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Dissecting and modelling of a cell fate decision in yeast

  • Full or part time
    Dr F van Werven
  • Application Deadline
    Tuesday, November 12, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

This 4-year PhD studentship is offered in Dr Folkert van Werven’s Group based at the Francis Crick Institute (the Crick).

Alternative mRNA isoforms and long noncoding RNAs (lncRNA) and make up a large fraction of the transcriptome and play key functions in cell-fate programming. These transcripts often initiate upstream of coding gene promoters from alternative transcription start sites (TSS) where they can regulate gene expression in cis through transcription-coupled chromatin alterations. How, when and where transcription of alternative cis-acting RNAs regulates local gene expression remains poorly understood?

In my laboratory, we use budding yeast as a model for cell differentiation to study the usage of alternative transcripts. In particular, we use yeast gametogenesis or sporulation as a model [1]. Over the years, we have studied how alternative transcripts regulate local gene expression at single loci as well as genome-wide scale [2-4]. We have developed high-resolution quantitative approaches to study the alternative transcriptome. Recently, we identified thousand alternative TSSs are upregulated specifically during distinct cell fate transitions giving rise to long upstream mRNA isoforms or long noncoding RNAs. Importantly, transcription from alternative upstream TSSs is associated with different regulatory outcomes for the expression of canonical mRNAs. However, little is understood about why in some cases alternative transcripts lead to activation or repression of gene expression. The next challenge will be to dissect the mechanisms that mediate gene regulation by alternative transcripts.

Candidate background
We are interested in candidates with various backgrounds. Especially, candidates with backgrounds in molecular biology, biochemistry and genomics, but also computational biology would be suitable. The most important is that you have a strong curiosity towards basic sciences.

Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2020 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.

APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘APPLY NOW’ LINK ABOVE) BY 12:00 (NOON) 13 NOVEMBER 2019. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.

Funding Notes

Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.

References

1. van Werven, F. J. and Amon, A. (2011)

Regulation of entry into gametogenesis.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 366: 3521-3531. PubMed abstract

2. Chia, M., Tresenrider, A., Chen, J., Spedale, G., Jorgensen, V., Ünal, E. and van Werven, F. J. (2017)

Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter.

eLife 6: e27420. PubMed abstract

3. Moretto, F., Wood, N. E., Kelly, G., Doncic, A. and van Werven, F. J. (2018)

A regulatory circuit of two lncRNAs and a master regulator directs cell fate in yeast.

Nature Communications 9: 780. PubMed abstract

4. van Werven, F. J., Neuert, G., Hendrick, N., Lardenois, A., Buratowski, S., van Oudenaarden, A., . . . Amon, A. (2012)

Transcription of two long noncoding RNAs mediates mating-type control of gametogenesis in budding yeast.

Cell 150: 1170-1181. PubMed abstract

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