M/F PhD Position - Effects of nanoplastics on mammary tumorigenesis and its progression: a multi-scale physicochemical and oncobiological investigation

Job Description

Thesis Subject

Breast cancer is the leading cause of cancer-related mortality among women in France, with over 60,000 new cases and 12,000 deaths recorded annually (INCa, 2023). While genetic risk factors are now well characterized, elucidating the contribution of environmental factors has become an urgent priority. Concurrently, the ubiquitous contamination of ecosystems and the human body by plastic particles constitutes one of the most pressing environmental crises of our era. The degradation of macro-plastic waste now permeates the human exposome in the form of micro- and nanoplastic particles (NPPs), raising critical questions regarding their potential role as environmental co-factors or catalysts in the etiology of chronic diseases, including cancer.

The scientific community has established that plastic particles are not inert pollutants: they can induce cytotoxicity, oxidative stress, and chronic inflammation — three fundamental pillars of carcinogenesis. Recent studies have demonstrated that polystyrene nanoplastics are significantly internalized by human mammary epithelial cells, impairing both their proliferative capacity and migratory behavior. More alarmingly, exposure to polypropylene microplastics appears to dysregulate the expression of cell cycle-related genes and to promote the acquisition of metastatic features in breast cancer cells. Despite these advances, the specific role of plastic nanoparticles as potential triggers of the metastatic cascade in mammary tissue remains largely unexplored.

This knowledge gap is further compounded by methodological limitations inherent to existing studies: current exposure models are often overly simplistic (single-polymer, short-term exposure) and fail to adequately characterize the behavior and dynamics of NPPs within relevant biological fluids. The ONCOPLAST project, funded by the Mission for Cross-Disciplinary and Interdisciplinary Initiatives of the CNRS (MITI), was designed to address these shortcomings by investigating the potential causal relationship between the physicochemical complexity of the nanoplastic exposome and mammary tumorigenesis — from tumor initiation to metastatic progression. This research is grounded in the One Health framework, which acknowledges the profound interdependence between environmental pollution and human health.

The interdisciplinary ONCOPLAST project, within which this doctoral position is embedded, will investigate the health impact of nanoplastic pollution on breast cancer development. At the interface of colloidal physical-chemistry and cell biology, it will examine how the properties of common plastic nanoparticles — including composition, surface functionality, size, and aggregation state — modulate the response of both healthy and cancerous human mammary cells. A central objective will be to determine whether such exposure generates toxic effects and/or triggers the epithelial-to-mesenchymal transition (EMT), a process by which sedentary epithelial cells acquire invasive properties that promote the metastatic cascade. Combining high-resolution fluorescence photonic imaging with phenotypic analyses of metastatic behavior, this project will quantify the oncogenic cocktail effects of the nanoplastic exposome, from the (sub)cellular to the cell population scale. This research is framed within the One Health vision, deciphering the links between environmental pollution and the etiology of human pathologies in order to inform public health strategies. Further details regarding the ONCOPLAST project and the profile of the prospective doctoral candidate are available at https://duvaljfl.webnode.fr/available-positions/

Your Work Environment

As part of the research activities detailed below, the doctoral candidate's missions will include: (1) conducting cell culture experiments, performing nanoplastic exposure assays, carrying out phenotypic screening of nanoplastic-exposed cells, and executing transcriptomic analyses; (2) contributing to experiments aimed at characterizing the physicochemical properties of the plastic exposome; (4) participating in the characterization of (sub)cellular responses by fluorescence microscopy — with certain type of experiments to be performed independently following appropriate training; and (5) conducting mechanistic analyses of the data in order to decode the mode of action of NPPs in the context of mammary tumorigenesis.
The doctoral research program is structured around two integrated research axes:
Axis 1: Colloidal Physicochemistry of the Nanoplastic Exposome
Mechanistic interpretation of the biological effects induced by NPPs requires prior quantitative knowledge of their physicochemical behavior in biologically relevant media. This axis is dedicated to the characterization of mono- and multi-polymer NPP suspensions — comprising polyethylene (PE), polystyrene (PS), and polypropylene (PP) — under conditions representative of real-world exposome scenarios. The doctoral candidate will quantify the kinetics of homo- and heteroaggregation, as well as sedimentation dynamics in biological fluids, using dynamic light scattering (DLS) and laser diffraction granulometry, alongside the surface properties of the particles — notably their electrokinetic charge, hydrophobic/hydrophilic balance, and surface chemical composition (FTIR). These parameters collectively govern the effective dose of NPPs delivered to the adherent cell monolayer and will determine the magnitude of the biological responses investigated in Axis 2.

Axis 2: Phenotypic, Functional, and Molecular Responses of Mammary Cells to NPP Cocktails
Building upon the data generated in Axis 1, this second axis aims to determine how the complexity of NPP mixtures modulates the malignant potential of three complementary mammary cell models: healthy epithelial MCF-10A cells, non-invasive tumor MCF-7 cells, and highly invasive MDA-MB-231 cells. A macroscopic phenotypic screening — encompassing proliferation, cell death, senescence, and migration/invasion assays across early, acute, and chronic exposure time courses — will identify the most biologically relevant conditions for higher-resolution investigations. At the subcellular scale, laser scanning confocal fluorescence microscopy (CLSM) and spectral fluorescence lifetime imaging microscopy (spectral FLIM) will enable spatial mapping of the intracellular distribution of NPP aggregates, various stress parameters, and EMT markers. Finally, transcriptomic analyses will establish the molecular signatures of NPP exposure and identify the signaling pathways underlying EMT induction, thereby providing evidence for a potential causal link between nanoplastic contamination and mammary tumorigenesis.

The doctoral candidate will serve as the operational cornerstone of the ONCOPLAST project, bridging the complementary expertise of physical-chemists and cell biologists. Within a collaborative and dynamic consortium, the candidate will benefit from active, day-to-day support from researchers and technical staff across the two laboratories involved in the project: the Laboratoire Interdisciplinaire des Environments Continentaux (LIEC, UMR 7360 CNRS, Physical-chemistry and Reactivity of Surfaces and Interfaces Research Group - PhySI), Vandœuvre-lès-Nancy, France, and the Centre de Recherche en Automatique de Nancy (CRAN, UMR 7039 CNRS, BioSiS Research Team — Liquid Biopsies and Therapeutic Optimization), Université de Lorraine, Nancy, France.
Drawing on a solid background in cell biology, the doctoral candidate will lead the phenotypic screening and identification of critical nanoplastic exposure conditions leading to the modulation of viability and migration/invasion capacity across three cell models representative of the progression of mammary pathology: healthy epithelial cells, non-invasive tumor cells, and invasive cancer cells. The candidate will conduct the transcriptomic analyses required to validate the molecular signatures associated with tumor progression. Alongside this biological expertise, the candidate will receive comprehensive training in fluorescence photonic techniques to be employed in decoding (sub)cellular responses to nanoplastic stress, progressively acquiring proficiency in routine confocal microscopy (CLSM) and developing mastery of spectral FLIM (fluorescence lifetime imaging microscopy) — a technique providing an intrinsic biophysical signature of fluorescence sources and their microenvironment.
The candidate will also be introduced to the physicochemical experiments of Axis 1 of the ONCOPLAST project, aimed at qualifying and quantifying the colloidal stability of plastic nanoparticles in the biological fluids of interest. This training will be delivered through targeted sessions within the LIEC team. This transdisciplinary immersion will equip the doctoral candidate with an integrated understanding of the project — spanning from the characterization of colloidal interfaces to the mechanisms of the metastatic cascade — and will constitute a decisive asset for a future career in academic research or industrial R&D.

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.

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