Don't miss our weekly PhD newsletter | Sign up now Don't miss our weekly PhD newsletter | Sign up now

  White Rose BBSRC DTP: How can we identify variants in untranslated RNA that affect stem-cells


   Yorkshire Bioscience Doctoral Training Partnership

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 Ian Sudbery, Prof Ivana Barbaric, Prof Stuart Wilson  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Most DNA sequence variation between individuals is found in non-coding sequence. However, determining which variants might have functional effects is difficult outside protein coding regions. One such region that is largely overlooked is the Untranslated Regions of protein coding transcripts (UTRs). 3’ UTRs bind miRNAs, which regulate transcript stability and translation. However, we cannot currently predict variants will or will not effect how miRNAs regulate gene expression. 

miRNAs are particularly important in the regulation of stem cell pluripotency and differentiation. This project will measure the effects of sequence changes on both miRNA binding and activity in induced pluripotent stem cells, and build models to test hypotheses about the connections between these. 

In this project the student will use cutting edge functional genomics, sequencing, bioinformatics and statistical tools to measure how changes in miRNA levels and target site sequences change miRNA regulation genome-wide. 

This project will mix wet and dry biological research, and the student will receive a through training in both lab and bioinformatics/data science techniques and might suit students from a broad range of biological, statistical and computational backgrounds who are eager to learn interdisciplinary skills.

About the DTP

This studentship is offered as part of the White Rose BBSRC Doctoral Training Partnership (DTP) in Mechanistic Biology, which brings together the research of the world-class molecular and cellular bioscience centres at the White Rose universities of Leeds, Sheffield and York.

Our mission is to train excellent bio-scientists who understand how living systems work and can innovate to address global challenges, such as the impact of climate change, a healthier old age, sustainable food production, land use and energy production.

What is on offer?

This is a core studentship for entry in October 2024.  

Join us and you will receive a 4-year, funded PhD programme of research and skills training, with cross-disciplinary supervision, plus a structured programme of cohort-wide training and networking events. A highlight is the annual symposium, which is planned and delivered by students.

A unique part of your training will be the Professional Internships for PhD Students (PIPS), where you will spend three months at a host organisation of your choosing, gaining experience of work in a professional environment, and acquiring transferable skills that will be beneficial in your future career.

How to apply – Expression of Interest

Students may apply for up to three projects anywhere in the Doctoral Training Partnership (DTP).  Applications will be to the DTP centrally, using an online Expression of Interest (EoI). The EoI will include:

§ CV information; not submitted separately

§ Equality, Diversity and Inclusion (EDI) data

§ Names of two referees

Deadline for EoIs is midnight Sunday 7th January 2024.

Submit EoIs using this link: https://leeds.onlinesurveys.ac.uk/white-rose-bbsrc-dtp-expression-of-interest-form

Shortlisted candidates will be required to make formal applications to the Graduate School at each institution, supplying the necessary paperwork.

Interviews will be held either Friday 2nd and Monday 5th to Friday 9th February, or Monday 19th to Friday 23rd and Monday 26th February 2024, in-person at Leeds, Sheffield and York, with a panel representing all 3 Universities. Shortlisted candidates will be notified of a specific time/date to attend. If you have applied for more than one project and are selected for interview, you will be interviewed only once. 

Website: https://www.whiterose-mechanisticbiology-dtp.ac.uk/

Biological Sciences (4)

Funding Notes

Appointed candidates will be fully funded for 4 years:
 Tax-free annual stipend at the UKRI rate. The rate for starters in 2023/24 was £18,622. (Rates for 2024/25 starters are not yet available).
 UKRI tuition fees – These are paid directly to the host institution.
 A Research Training and Support Grant
 An allowance for Fieldwork/Conference/Travel
 A Professional Internship for PhD Students (PIPS) allowance
Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.

References

N Viphakone*, IM Sudbery*, C Heath, D Sims, SA Wilson. “Co-transcriptional loading of RNA export factors shapes the human transcriptome.”, Mol Cell 2019, 75(2):310-323.e8
Cribbs AP, Luna-Valero S, George C, Sudbery IM, Berlanga-Taylor AJ, Sansom SN, Smith T, Ilott NE, Johnson J, Scaber J, Brown K, Sims D, Heger A, “CGAT-core: a python framework for building scalable, reproducible computational biology workflows”, F1000Research 2019 8:377
Niespolo, C., Johnston, J.M., Deshmukh, S.R., Satam, S., Shologu, Z., Villacanas, O., Sudbery, I.M., Wilson, H.L., Kiss-Toth, E.§, TRAIN Consortium. “Tribbles-1 Expression and Its Function to Control Inflammatory Cytokines, Including Interleukin-8 Levels are Regulated by miRNAs in Macrophages and Prostate Cancer Cells” Front. Immuno. 2020, 11,. 574046.
Ray, S.; Abugable, A. A.*; Parker, J.*; Liversidge, K.; Palminha, N. M.; Liao, C.; Acosta-Martin, A. E.; Souza, C. D. S.; Jurga, M.; Sudbery, I.; El-Khamisy, S. F. “A mechanism for oxidative damage repair at gene regulatory elements”, Nature 2022, 609:1038-1047
Vitillo L, Anjum F, Hewitt Z, Stavish D, Laing O, Baker D, Barbaric I, Coffey P (2023) The isochromosome 20q abnormality of pluripotent cells interrupts germ layer differentiation. Stem Cell Reports 18(3):782-797.
Pernaute B, Sánchez Nieto J.M, Pérez-Montero S, di Gregorio A, Lima A, Lawlor K, Bowling S, Liccardi G, Tomás A, Meier P, Rutter GA, Barbaric I, Rodríguez T (2022) DRP1-mediated regulation of mitophagy determines the apoptotic response upon embryonic differentiation. Developmental Cell 57(11):1316-1330.e7.
Price CJ, Stavish D, Gokhale PJ, Stevenson BA, Sargeant S, Lacey J, Rodriguez TA, Barbaric I (2021) Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition. Developmental Cell 56:2455-70.
Halliwell JA, Baker D, Judge K, Quail MA, Oliver K, Betteridge E, Skelton J, Andrews PW, Barbaric I (2021) Nanopore sequencing indicates that tandem amplification of chromosome 20q11.21 in human pluripotent stem cells is driven by break-induced replication. Stem Cells and Development 30(11):578-86.
N Viphakone*, IM Sudbery*, C Heath, D Sims, Wilson, S.A. “Co-transcriptional loading of RNA export factors shapes the human transcriptome.”, Mol Cell (2019), 75(2):310-323.e8
Lesbirel, S., Viphakone, N., Parker, M., Parker, J., Heath, C., Sudbery, I. and Wilson, S.A. (2018) The m6A-methylase complex recruits TREX and regulates mRNA export. Scientific Reports 8:13827 (41 citations)
Baquero-Perez, B., Antanaviciute, A., Yonchev, I.D, Carr. I., Wilson, S.A., Whitehouse, A. (2019) The Tudor SND1 protein is an m6A reader essential for KSHV replication. eLIFE 2019;8:e47261
Manners, O., Baquero-Perez, B., Mottram, T.J., Yonchev, I., Trevelyan, CJ., Harper, KL., Patterson, MR., Macdonalad, A., Wilson, S.A., Aspden, J., Whitehouse, A. (2023) m6A regulates the stability of cellular transcripts for efficient KSHV lytic infection. Viruses 15:1381