Post-doc – mechanisms of 3D genome organization (Gif-sur-Yvette/Paris-area, France)

Summary:

A funded postdoc position is available in the team of Daan Noordermeer at the Institute for Integrative Biology of the Cell (University Paris-Saclay, France). The project aims to determine how genomic clustering of CTCF binding improves the structure and function of TADs (Topologically Associating Domains), using a mix of innovative multi-contact 3C technology (Nano-C), super-resolution microscopy and genome editing approaches.

The project:

3D genome organization is an essential determinant of genome function. Mammalian chromosomes are compartmentalized into TADs (Topologically Associating Domains) that demarcate functional neighborhoods for gene regulation and DNA repair, replication and recombination [1,2]. The Noordermeer team has made important contributions to our understanding of structure/function relationships of 3D genome organization (see [3-6] for recent examples).

Recent studies have emphasized the importance of TAD boundaries for gene regulation [2,7,8]. Binding of the CTCF insulator protein is strongly enriched at TAD boundaries, where it helps to structure TADs by blocking the loop extrusion function of the Cohesin complex [1,9]. We have recently identified a complex pattern of clustering of binding sites for the CTCF insulator protein at TAD boundaries [4]. How this clustered CTCF binding improves the blocking of loop extrusion and the functionality of TADs remains incompletely characterized.

Using our recently developed Nano-C assay, a multi-contact Chromosome Conformation Capture assay that incorporates Nanopore sequencing, we can quantitatively study the blocking of loop extrusion at TAD boundaries [4]. In this project, funded by the French National Research Agency (ANR), we will combine Nano-C with super-resolution imaging (oligopainting, collaboration with Eric Joyce, University of Pennsylvania) to precisely dissect how the loop extrusion machinery interacts with clusters of CTCF binding sites and other blocking elements. For this purpose, we will use mouse embryonic stem cells where clusters of CTCF binding are perturbed (genome editing) and/or where key proteins are depleted (CTCF, Cohesin components). The role of the candidate will be to perform genomics and imaging experiments and assist with data analysis.

The candidate:

We are looking for an excellent and motivated candidate with a passion for chromatin biology and cutting-edge genomics and imaging technology. We are looking for a team player that can collaborate with both experimentalists and computational biologists.

The candidate should have a PhD in molecular biology or biochemistry with a focus on chromatin biology and a proven record of academic excellence. Experience with genomics technologies and data analysis is a plus.

The team:

The Noordermeer team is an international and multi-disciplinary group of 7 people, with both wet-lab and computational biology expertise. The team has direct and prioritized access to state-of-the-art genomics technology (Oxford Nanopore MinION and GridION, Illumina Next-seq 2000), imaging (I2BC imaging platform) and the I2BC computational infrastructure (CPU and GPU computing). The working language in the Noordermeer team is English.

Team website

The institute:

The Institute for Integrative Biology of the Cell (I2BC) is among the largest French academic research centers in molecular and structural biology (650 people) and is located in Gif-sur-Yvette (France, Paris area). The institute mixes experimental and computational research groups and has several state-of-the-art technology platforms, including genomics and imaging. The institute is part of the University Paris-Saclay, a world-class university in the natural and life sciences.

The I2BC is located in Gif-sur-Yvette, in the green Chevreuse Valley, 20 km south of Paris. Gif-sur-Yvette has a direct metro connection with Paris (RER B line, 30 minutes) and is located near the Paris-Orly airport and high-speed TGV train connections (Massy TGV train station). The Chevreuse Valley combines possibilities for a wide variety of outdoor activities (rock climbing, cycling, running) with access to the world-class infrastructure and cultural activities of the Paris metropole.

I2BC website

University Paris-Saclay website

Employment:

The postdoctoral position is for 1 year (fulltime), with possibility for 1 year renewal. Postdoctoral fellows will be encouraged to apply for independent funding. The salary is according to standard CNRS remuneration. The salary includes pension benefits and health insurance. The latest start date is December 2022, at which time candidates need to have passed their PhD defense.

How to apply:

Applications should be sent through the CNRS recruitment portal (see link).

Candidates should include a CV with a statement of research interests and contact details for at 2 references.

Requests for information should be directed to Daan Noordermeer .

Interviews will start immediately and will continue until the position is filled. International candidates and candidates who are interested in obtaining a permanent position within the French research system (CNRS or INSERM concours) are highly encouraged to apply.

Selected references:

1. Dixon JR, et al. (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature; 485:376-80.

2. Chang L-H*, Ghosh S* and Noordermeer D (2020) TADs and their borders: free movement or building a wall? Journal of Molecular Biology; 432:643-652.

3. Chang L-H*, Ghosh S*, et al. (2021) A complex CTCF binding code defines TAD boundary structure and function. BioRxiv; https://www.biorxiv.org/content/10.1101/2021.04.15.440007v1

4. Moniot-Perron L, et al. (2022) The Drosophila Fab-7 boundary element modulates Abd-B gene activity by guiding inversed collinear chromatin structure and alternative promoter use. BioRxiv; https://www.biorxiv.org/content/10.1101/2022.04.26.489596v1

5. Arnould C, et al. (2021) Loop extrusion as a mechanism for DNA Double-Strand Breaks repair foci formation. Nature; 590:660-665.

6. Llères D*, Moindrot B*, Pathak R*, et al. (2019) CTCF controls imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains by modulating allele-specific sub-TAD structure. Genome Biology; 20:272.

7. Zuin J, et al. (2022) Nonlinear control of transcription through enhancer-promoter interactions. Nature; 604:571-577.

8. Gabriele M, et al. (2022) Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging. Science; 376:496-501.

9. Fudenberg G, et al. (2016) Formation of Chromosomal Domains by Loop Extrusion. Cell Reports; 15:2038-2049.

* Equal first-author contribution.