Cardiff School of Biosciences PhD Studentship - Cells for Huntington’s disease: gene function in the neural differentiation program
Reference Number: R1023
Key Studentship Information
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 ones1. MSNs can be derived from human fetal striatum, but this is a scarce resource, so we plan to differentiate MSNs from stem cells (SCs)2. 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. This is the goal of this project. 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. You will analyse these potential novel regulators of Mef2c to inform how Mef2c functions at different stages during the differentiation program. For conserved regulators, you will have the opportunity to adopt a “3Rs” approach to use Drosophila as a model system to explore hypotheses for the regulation of Mef2 activity 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. You will be able to exploit both approaches. 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.
1. Rosser AE, Zietlow R, Dunnett SB. Stem cell transplantation for neurodegenerative diseases. Current opinions in Neurology (2007) 20(6):688-692.
2. Evans AE, Kelly CM, Precious SV, and Rosser AE. Molecular regulation of striatal development. Anat Res Int. (2012) ;2012:106529.
3. Elgar SJ, Han J and Taylor MV. Mef2 activity levels differentially regulate gene expression during Drosophila muscle development. PNAS (2008) 105:918-923.
Start Date: 1st October 2013
Number of Awards Available: 1
This studentship will commence in October 2013 and will cover UK/EU tuition fees and Doctoral stipend of £13,726 p.a.
Academic Criteria: The equivalent of a undergraduate degree at level 2:1 (or higher) in a relevant biological, biomedical or bio-molecular science subject.
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.
English Language Requirement: GCSE/IGCSE grade C or above or IELTS with an overall score of 6.5 and a minimum score of 5.5 in each skill area (or equivalent qualification).
How to Apply
For further details on the project contact Professor Anne Rosser(RosserAE@cardiff.ac.uk). Please complete an online application through our Online Application Service, selecting Biosciences as the host department and using “Cells for Huntington’s disease: gene function in the neural differentiation program” as the research project title.
Application Deadline: 4th March 2013