PlasticPhase - Micro and Nanoplastics as Modulators of Phase Separation and Protein Aggregation

PRISM programme

The PRISM (PhD Research Programme for International Training in Sustainable Soft Matter) programme has launched its first call for applications, offering up to 14 fully funded PhD fellowships starting from 1 March 2027 at Paris Sciences & Lettres (PSL) University. The programme trains researchers to address ecological transition challenges through sustainable soft matter science, with projects focused on eco-friendly chemical processes, circular economy, renewable energies, and carbon capture, storage, and valorisation. Co-funded by the European Union under Horizon Europe MSCA COFUND (Grant Agreement 101261637) and partner institutions, PRISM provides interdisciplinary, international, and intersectoral training, including mobility opportunities, secondments, and courses in sustainability, innovation, entrepreneurship, career development, and transferable skills.

Applications must be submitted via the PRISM website by 31 October 2026 (23:59 Paris time).                                                                    

The PhD project

Micro- and nanoplastics (MNPs) are tiny plastic particles originating from the breakdown of larger plastic waste. Due to increasing water and soil pollution, they are ubiquitous in the environment, raising concerns about their impact on human health. They can interact with biomolecular condensates which are subcellular compartments confining proteins and nucleic acids organizing cellular biochemistry in space and time. Condensate formation is often mediated through multivalent interactions between biomolecules leading to liquid-liquid phase separation (LLPS). Recent studies hypothesized that LLPS-derived condensates might represent intermediates in the path yielding toxic protein aggregates present in neurodegenerative diseases.

This project aims at investigating how MNPs interacts with biocondensates. The central hypothesis is that MNPs affect intracellular phase behavior via two interconnected mechanisms: (i) direct physicochemical interactions, where particles serve as heterogeneous nucleation sites or modify intermolecular interactions, and (ii) indirect effects mediated by stress-response pathways and proteostasis imbalance. These perturbations may drive biomolecular condensates from dynamic, reversible liquid states toward persistent, solid-like assemblies associated with pathological aggregation.

Capitalizing AIV team’sexpertise, we will construct model condensates that assemble through LLPS using engineered protein scaffolds, such as multivalent protein domain prone to homodimerize. These synthetic systems mimic the properties of natural condensates, including nucleation, growth, and fusion, allowing for controlled observation in both test tubes and living cells. Additionally, the project will examine UBQLN2, a disease-relevant protein that forms condensates transitioning into stress granules under oxidative or proteotoxic stress, serving as a model for pathological aggregation.

In parallel, we will generate a tunable library of MNPs with controlled size, charge, and surface chemistry to systematically investigate their effects on phase separation. Polystyrene nanoparticles of different sizes will serve as model MNPs. These particles can be modified by PEGylation, enabling control over surface interactions and colloidal stability. In addition, particles based on other polymers (e.g., PMMA, PE, PLA,…) will be prepared using nanoprecipitation, a technique mastered at AIV, to represent the diversity of MNPs in the environment.

This library will be tested against the synthetic condensates to quantify how specific MNP characteristics influence nucleation rates, growth dynamics, and condensate properties using advanced biophysical techniques. In vitro, researchers will monitor real-time nucleation and coarsening to determine if MNPs lower energy barriers for phase separation. In cellulo, live-cell imaging and Fluorescence Recovery After Photobleaching (FRAP) will measure molecular exchange rates and viscosity, assessing whether MNPs trap condensates in a solid state. Microrheology will further characterize the viscoelastic changes in the cytoplasm induced by particle exposure.

By comparing in vitro results, where cellular stress pathways are absent, with cellular data, the study seeks to disentangle direct physical effects from indirect stress responses.

Ultimately, this research aims to provide a predictive framework for understanding how environmental plastics contribute to neurodegenerative pathology. By identifying key determinants of MNP-condensate interactions, the project could reveal new risk factors for diseases like ALS and Alzheimer's, highlighting the urgent need to understand the molecular consequences of plastic pollution on human health.

3i dimensions

INTERNATIONAL: In the field of phase separation, we have several international collaborations that could be relevant for the PhD project. For instance, Z.G (AIV Team) start collaborating with Cláudio M. Gomes, at the University of Lisboa (Portugal), that has strong expertise in protein aggregation biophysics, proteostasis, and amyloid systems.

INTERSECTORAL: Z.G (AIV Team) has a collaboration with Sanofi on the topic of phase separation of proteins involved in neurodegenerative diseases (IDEA Tech awards Sanofi-PSL, 2022). With PSL Valo, we have a submitted a patent “Cell model of TDP-43 proteinopathy” (Europe, n°25306208.7) in 2025.

INTERDISCIPLINARY: Our work brings together experts in in chemistry (polymeric nano/micro-particles), physics/biophysics (soft matter, phase transition), and biology (protein biochemistry), which is essential for studying how environmental pollutants interact with fundamental biological processes.

References:

L. Sixdenier, A. Augé, Y. Zhao, E. Marie, C. Tribet, ACS Macro Lett. 2022, 11, 5, 651–656.

L. Piroska, A. Fenyi, S.Thomas, M-A. Plamont, V. Redeker, R.Melki, Z. Gueroui Z Science Adv. 2023, 9, eadg5663.

H. Merceron, … E. Marie-Bègue, L. Thouin, and L. Jullien, Adv. Sci. 2025, 12, e10903

Salary

The PRISM programme offers a competitive salary above the national average for PhD candidates in France to attract and support excellent researchers.

Doctoral candidates will receive an approximate net monthly salary of €2,200, with additional family and mobility allowances available for eligible fellows.

The salary is subject to French income tax, with the exception of the family and mobility allowances. Depending on the candidate's individual tax situation, income tax may represent approximately 2–5% of the net salary and is levied by the French tax authorities independently of the employer.

To ensure consistent management and equal employment conditions across the programme, all PRISM doctoral candidates will be employed by ESPCI Paris, regardless of the host laboratory where their research is carried out.

Employer’s benefits

Remote working opportunities, access to sports and leisure activities, free access to public Paris city council’s swimming pools, access to CROUS canteen, scientific campus in central Paris, professional development programs, well-being workshops, social benefits through CNAS, partial health insurance support, and 75% support for sustainable mobility.

Name of the school of PSL

ENS - PSL (Ecole Normale Supérieure)

Research Unit

CPCV UMR8228

To address the project, the consortium combines expertise in synthetic biology, polymer chemistry, and biophysics to employ a multiscale approach, bridging in vitro reconstitution with cellular models. AIV Team (CPCV): E. MARIE has extensive experience in polymer and colloidal sciences (particle formulation, surface modification) and in the physical chemistry of responsive polymers. Z.Gueroui pioneered in studying phase separation using synthetic biology and has strong experience in investigating stress-response-driven LLPS, particularly in the context of pathological condensates and aggregation (TDP-43 and alpha-synuclein) and RNA-protein condensates (stress-granules and p-bodies). QPC team (Curie): D.Cuvelier has a long-standing experience in developing novel tools to study biological systems, cell biophysics, combining soft matter and quantitative physical chemistry. In particular, GEMS has been already introduced in the lab to study the microenvironment of the cytoplasm and nucleoplasm under cell confinement.

Supervision

Supervisor: Emmanuelle MARIE emmanuelle.marie@ens.psl.eu and Zoher Gueroui zoher.gueroui@ens.psl.eu (AIV Team, CPCV, UMR 8228)

Co-supervisor: Damien Cuvelier Damien.Cuvelier@curie.fr (QPC team, Curie: Quantitave Physiology of the Cell)

Candidates are encouraged to contact the project supervisors to discuss the proposed research topics before applying. All projects are open PhD projects, meaning that the research plan will be further developed collaboratively by the selected doctoral candidate and the supervisors.

We are looking for a highly motivated and intellectually curious candidate with a strong background in soft matter and a deep interest in biological systems. The candidate should be trained in the theoretical and experimental foundations of complex fluids, colloids, to understand the physical principles governing out-of-equilibrium and mesoscale systems. She/he should be motivated to explore the application of physical concepts and methods to biological questions.

We are looking for someone with a genuine interdisciplinary mindset, combining quantitative rigor with a strong willingness to engage with biological complexity. She/he should be enthusiastic about learning new experimental approaches relevant to biophysics and comfortable working at the interface between physics and biology. Their profile is characterized by scientific curiosity, adaptability, and a strong motivation to contribute to collaborative, cross-disciplinary research environments.