Chemical biology approaches to rare earth toxicology in Humans
Recent technological developments have expanded and intensified the use of lanthanides in domains as diverse as renewable energy, computing, and medicine. Increasing usage of these metals raises the question of their impact on the environment and human health. However, the potential toxicity of these metal ions, and its underlying molecular mechanisms, are still little known and rarely investigated in human cell models. The goal of the PhD will be to investigate the human cells response to exposure to Ln ions, and to systematically identify the proteins involved in this response, using a set of chemical and biological tools. In particular, we want to address the following questions: which protein networks are activated or deactivated following Ln exposure? Do Ln ions affect phosphorylation of proteins? Which proteins are directly interacting with Ln ions? will thus decipher what are the key biological interactors of lanthanides, their roles in living systems and the features that enable efficient binding to metals. We expect that our findings will give insights into the toxicology of those elements and inform environmental and occupational safety policies. On the longer term, new bio-inspired strategies for their extraction, recycling, decorporation and remediation will arise from the molecular understanding of metal-life interactions, enabling a well thought-out usage of these elements to support the environmental and numerical transitions.s
Mapping surface potentials of catalytically activated metal oxide photoanodes
During photoelectrolysis (or solar water splitting), charge transfer at the photoanode / electrolyte interface is determined by the alignment between energy bands, both at the electrode and electrolyte side. Surface potential of the electrode plays a major role on the final band bending and thus charge separation at the interface. Also called electrochemical surface potential, it varies as a function of material environment (vacuum, air, water, etc.). The objective of this thesis is to address the OER (Oxygen Evolution Reaction) at the photoanode / electrolyte interface in terms of energy bands and in particular from the electrochemical surface potential perspective. Thus, during this thesis the student will characterize surface potentials of a series of catalytically activated metal oxide photoanodes in contact with different environments (vacuum, variable humidity air, water) and correlate it to photoelectrochemical activity. PhD student’s activity will be structured around fours axes: i) synthesis of photoanodes; ii) photoelectrochemical activity characterization; iii) characterization by atomic force microscopy (AFM) correlated with Kelvin force microscopy (KPFM); iv) synchrotron X-ray spectromicroscopies (STXM, XPEEM) and near ambient pressure photoemission (NAP-XPS). The student will be hosted at the SPEC laboratory at CEA-Saclay for the duration of the thesis. HisHer work is part of a long-standing collaboration between SPEC and SOLEIL.
Combination of ionizing radiation and radio-enhancing molecules in breast cancer models
The proposed program aims to evaluate the efficacy of molecules enhancing the effects of radiotherapy, in models of breast cancer. Several molecules targeting and inhibiting the Base Excision Repair pathway will be tested for radiopotentiation efficacy in the in vitro and in vivo models.
The proposed inhibitors are already being investigated in vitro, both in the laboratory and by collaborators. We have shown that inhibition of the mechanisms targeted leads to an impairment in DNA damage repair following genotoxic stress. During this project, we will evaluate the effects of inhibitors on DNA damage repair induced by irradiation of different types (conventional, ultra-high dose rate, even extreme dose rate) and the associated mechanisms.
Variability in response to therapeutic combinations is frequently observed when moving from in vitro to in vivo models. We will therefore evaluate the inhibitors on cell line models well characterized in the laboratory, and corresponding to different breast cancer subtypes. On the other hand, the studies will be completed by a validation of the effects observed in vitro on a murine model of breast cancer. This xenograft model, developed in immunocompetent animals, will enable us to monitor the clinical, histological and immune response of the animals and their tumors, in order to confirm the interest of the molecules for therapeutic application in support of radiotherapy.
The proposed program will benefit from the laboratory's collaborations with physicists and chemists, and IRCM's experimental facilities and platforms (irradiation, animal experimentation, microscopy, cytometry, etc.).
Precision measurements of neutrino oscillations and search for CP violation with the T2K and Hyper-Kamiokande experiments
The study of neutrino oscillations has entered a precision era, driven by long-baseline experiments like T2K, which compare neutrino signals at near and far detectors to probe key parameters, including possible Charge-Parity Violation (CPV). Detecting CPV in neutrinos could help explain the Universe’s matter–antimatter asymmetry. T2K’s 2020 results gave first hints of CPV but remain limited by statistics. To improve sensitivity, T2K has undergone major upgrades: replacing the most upstream part of its near detector with a new target, increased accelerator power (up to 800 kW by 2025, aiming for 1.3 MW by 2030). The next-generation Hyper-Kamiokande (Hyper-K) experiment, starting in 2028, will reuse the T2K beam and near detector but with new far detector 8.4 times larger than Super-Kamiokande greatly boosting the statistics. The IRFU group has key role in the near detector upgrade and is now focusing on analysis, crucial for controlling systematic uncertainties crucial for the Hyper-K high statistics time. The proposed PhD work centers on analyzing the new near detector data: designing new sample selections taking into account for the low-momentum protons and neutrons from neutrinos, and refining neutrino–nucleus interaction models to improve energy reconstruction. The second goal is to propagate these improvements to Hyper-K, guiding future oscillation analyses. The student will also contribute to Hyper-K construction and calibration (electronics testing at CERN, installation in Japan).
Axion searches in the SuperDAWA experiment with superconducting magnets and microwave radiometry
Axions are hypothetical particles that could both explain a fundamental problem in strong interactions (the conservation of CP symmetry in QCD) and account for a significant fraction of dark matter. Their direct detection is therefore a key challenge in both particle physics and cosmology.
The SuperDAWA experiment, currently under construction at CEA Saclay, uses superconducting magnets and a microwave radiometer placed inside a cryogenic cryostat. This setup aims to convert potential axions into measurable radio waves, with frequencies directly linked to the axion mass.
The proposed PhD will combine numerical modeling with hands-on experimental work. The student will develop a detailed model of the experiment, including magnetic fields, radio signal propagation, and detector electronics, validated step by step with real measurements. Once the experiment is running, the PhD candidate will participate in data-taking campaigns and their analysis.
This project provides a unique opportunity to contribute to a state-of-the-art experiment in experimental physics, with direct implications for the global search for dark matter.
Testing the Standard Model in the Higgs-top sector in a new inclusive way with multiple leptons using the ATLAS detector at the LHC
The LHC collides protons at 13.6 TeV, producing a massive dataset to study rare processes and search for new physics. The production of a Higgs boson in association with a single top quark (tH) in the multi-lepton final state (2 same-sign leptons or 3 charged leptons) is particularly promising, but challenging to analyze due to undetected neutrinos and fake leptons. The tH process is especially interesting because its small Standard Model cross section originates from a subtle destructive interference between diagrams including the Higgs coupling to the W boson and the Higgs coupling to the top quark. This makes tH uniquely sensitive: even small deviations from the Standard Model can strongly enhance its production rate. The measurement of the tH cross section is delicate because the ttH and ttW processes have similar topologies and much larger cross sections, requiring a simultaneous extraction to obtain a reliable result and properly account for correlations between signals. ATLAS observed a moderate excess of tH using the Run 2 dataset (2.8 s), making the analysis of Run 3 data including these correlations crucial. The thesis will first exploit AI algorithms based on Transformer architectures to reconstruct event kinematics and extract observables sensitive to the CP nature of the Higgs-top coupling. In a second phase, a global approach will be adopted to analyze simultaneously the ttW, ttZ, ttH, tH, and 4-top processes, searching for anomalous couplings, including those violating CP symmetry, within the framework of the Standard Model Effective Field Theory (SMEFT). This study will provide the first complete measurement of tH in the multi-lepton channel with Run 3 data and will pave the way for a global analysis of rare processes and anomalous couplings at the LHC in this channel.
The combined effects of hypoxia and matrix stiffness on the pathophysiology of pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease characterized by excessive extracellular matrix (ECM) deposition, increased tissue stiffness, and localized hypoxia. These alterations disrupt cell–cell interactions within the alveolo-capillary barrier and drive fibrotic progression. This project aims to investigate, under controlled in vitro conditions, the combined impact of mechanical stiffness and hypoxic stress on the fate and phenotype of pulmonary cell types and their intercellular communication. To achieve this, biomimetic polyacrylamide hydrogels with tunable stiffness and specific ECM protein coatings will be developed to support the co-culture of alveolar epithelial cells, endothelial cells, fibroblasts, and macrophages. Cellular responses will be assessed through proteomics, imaging, and secretome profiling. The goal is to identify key mechano- and chemo-dependent pro-fibrotic factors, providing new insights into IPF pathogenesis and opening avenues for targeted therapeutic strategies and lung tissue regeneration.
Exploring mechanisms of action of vaccine induced protection against infectious diseases in humans
The project aims at unravelling the molecular and cellular mechanisms that contribute to long-term protection induced by vaccines. Early changes (hours and days) occurring at site of injection and distant sites following vaccine injection will be correlated to long lasting (beyond 12 months) induction of neutralizing antibodies and specific T and B cell memory. A particular focus will be made to the relation of immune response with vaccine antigen persistence in the organisms. Multiple omics approaches will be applied to different tissue compartments of animals vaccinated with the yellow fever vaccine (Stamaril) known to induce a remarkable durable response, to then inform the design of new generation of anti-poxvirus vaccines.
Search for di-Higgs production in the multilepton channel with the ATLAS detector using 13.6 TeV data
In the Standard Model (SM), the Higgs field is responsible for the breaking of the electroweak symmetry, thereby giving mass to the W and Z bosons. The discovery of the Higgs boson in 2012 at the LHC provided experimental confirmation of the existence of this field. Despite extensive studies, the self-coupling of the Higgs boson remains unmeasured, yet it is crucial for understanding the shape of the Higgs potential and the stability of the universe’s vacuum. Studying Higgs pair production (di-Higgs) is the only direct way to access this parameter, providing key insights into the electroweak phase transition after the Big Bang. Di-Higgs production is extremely rare (cross-section ~40 fb for proton-proton collisions at a centre-of-mass energy of 13.6 TeV), and among its possible final states, the multilepton channel is promising due to its distinctive kinematics, though complex due to diverse topologies and backgrounds. Recent advances in artificial intelligence, particularly transformer-based architectures respecting physical symmetries, have recently significantly improved event reconstruction in complex Higgs channels such as HH?4b or HH?bbtt. Applying these techniques to the multilepton channel offers strong potential to enhance sensitivity. This PhD project will focus on searching for di-Higgs production in the multilepton final state with the full ATLAS Run 3 dataset at 13.6 TeV, leveraging the group’s ongoing ttH multilepton work to develop advanced AI-based reconstruction and analysis methods. The projet aims to approach SM sensitivity for the Higgs self-coupling.
Higgs boson decay into a Z boson and a photon and time resolution of the CMS electromagnetic calorimeter
The thesis focuses on Higgs boson physics, specifically one of its rare and yet unobserved decay channels: the decay into a Z boson and a photon (Zgamma channel). This decay not only complements our understanding of the Higgs boson but also uniquely involves all currently known neutral bosons (Higgs, Z, photon) and is sensitive to potential processes beyond the Standard Model. The final state of the analysis consists of the two lepton decay products from the Z boson (muons or electrons for this study) and a photon. Background events produced by other Standard Model processes that contain two leptons and a photon (or misidentified particles) form the background of the analysis. With all data gathered during LHC Run 2 (2015-2018) and Run 3 (2021-2026), it is possible to have evidence of this decay, that is to observe it with a statistical significance exceeding three standard deviations.
In addition, the thesis includes an instrumental part focused on optimizing the time resolution of the CMS electromagnetic calorimeter (ECAL). Although designed for precise energy measurements, the ECAL also shows excellent timing resolution for photons and electrons (approximately 150 ps in collisions, 70 ps in test beam conditions). In a final state populated by photons from multiple overlapping events (pileup), the arrival time of a photon helps to verify its compatibility with the Higgs boson decay vertex. This will be crucial during the high-luminosity phase of the LHC (2029 onward), when the number of overlapping events is expected to be about three times greater than today. A new readout electronics for the ECAL is being developed and will be installed in the ECAL and CMS during the duration of the thesis. The new electronics achieves a timing resolution of 30 ps for high-energy photons and electrons. This performance was tested in ideal beam conditions (no magnetic fields, no tracker material in front of ECAL, no pileup). The thesis aims to develop algorithms to maintain this performance within CMS.
The thesis work is a continuation of the ongoing Z? analysis within the CMS group at CEA Saclay and the timing performance analysis of the ECAL, where the Saclay group is a leader. Simple, robust, and efficient analysis tools written in modern C++ and leveraging the ROOT analysis framework allow to understand and contribute to every stage of the analysis, from raw data to published results. The CMS Saclay group has leading responsibilities in CMS since its construction, including deep expertise in Higgs physics, electron and photon reconstruction, detector simulation, and machine learning and artificial intelligence techniques.
Regular trips to CERN are proposed for presenting the results of this work to the CMS collaboration and for participating in laboratory tests planned for the new ECAL electronics, as well as for participating to its installation.