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PhD position in Molecular Biology - Epigenetic aspects of early life stress & associated resilience mechanisms

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In the field of  “Epigenetic aspects of early life stress & associated resilience mechanisms” the research group of Prof. Ulrich Zechner offers one PhD project.

Using a multidisciplinary approach combining the above described mouse model of ELS with RNA, epigenetic and electrophysiological analyses, we aim to characterize the epigenetic basis of the molecular ELS response and possible pharmacological interventions.

Goal 1: Transcriptome and targeted epigenetic analysis in the the hypothalamus (periventricular nucleus, PVN), nucleus accumbens (NAcc) and hippocampus (dentate gyrus, DG) of ELS versus control mice
We will determine the transcriptome (using RNA-Seq) of neuron-enriched PVN, NAcc and DG cell preparations and single neuronal cells with the Illumina HiSeq 2500 system to identify genes, alternative splice isoforms and noncoding RNAs (e.g., miRNA, lncRNAs) differentially expressed between ELS versus control mice (P18-26) of either sex. Differentially expressed genes will be bioinformatically evaluated and categorized for (neuro)-biochemical pathways. RNA-Seq results will be validated by RT-qPCR. DEGs will be further analysed for epigenetic markers (DNA methylation and hydroxymethylation, histone methylation and acetylation) in neuron-enriched cell preparations to determine a potential epigenetic basis for the observed expression differences, using Chromatin Immunoprecipitation (ChIP)-qPCR as well as bisulfite and oxidative bisulfite pyrosequencing and amplicon sequencing, respectively.

Goal 2: Pharmacological interventions of ELS-induced epigenetic processes followed by electrophysiological, transcriptome and epigenetic analyses
ELS and control mice will be treated at P10 with epigenetic drugs (in particular antidepressants), which target histone modification pathways (histone methylation and histone acetylation). Vehicle-treated control groups will be included. Following drug treatment, mice will be analyzed for electrophysiological properties. Subsequently, group differences in gene expression will be determined by RNA-Seq as well as RT-qPCR and related to the presence of specific epigenetic marks (DNA methylation and hydroxymethylation, histone methylation and acetylation) as in Goal 1.

We offer
•    The possibility to work on a cutting-edge project using state-of-the-art technology in a highly motivated research team
•    A stimulating, diverse and international research environment
•    Advanced training opportunities
•    A competitive stipend

Required qualifications
•    Master or Diploma
•    Motivation to solve complex biological problems
•    Excellent communication skills

Starting date: October 2015 or later
Duration of stipend: 3 years, with the possibility of extension
Deadline for registration (exclusively online via web form):  20 June 2015


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Details der Stellenanzeige

Befristete Anstellung
Berufserfahrung nicht vorausgesetzt
Deutschland (Rheinland-Pfalz)
55128 Mainz
Biologie & Life Sciences, Pharma