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EASTBIO: Identifying molecular controls involved in limb development and limb length

  • Full or part time
    Prof Neil Vargesson
    Prof L Erskine
    Prof M Collinson
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Supervisors:

Professor Neil Vargesson (University of Aberdeen)
https://www.abdn.ac.uk/people/n.vargesson/

Professor Lynda Erskine (University of Aberdeen)
https://www.abdn.ac.uk/people/l.erskine

Professor Martin Collinson (University of Aberdeen)
https://www.abdn.ac.uk/ims/profiles/m.collinson

The development of the limbs is a complex process beginning with the outgrowth of cells from specific regions along the flank of the early embryo. These initial outgrowths, called limb buds, then develop into the fully functional limb complete with bones, nerves, muscle, tendons and blood vessels (Davey et al., 2018). What is even more remarkable is that the limbs all form independently of each other, yet both our arms and both legs are normally the same size and length. The mechanism/s underpinning the control of limb size, so that both arms and both legs are accurately matched is unclear. Understanding the molecular and morphological controls underpinning limb outgrowth and size control will provide information on normal development and may also shed light on the origins of limb malformations.

Previous work from the group has demonstrated that loss of blood vessels during limb development can cause a broad range of limb malformations, which include shortening of limbs, the severity of which is dependent on timing of blood vessel loss (Therapontos et al., 2009; Davey et al., 2018). Further work from our group has also found that nerve inhibition does not cause limb malformations but does cause shortening of the limbs and which also appears to be time dependent (Mahony et al., 2018). Yet, how loss of vessels or nerves result in differences in limb development and limb outgrowth are unclear as is the molecular basis of these differences.

This project will study i) the role of blood vessels and nerves in normal limb outgrowth and size control and ii) determine molecular changes following pharmacological inhibition of blood vessels and nerves that result in limb outgrowth and size differences. We will use RNA Sequencing to identify the molecular changes and targets which will also be analysed in-vivo through misexpression techniques including retroviral overexpression assays and gene loss strategies including RNAi and CRISPR-Cas9.

In summary, this project will identify the molecular targets and the molecular networks involved in limb outgrowth and size control. The student will learn embryology, pharmacological inhibition assays, molecular biology, imaging and gene misexpression skills.

Application Procedure:
http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts and CV to Alison McLeod at . Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to .

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. 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. Queries on eligibility? Email Alison McLeod ().

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

References

Davey MG, Towers M, Vargesson N, Tickle C. (2018). The chick limb: embryology, genetics and teratology. International Journal of Developmental Biology, 62: 85-95.

Mahony C, McMenemy S, Rafipay AJ, Beedie SL, Fraga LR, Gutschow M, Figg WD, Erskine L, Vargesson N. (2018). CPS49-induced neurotoxicity does not cause limb patterning anomalies in developeing chicken embryos. Journal of Anatomy, 232: 568-574.

Therapontos, C., Erskine, L., Gardner, E., Figg, W., Vargesson, N. (2009). Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation. Proceedings of the National Academy of Sciences, 106(21): 8573-8578.



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