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Analysing the role of FGF signalling in pluripotency and skeletalmuscle development.


Project Description

During development, totipotent stem cells give rise to a host of
specialised, differentiated cell types. This process involves the
progressive restriction of developmental potential, and requires the highly
coordinated activation of sets of regulatory genes in specific groups of
cells in the developing embryo in response to cell signalling. The
fibroblast growth factor (FGF) signalling pathway is an important
regulator of gene expression during development. Our previous work
indicates that FGF signalling activates and maintains the expression of
key developmental regulators, such as the transcription factor MyoD; a
myogenic regulatory factor that can orchestrate the process of
differentiation of skeletal muscle cells from stem cells. During vertebrate
development skeletal muscle cells arise from a pool of stem cells in the
posterior of the developing embryo. Recent evidence indicates that
properties of stem cells are regulated by a number of pluripotency
factors, including Oct4, c-Myc, Lin28, and Nanog. This project will
investigate the interplay of FGF signalling, MyoD and pluripotency factors
in muscle development in vivo using non-mammalian vertebrate animal
models (Xenopus and zebrafish).
This project will take make use of the advantages of frog and fish
embryos for investigating cell lineage, cell signalling and gene expression

during development. We will make use CRISPR/Cas9 mediated gene
editing in frogs and fish to investigate the role of the FGF signalling and
the pluripotency factors c-Myc, Lin28, and Vent2 (nanog) in skeletal
muscle development. Manipulating the FGF signalling using
pharmacological inhibition to inactivate and inducible FGF receptors to
overstimulate the pathway will be the initial approach to uncovering the
regulation of muscle determination, maintenance and differentiation
during development. The student will also undertake some
embryological manipulations of frogs embryos to determine the
pluripotent nature of the cells in the posterior mesoderm.

Funding Notes

Funding: This is a 4 year fully-funded studentship part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology. The studentship covers: (i) a tax-free stipend at the standard Research Council rate (around £15,000 per year), (ii) tuition fees at UK/EU rate, (iii) research consumables and training necessary for the project.

Entry requirements: At least an upper second class honours degree, or equivalent in any biological, chemical, and/or physical science. Students with mathematical backgrounds who are interested in using their skills in addressing biological questions are also welcome to apply.

References

Eligibility: The studentships are available to UK and EU students who meet the UK residency requirements. Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award. Further information about eligibility for Research Council UK funding

Shortlisting: Applicants will be notified if they have been selected for interview in the week commencing on Monday 28 January 2019.

Interviews: Shortlisted applicants will be invited for an interview to take place in the Department of Biology at the University of York on Wednesday 6 and Thursday 7 February 2019. Prior to the interview candidates will be asked to give a 5 minute presentation on a research project carried out by them.

How good is research at University of York in Biological Sciences?

FTE Category A staff submitted: 44.37

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

Click here to see the results for all UK universities

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