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*EASTBIO* Modelling telomere length dynamics in a multicellular organism.

  • Full or part time
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

BBSRC Thematic Group: Health
Telomeres are protective structures that cap the ends of linear chromosomes. At their core, telomeres are formed from hundreds to thousands of repeats of a consensus telomeric DNA sequence. The end replication problem causes telomeric DNA to be lost every cell cycle. Once telomeres reach a critically short threshold they trigger a DNA-damage response that prevents further cell division or results in programmed cell death. Cells that require indefinite replicative capacity must extend telomeres, and can employ either telomerase or the alternative lengthening of telomeres (ALT) pathway. There is great medical interest (cancer, liver disease etc.) in understanding both telomere maintenance mechanisms.

Methods to measure telomere length accurately are key to understanding these telomere maintenance mechanisms. However, there are a number of challenges: 1) The repetitive nature of telomeric DNA presents challenges to analysis via high-resolution techniques such as DNA sequencing and 2) Telomeres are heterogeneous in length and current techniques are low resolution and tend to report the average length. Having access to accurate information about the distribution of all individual telomere lengths is crucial because it is the shortest individual telomere rather than the average telomere length that triggers stress responses such as inhibition of cell division.

This project will build on work from the Lynch group (Farmery et al 2018) to combine different next generation DNA sequencing technologies (Illumina and Nanopore). This will allow us to follow all individual telomere lengths with high accuracy in an animal system (C. elegans). Importantly, C. elegans is the only known animal model where one can study both telomerase dependent and independent (ALT) telomere maintenance pathways during development [Lackner et al 2012]. These data (in combination with, e.g., single-cell RNAseq data) will be used to build a model of telomere length dynamics during development and how it is influenced by different telomere length mechanisms.

Telomere shortening is an important anti-cancer mechanism. Overcoming the limits placed on cellular mortality and thus enabling replicative immortality is a recognized hallmark of cancers. Cancer cells can prevent telomere shortening via either telomerase or the alternative lengthening of telomeres (ALT) pathway and we will look to bring new interpretation to the results of cancer telomere studies through application of our results.

As appropriate to their background, the student will receive broad training in statistics and machine learning or biology, while also having access to the University of St Andrews award-winning GRADskills programme. Specific to this project, the student will receive training in areas including telomere biology, C. elegans genetics and the generation and analysis of next-generation sequencing data. They will develop skills in presenting oral and written work to audiences from different disciplines, as well as having many opportunities to take part in outreach events.

Funding Notes

This project is eligible for the EASTBIO Doctoral Training Partnership: View Website

This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body.

Apply by 5.00 pm on 5 January 2020 following the instructions on how to apply at: View Website

Please also upload the EASTBO Application Form as an additional document to the University of St Andrews online Application.

Informal inquiries to the primary supervisor are very strongly encouraged.

References

Farmery et al. (2018). Telomerecat: A Ploidy-Agnostic Method For Estimating Telomere Length From Whole Genome Sequencing Data. Scientific Reports 8, 1300

Lackner et al. (2012). Organismal propagation in the absence of a functional telomerase pathway in Caenorhabditis elegans. EMBO J. 31:2024–2033

How good is research at University of St Andrews in Biological Sciences?

FTE Category A staff submitted: 50.45

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

Click here to see the results for all UK universities

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