PhD studentship in Huntington's disease research (PhD Studentship)
Reference Number: R2210
Project title: Cells for Huntington’s disease: gene function in the neural differentiation program
We study neural differentiation, in particular the differentiation of medium spiny neurons (MSNs) of the striatum. Striatal MSNs are lost in the neurodegenerative disorder Huntington’s disease (HD). In the absence of a cure, one therapeutic approach is replacing the MSNs lost to the disease with new ones.
- MSNs can be derived from human fetal striatum, but this is a scarce resource, so we plan to differentiate MSNs from stem cells (SCs)
- However, it remains a major challenge to precisely and reliably direct the differentiation of SCs to MSNs.
Generating protocols to achieve this requires an in-depth understanding of the MSN differentiation program. As a step towards this, we conducted an expression screen for genes up-regulated during peak murine striatal development. One prominently up-regulated gene was Mef2c, which encodes a transcription factor with roles in the differentiation of a variety of cell-types3. These include roles in various aspects of neural differentiation from progenitor cells through to synapse formation.
To start understanding how Mef2c fulfils these different roles we have initiated a Y2H screen for interacting proteins. These potential novel regulators of Mef2c function will inform how its activity is regulated in progenitor cells and how it functions at different stages during the differentiation program. More generally, it will indicate how Mef2c activity is modulated in different cell differentiation programs. For conserved regulators, you will have the opportunity to adopt a “3Rs” approach to use Drosophila as a model system to explore hypotheses prior to testing in mice. We have also established a Mef2c conditional knock-out transgenic mouse model, and RNAi techniques to analyse gene function in differentiating primary cultures from developing striatum.
We anticipate that the project will aid progress in manipulating stem cell differentiation into MSNs in order to realise the potential of this approach to treating HD.
Start date: October 2014
Number of Studentships: 1
This studentship is generously funded by the Medical Research Council. This studentship consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£13,863 p.a. for 2014/15, updated each year).
One studentship is available.
Residency: Full awards (fees plus maintenance stipend) are open to UK Nationals and EU students who can satisfy UK residency requirements. To be eligible for the full award, EU Nationals must have been in the UK for at least 3 years prior to the start of the course for which they are seeking funding, including for the purposes of full-time education. EU Nationals who do not meet the above residency requirement are eligible for a fees only award, provided that they have been ordinarily resident in the EU for at least 3 years prior to the start of their proposed programme of study.
Academic criteria: Applicants for a studentship must have obtained, or be about to obtain, a 2.1 degree or higher in a relevant science-based subject.
How to Apply
Consideration is automatic on applying for PhD Bioscience, with a start date of October 2014 via Cardiff University's Online Application Service. In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description into the text box provided. In the funding section, please select "I will be applying for a scholarship / grant" and specify that you are applying for advertised funding from the Medical Research Council (MRC).In place of the personal statement, please explain why you want to undertake a research study (approx. 500 words).
The deadline for all applications is 14 February 2014.
Further information can be found via the Neuroscience research division webpages.
- Dunnett SB and Rosser AE (2011). Clinical translation of cell transplantation in the brain. Current Opinion in Transplantation 16(6):632-9.
- Kelly CM et al (2007). Fetal neural precursors yield more extensive efferent connections than primary fetal cells in both striatal allograft and striatal xenograft. Brain 130:1317-29.
- Elgar SJ, Han J and Taylor MV (2008) mef2 activity levels differentially regulate gene expression during Drosophila muscle development. PNAS 105:918-923.