Cardiff School of Biosciences PhD Studentship: Determining the role of extracellular calcium in stem cell neurogenesis and differentiation (PhD Studentship)
Reference Number: R1020
Key Studentship Information
Project Title: Determining the role of extracellular calcium in stem cell neurogenesis and differentiation
Consistent and reproducible specification of functional neurons from human pluripotent stem cells is crucial to the development of cellular models of neurological disease both for accurate disease modeling and for the development of reliable high-throughput drug screening programmes. This is especially true in understanding and treating several neurodegenerative disorders such as Huntington’s Disease (HD) and Parkinson’s disease (PD) where there is already significant knowledge about which neuronal populations within the central nervous system are initially at risk of cell death. Central to the disease modeling process is the ability both to specify particular neuronal populations, such as mid-brain dopaminergic neurons (for PD) or striatal medium spiny neurons (for HD) and for them to demonstrate key electrophysiological characteristics of mature neurons. Recently, we have developed a differentiation protocol for induced pluripotent stem (iPS) cells derived from HD patients which generates functionally active neurons with many phenotypic hallmarks of HD (The HD iPSC Consortium et al., 2012). Furthermore, we have shown that neuronal maturation is accelerated by a number of experimental manoeuvres, including increasing extracellular Ca2+ concentration (Rushton et al., submitted), consistent with a role for either Ca2+ channels or extracellular Ca2+-sensing receptor (CaSR) in neuronal maturation and synaptogenesis; importantly, CaSR has been shown to control neurite outgrowth and target innervation in vivo (Vizard et al. 2008).
In this project, you will generate neurons from human embryonic stem (ES) cells and iPS cells derived from unaffected and HD patients in order to investigate the mechanism(s) by which increased extracellular Ca2+ concentration leads to functional maturation of stem cell-derived neurons, testing the hypothesis that neuronal maturation and synaptogenesis are accelerated by Ca2+-dependent transcriptional events. The project will combine state-of–the-art stem cell imaging and electrophysiology to investigate neural maturation and will employ several novel techniques including longitudinal studies to determine the rate and extent of maturation using chameleon-based FRET probes and novel fluorescent differentiation markers. Ca2+-dependent transcriptional regulation will focus initially on CREB, a known target of Ca2+ regulated transcription in synaptogenesis and plasticity and then move on to determine how immediate-early and long-term changes in the neuronal transcriptional profiles are correlated with functional neuronal phenotypes. Thus, at the close of the project, you will have determined the detailed molecular and cellular determinants of Ca2+ dependent maturation of stem cell-derived neurons in order to model better important neurodegenerative disorders such as Huntington’s Disease.
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 Prof. Paul Kemp (Kemp@cardiff.ac.uk). Complete the application forms or online application forms, selecting Biosciences as the host department and using “Determining the role of extracellular calcium in stem cell neurogenesis and differentiation” as the research project title.
Application Deadline: 4th March 2013