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PhD project - Investigation of the impact of personalized differences, sampling and storage conditions on the reprogrammability and neuronal differentiation of human fibroblasts

This is a joint project between the Developmental and Cellular Biology Group at LCSB (http://wwwen.uni.lu/lcsb/research/developmental_and_cellular_biology) and the Integrated Biobank of Luxembourg (http://www.ibbl.lu/). The selected candidate needs to apply for a national fellowship (application deadline in September 2014), if successful a start in January 2015 is envisaged.

Project description:
Parkinson’s disease (PD) is an age associated progressive neurodegenerative disease. The main characteristic of PD is the degeneration of dopaminergic neurons in the substantia nigra. Although the aetiology of PD is not completely understood, currently 18 gene loci have been linked to PD. However, the majority of PD cases seem to be idiopathic, with no single mutation known to cause the pathogenesis. However, a recent study suggested that in cases of
idiopathic PD the disease causing susceptibility must also be encoded in the genome of these patients. Consequently, stem cells predisposed to PD are an important tool to in vitro model the disease. In the past, human PD-patient specific iPSCs and neurons have been generated and some clear and expected defects, such as increased susceptibility to oxidative stress occur in the patient specific dopaminergic neurons. Other defects that have been described are a reduced neurite complexity as well as nuclear-architecture defects. Interestingly, one of these studies clearly showed that neurons derived from idiopathic patients show defects similar to those derived from patients with mutations in LRRK2. Obviously, there is some progress in iPSC derived cell based in vitro disease modelling. Nevertheless, there is a clear lack of research addressing the effect of personalized differences, sampling and storage of human fibroblasts and the impact of these effects on following analysis approaches like in vitro modelling of disease processes. In this project we aim on addressing this lack.

The working hypothesis are:
  • Several factors influence the reprogrammability of human fibroblasts into iPSCs.
  • Quality parameters in fibroblasts allow to predict the reprogrammability of fibroblasts.
  • Quality parameters, measured already in fibroblasts, allow to predict the ability of fibroblast derived iPSCs to differentiate into dopaminergic neurons.

  • All these parameters are measurable in a quantitative manner. Therefore, it will be possible to correlate parameters measured in fibroblasts with the efficiency of reprogramming and the ability of reprogrammed cells to differentiate into dopaminergic neurons. For addressing these hypothesis we will use human fibroblasts from healthy individuals and sporadic Parkinson’s disease patients. These fibroblasts will be reprogrammed into iPSCs and these will be differentiated into dopaminergic neurons. All steps will be accompanied by several quality control analysis methods.

    Please send your application by end of August to: jens.schwamborn@uni.lu

    Contact detail

    How to apply:
    Email: jens.schwamborn@uni.lu
    Send application to
    Prof. Jens C. Schwamborn
    Developmental and Cellular Biology
    Luxembourg Centre for Systems Biomedicine (LCSB)
    University of Luxembourg
    7, avenue des Hauts-Fourneaux
    L-4362 Esch-sur-Alzette
    Tel: +352-466644-5536 (office)
    Tel: +352-691-450810 (mobile)
    Email: jens.schwamborn@uni.lu
    Website: http://wwwen.uni.lu/lcsb/research/developmental_and_cellular_biology

    Job profile

    Working hours
    Contract duration
    Type of job
    PhD Project
    Work experience
    job experience is not required
    Working place
    4362 Esch-sur-Alzette
    Area of expertise
    Biology & Life Sciences, Biotechnology, Human medicine