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Modelling Neurocristopathies in Xenopus, mechanisms and drug screening (WHEELERGU19MCETN1)

  • Full or part time
  • Application Deadline
    Friday, October 18, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

NEUcrest is an Innovative Training Network (ITN) project, funded by the European Union Horizon 2020 Programme. The neural crest (NC) is an essential stem cell population of the vertebrate embryos that gives rise to various tissues in the body such as the cranial facial cartilage, peripheral nervous system and the Adrenal Medulla. NEUcrest focuses on integrating academic, clinical and industrial research for a better understanding of neural crest development and neural crest related diseases called Neurocristopathies. These pathologies are a major group of congenital diseases in human, and a heavy societal concern. The NEUcrest network comprises 20 partners in academia, industry and hospitals from seven European countries, gathered in a synergistic effort to advance knowledge and outreach about these diseases.

The adrenal gland is derived from NC and mesodermal lineages. Disorders of the adrenal glands can lead to congenital neuroendocrine anomalies, autoimmune disease, neurocristopathies and tumors such as neuroblastoma. The embryology of this organ has not been well-studied; therefore, it has been difficult to correlate developmental gene-function interactions and identify novel disease variants. In this project the student will:
1) determine a temporal and spatial map of the development of the adrenal gland during Xenopus embryogenesis including how the NC contributes to its development.
2) generate novel assays for gene discovery and function of diseases associated with the adrenal gland. Potential syndromes to look at include Allgrove syndrome and Von Hippel-Lindau syndrome. Assays will include gene knockdown by morpholino or CRISPR/Cas9 and measurement of adrenaline and noradrenaline levels.
3) carry out a small molecule enhancer/suppressor screen on an adrenal gland Xenopus model line generated by the student.

The student will gain skills in molecular biology, embryology, in vivo biology and chemical biology. In addition, training for transverse skills in outreach and industrial managements are deeply embedded in the ITN programme.

For more information on the supervisor of this project, please go here: https://people.uea.ac.uk/grant_wheeler

Type of programme: PhD
Start date: January 2020
Mode of study: Full-time

Requirements: Acceptable first degree in Biological Sciences, Cell Biology, Genetics, and Molecular Biology

Funding Notes

This project is awarded with a 3-year PhD scholarship through the Horizon 2020 Marie Skłodowska-Curie Actions - Innovative Training Networks (ITN) Programme (No. 860635, pending Grant Agreement Signature). EU applicants are eligible to apply who have not been based in the UK for more than 12 months in the last 3 years. Remuneration will be in line with the Marie Skłodowska-Curie guidelines (Early Stage Researchers, ITN). For programme, funding information and eligibility criteria please visit: View Website

Tuition fees are covered for UK/EU rate only (£4,327 2019/20 rate). A living salary will be provided for each year of the scholarship.

References

i) Hoppler S and Wheeler GN. (2015) It's about time for neural crest. Science, 348 (6241):1316-1317

ii) Nicole J Ward, Darrell Green, Janet Higgins, Tamas Dalmay, Andrea Münsterberg, Simon Moxon and Grant N Wheeler (2018). microRNAs associated with early neural crest development in Xenopus laevis. BMC Genomics, 19(1):59

iii) Victoria L. Hatch, Marta Marin-Barba, Simon Moxon, Christopher T. Ford, Nicole J. Ward, Matthew L. Tomlinson, Ines Desanlis, Adam E. Hendry, Saartje Hontelez, Ila van Kruijsbergen, Gert Jan C. Veenstra, Andrea E. Münsterberg and Grant N. Wheeler (2016). The Positive Transcriptional Elongation Factor (P-TEFb) is required for Neural Crest Specification. Developmental Biology, 416: 361-372

iv) White RM, Cech J, Ratanasirintrawoot S, Lin CY, Rahl PB, Burke CJ, Langdon E, Tomlinson ML, Mosher J, Kaufman C, Chen F, Long HK, Kramer M, Datta S, Neuberg D, Granter S, Young RA, Morrison S, Wheeler GN, Zon LI. (2011) DHODH modulates transcriptional elongation in the neural crest and melanoma. Nature. 471:518-22

v) Grant N. Wheeler and Andre Brandlii. Simple vertebrate models for chemical genetics and drug discovery screens: lessons from zebrafish and Xenopus. (2009) Dev Dyn. 238:1287-1308.

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