PhD position in bioinformatics and artificial intelligence to study tumor cell plasticity (M/F)

Job Description

Thesis Subject

Summary

Tumor cell plasticity, i.e. the ability of tumor cells to switch between transcriptional states in response to intrinsic or environmental signals, plays a major role in tumor progression and treatment resistance. Understanding the molecular mechanisms governing these transitions therefore represents an important challenge in oncology.
This PhD project aims to develop and apply bioinformatics and artificial intelligence approaches to identify gene regulatory networks (GRNs) involved in tumor cell plasticity using single-cell transcriptomic data. The project will primarily focus on pancreatic ductal adenocarcinoma (PDAC), for which we have developed an integrated scRNA-seq atlas comprising more than one million cells from over 200 patients.
The project will combine conventional GRN inference methods, such as SCENIC, with recent approaches based on foundation models for single-cell data. Multimodal data, particularly epigenomic data, will also be integrated to refine the inferred networks and improve the identification of regulators associated with transitions between tumor cell states.


Specific objectives :
- Identify regulatory programs associated with tumor cell plasticity. Using our PDAC single-cell atlas, the project will investigate transcriptional programs and transcription factors associated with the continuum between classical, intermediate and basal-like tumor states. Foundation model-based approaches will be compared with conventional GRN inference methods and with previously identified regulators.
- Integrate multimodal data to refine GRNs. Publicly available complementary datasets, particularly chromatin accessibility and other epigenomic data, will be integrated with transcriptomic data to provide additional biological evidence for inferred regulatory relationships and prioritize candidate regulators of tumor cell plasticity.
- Assess the generalizability of the developed approaches to other tumor contexts. Methods developed in PDAC may be applied to other cancers with distinct plasticity landscapes to assess their ability to characterize intermediate tumor states and their underlying regulatory programs.

This PhD project will be carried out within AIMPACT, which develops artificial intelligence approaches to characterize and predict tumor cell plasticity by combining gene regulatory networks, spatial transcriptomics and predictive modeling. The PhD student will directly contribute to AIMPACT activities on single-cell GRN inference and will also participate in the organization of the project's scientific data challenges.

Your Work Environment

The Institute of Genetics and Development of Rennes (IGDR; CNRS UMR6290) is a biological research institute located on the health campus of the University of Rennes. With approximately 200 members, the IGDR develops innovative and multidisciplinary approaches to better understand the fundamental mechanisms governing cell division, identity and plasticity. Its research notably relies on approaches at the interface of biology, mathematics, physics and computer science.
The PhD will be primarily conducted within the emerging BINGO team at the IGDR, which develops bioinformatics and statistical approaches for the analysis of complex genomic and transcriptomic data in cancer research. The project will also benefit from the expertise of the @OMICs team (OSS, INSERM) and AIMPACT consortium partners in artificial intelligence and modeling.
The PhD will be supervised by Yuna Blum and Thomas Derrien (emerging BINGO team, IGDR, CNRS) and Myriam Bontonou (@OMICs team, OSS, INSERM). The project will also benefit from regular interactions with Magali Richard (LIG, UGA, CNRS), with whom Yuna Blum coordinates the AIMPACT project.
The project will be conducted in Rennes, on the Villejean campus, and will benefit from local computing and data-storage infrastructures, including the GenOuest and Eskemm bioinformatics platforms.

Constraints and risks

None

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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