iPLACENTA Marie Skłodowska-Curie ITN Early Stage Researcher ESR8 - Epigenetic genome-wide investigation in patients with early/late-onset preeclampsia

INSERM Institut Cochin U1016 (Paris) and Université Paris-Descartes are looking for an Early Stage Researcher (ESR) with a focus on developing a personalized medicine analysis of preeclampsia. Preeclampsia (PE) is a pregnancy complication characterized by high blood pressure, proteinuria and in one third of the cases associated with intrauterine growth restriction (IUGR). In severe cases, kidney, liver, and brain can be affected, with long term consequences for the cardiovascular health of the mother and progeny.

About INSERM
INSERM (Institut National de la Santé et de la Recherche Médicale – French National Institute for Health and Medical Research) is the French Institute devoted to medical research. The Cochin Institute is a research unit of INSERM, grouping ~650 persons, inside which the team FGTB (From Gametes To Birth) focuses on human reproduction diseases. The Cochin Institute (https://www.institutcochin.fr/?set_language=en) uses 10 core facilities, allowing for the use of high throughput techniques, light imaging, electronic imaging, CrispR/cas9 models, etc.


Project description:
The project is part of iPlacenta (www.iplacenta.eu), a new European Union’s Horizon 2020 research and innovation programme ETN, to model the placenta for early detection of preeclampsia and intrauterine growth restriction, and to train the next generation of Translational Scientists for Maternal and Fetal Health.

The focus of the project is to analyse the methylation/hydroxymethylation status of a series of DNAs from placentas (Controls, Intra-Uterine Growth-Restriction – IUGR –, Mild Preeclampsia, Severe Preeclampsia with IUGR, Severe preeclampsia without IUGR), using methylation arrays (EPIC, Illumina), that provide information on >800,000 CpG of the human genome. This work will be performed in close connection with the ESR6 which will provide on the same placenta samples information about gene expression levels, and DNA polymorphisms.
This database constitution will be followed by the systematic identification of genes and regulatory elements that are pertinent to understand genome regulation in the context of placental diseases. The most significant genes (i.e. strongly deregulated and/or belonging to important gene networks for specific functions, will be further studied on cell models. In the lab, we generated cell models that can be considered as mimicking preeclampsia and placental diseases. The models are based on two different choriocarcinoma cell lines, the BeWo (analogous to villous trophoblast) and the JEG-3 (related to extravillous trophoblasts), permanently transformed with different versions of the STOX1 transcription factor Based upon the patient results, it will be straightforward to use the cells to analyse, characterize and/or demonstrate the effects of gene manipulation (inactivation/overexpression), and epigenetic manipulation (in vitro methylation of transfected plasmids, azacytidin treatment, trichostatin treatment) to assess the effects on gene expression and local methylation. The work will consist in cloning specific regions and evaluating their effect on the regulation of specific promoters, in interaction with specific transcription factors. A specific attention to imprinted gene deregulation will be given, following previous observations of our team and others on the impact of imprinted gene deregulation in the context of placental diseases.


Candidate profile:
- Interests in developing and translating technology to answer medical questions and solve healthcare problems in women health
- Strong understanding in Cell and Molecular Biology
- Good knowledge of bioinformatics, Epigenetics

- Able to communicate with scientists, engineers and clinicians of different disciplines;
- Have a motivated, flexible and positive work attitude;
- Proficiency in English language.
- be flexible to travel throughout the Europe in order to exchange expertise between the partners of iPLACENTA consortia

Eligibility:
To this position applies a mobility rule. The respective candidate must not have worked for more than 12 months in France within the last three years. Furthermore, the candidate needs to be in his/her first four years of his/her research career. The four years are counted from the date a degree was obtained which formally entitles to embark on a doctorate in the country either in the country in which the degree was obtained or in the country in which the research training is provided.

Starting date: 1st Sept 2018
Duration: 36 months

How to apply:
Submit an application to [Email Address Removed]
Application form can be downloaded from www.iplacenta.eu
Interviews by teleconference: June-July

Deadline for application:Monday 18th June 2018 (Midnight-GMT)