Funded PhD project in Jouy en Josas
Context:
Pluripotent Stem Cells (PSCs) are characterized by their extensive differentiation potential both in vivo and in vitro. They can be obtained by culturing early embryo (ES cells) or by reprogramming of somatic cells (iPS cells). Until recently, PSCs could only be established from rodent or primate embryos and the molecular reasons for the inability to derive PSCs in other species remain poorly understood. One possibility is that these cells carry inappropriate epigenetic marks which limit their pluripotency or that the signaling pathways known to activate the pluripotency network in mice and humans are inactive or insufficient in pigs. Recently, we and other laboratories have performed cell-single transcriptomics (scRNA-seq) studies at different embryonic stages. These new data help to identify the different states of pluripotency of embryonic cells and the signaling pathways that control them. Thanks to a recently funded ANR project (PluS4Pig, 2020-2024) that we are coordinating, we will be able to enrich these existing data sets with new expression, chromatin accessibility (scATAC-seq) and proteomics data. The objective of the project is to use technologies specific to big data to integrate these different biological dimensions in order to predict and then experimentally validate the optimal culture conditions for the expansion of porcine PSCs. The analysis of heterogeneous omics data at the level of the single cell meets the challenges of big data: In fact, we analyze thousands of individuals (cells) for thousands of heterogeneous variables (gene expression, chromatin accessibility, proteome).
The PhD project:
The PhD student will contribute to the prediction and characterization of the different states of pluripotency existing in the pig embryo through in silico analyzes of multi-omic single-cell data. He / she will:
1) characterize the embryonic molecular micro-environment and the gene networks controlling endogenous pluripotency
2) predict the signaling molecules necessary and sufficient for the maintenance of porcine pluripotent lines in vitro
3) disseminate the knowledge acquired on big data analysis to breeding companies in order to anticipate the phenotyping needs on health traits as well as the associated digital tools.
The first two objectives will be coordinated by the academic partner while the third objective will be coordinated by the socio-economic partner IFIP-Institut du Porc.
This project is funded by a collaborative ANR project (PluS4PiGs) which covered all the experimental costs necessary to complete the PhD project. The doctoral student will benefit from an efficient storage and computing infrastructure (http://bioinfo.genotoul.fr/). The PhD student will also benefit from the support of a bioinformatics engineer funded by the ANR project and fully dedicated to single-cell studies. The PhD contract is co-funded by the region Ile de France, the animal genetics division from INRAE and the IFIP-Institut du Porc. The latter will fund trainings dedicated to bioinformatics and single-cell studies to the PhD student as well as one international congress. It will also host the PhD student for dissemination and information activities as well as for writing the thesis manuscript, facilitating interactions with data analysts and statisticians of IFIP. The PhD student will benefit from a solid network of national and international collaborators, specialized in biostatistics and machine learning, bioinformatics and proteomics but also concerning the biological model and the pig sector. The main supervisor of the PhD student (70% supervision rate) has expertise shared between development biology, cell biology and animal genomics and will facilitate the connections between data and biological issues to meet the objectives of the project.
Activities:
This project is mostly focused on data analysis but also includes an experimental part. It will give the selected student a solid expertise for the analysis of single-cell omics data but also in mammalian embryology and cellular biology (culture of pig embryos and pluripotent stem cells and their molecular characterization).
Necessary skills:
A Master degree in bioinformatics/biostatistics or a dual competence in developmental biology/system biology will be favored. Intermediate level in R and Python is required.
Application process:
This project can be joined directly as a PhD student in fall/winter 2020. Funding is for 3 years.
Applications can be made to Hervé Acloque (herve.acloque@inrae.fr).
A more detailed version of the project is available here: https://www.dropbox.com/preview/Public/IdF_AAP_PhD_project_en.pdf
