, pose a substantial risk to genome stability during meiosis since they can undergo nonallelic exchanges.

Unsupervised rDNA recombination during meiosis would result in faulty ribosomes compromising protein synthesis and consequently fertility. Initiated by rDNA transcription in the nucleolus, ribosome assembly follows an intricate and energy-consuming pathway involving hundreds of factors, including pre-ribosomal RNA cleavage enzymes that enable stepwise processing of the mature rRNAs from a precursor transcript. While rDNA arrays are transcriptionally active in the early stages of meiosis in plants, which appears to shield them from nonallelic recombination in the nucleolus, we don’t know if ribosome assembly commences in mammalian meiotic cells and/or which point(s) in the pathway are triggered to stop pre-ribosomal RNA processing to avoid energy waste or mistakes.

This PhD project based at Newcastle with a placement in Liverpool will involve a unique breath of training in complementary approaches (biochemistry, cell biology, human cell culture, mouse models, proteomic and state-of-the-art imaging techniques) to investigate the mechanisms by which mammalian cells may regulate ribosome production to protect their rDNA loci from nonallelic exchanges during meiosis.

This project is suited to students who need flexible working arrangements, and we welcome applications from minority backgrounds. A broad range of inter-disciplinary approaches will encourage innovative thinking and develop diverse technical expertise. Furthermore, this multi-disciplinary training will give the student a broad range of skills allowing them a wide choice of career options, both within and outside of academia, after the PhD.

For more information see https://www.ncl.ac.uk/medical-sciences/people/profile/claudiaschneider; https://www.mcclurglab.com; Twitter: @CSchneiderNCL; @CBCC_NCL; @UrszulaMcclurg.

Please contact [Email Address Removed] for an informal chat about the project.

The studentship should be commenced before the end of 2022.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with:

·        a CV (including contact details of at least two academic (or other relevant) referees);

·         a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply

The closing date for applications is Friday 8th July 2022 at 12noon (UK time).


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. Note that home (UK) candidates may also apply to this studentship.

References

2016: The PIN domain endonuclease Utp24 cleaves pre-ribosomal RNA at two coupled sites in yeast and humans. Nucleic Acids Res., https://doi.org/10.1093/nar/gkw213.
2017: The ribosome biogenesis factor yUtp23/hUTP23 coordinates key interactions in the yeast and human pre-40S particle and hUTP23 contains an essential PIN domain. Nucleic Acids Res., https://doi.org/10.1093/nar/gkw1344.
2018: Turnover of aberrant pre-40S pre-ribosomal particles is initiated by a novel endonucleolytic decay pathway. Nucleic Acids Res., https://doi.org/10.1093/nar/gky116.
2020: A pseudo-meiotic centrosomal function of TEX12 in cancer. BioRxiv, https://doi.org/10.1101/509869. In press in Communications Biology.
2020: Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability, Nature Communications, https://doi.org/10.1038/s41467-020-18306-x.
Search Suggestions
Search suggestions

Based on your current searches we recommend the following search filters.

PhD saved successfully
View saved PhDs