Study of the thermomechanical properties of solid hydrogen flows
IRIG's Department of Low Temperature Systems (DSBT) is developing several research themes around cryogenic solid hydrogen and its isotopes. The applications of this research range from the production of renewable micrometre-sized solid hydrogen targets for the generation of high-energy protons for laser-plasma acceleration, to the formation and injection of millimetre- or centimetre-sized hydrogen ice cubes for the supply and control of plasma in fusion reactors using magnetic or inertial confinement. A cross-cutting issue in these applications is the need for a detailed understanding of the mechanical properties of solid hydrogen, in order to gain a better understanding of the physics of extrusion and target production, as well as the formation and acceleration of icicles for injection into fusion plasmas.
The subject of this thesis focuses on the study of solid hydrogen extrusion under pressure. Using this technology, the DSBT has been developing several cryostats for over 10 years, enabling the production of ribbons of solid hydrogen, ranging in size from a few millimetres to a few tens of micrometres, extruded at speeds of a few millimetres per second.
The main objective of the research is to gain a better understanding of extrusion mechanisms to enable the development of numerical predictive tools for extrusion system design. This experimental thesis will be based on cryogenic rheometry using a capillary rheometer and/or a duvet experiment developed during a previous thesis. This study will be carried out in collaboration with the Laboratoire de Rhéologie et Procédés at Grenoble Alpes University.
INVESTIGATION OF CONFORMATIONAL HETEROGENEITY AND DYNAMICS IN FLUORESCENCE ACTIVATING AND ABSORPTION-SHIFTING TAGS (FAST)
Fluorescent proteins, particularly Reversibly Switchable Fluorescent Proteins (RSFPs), have revolutionized advanced fluorescence imaging, paving the way for applications such as super-resolution microscopy. Among emerging alternatives, fluorogen-based reporters, such as the FAST (Fluorescence Activating and Absorption Shifting Tag) system, stand out dur to their enhanced photostability and versatility. FAST operates via non-covalent binding of a small engineered protein to an organic fluorogen, which induces fluorescence and allowing real-time monitoring without chromophore maturation. However, challenges remain in optimizing these systems due to limited mechanistic understanding of fluorogen-protein interactions, binding dynamics, and photophysical behavior under illumination. This PhD project aims to characterize the binding modes of FAST systems at atomic resolution using multidimensional NMR spectroscopy, X-ray crystallography, and UV-visible spectroscopy. Recent findings suggest that fluorogens can adopt multiple binding modes, and that slight chemical modifications impact binding kinetics and fluorescence brightness. By integrating laser-based illumination in NMR investigations, we will further probe how light absorption affects fluorogen conformation and dynamics. The insights gained from this study will enable the rational design of optimized FAST variants, enhancing their performance for specific microscopy applications and advancing the field of fluorescence imaging.
Molecular dynamics and disorder in the viral replication machinery of SARS CoV 2
The nucleocapsid protein (N) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for genome replication, encapsidating the viral genome and regulating gene transcription. The protein is highly disordered, comprising two disordered termini and a central disordered domain that are essential to its function. The central domain contains a number of important mutations that are responsible for enhanced viral fitness, and comprises a region that is hyperphosphorylated during the viral cycle. NMR spectroscopy is the tool of choice for studying the conformational behaviour of intrinsically disordered proteins, an abundant class of proteins that are functional in their disordered form. They represent 40% of the proteome and are too dynamic to be studied by crystallography or electron microscopy. The host lab has developed a large number of unique NMR-based tools to help understand the function of this class of proteins at atomic resolution. We will use NMR, paramagnetic NMR, small angle scattering, single molecule FRET and electron microscopy, in combination with molecular dynamics simulation, to describe the interactions of N with viral partner proteins and viral RNA to describe the process of encapsidation of the viral genome by the nucleocapsid protein, as well as the impact of mutations present in variants of concern. The results will be correlated with light and electron microscopy, carried out in collaboration.
HLA-G: a new target for the addressing of anti-tumor therapies
The main objective of this project is to demonstrate that the HLA-G molecule can be used to target treatments against a variety of tumors, particularly those lacking specific tumor antigens (TSA).
Project Rationale: HLA-G has two key characteristics that make it attractive for antitumor therapy:
Immunosuppressive function: HLA-G acts as an immune checkpoint, blocking cytotoxic immune cells that are anti-tumor, thereby allowing tumor cells to evade immune surveillance.
Selective expression: HLA-G is primarily a fetal molecule, with virtually no expression in adults. However, it is commonly re-expressed in many solid tumors.
The restricted expression of HLA-G in pathological tissues, mainly tumor cells, makes it an appealing target for therapeutic targeting. This characteristic will be exploited in the project. Indeed, a molecule that is specifically expressed by a tumor is an ideal TSA, enabling targeted treatment with minimal side effects on healthy cells. Unfortunately, tumor-specific antigens are rare, costly to develop, and, for most tumors, none exist to date.
HLA-G, expressed in the majority of tumor types—both common and rare—represents an excellent candidate for a multi-tumor TSA.
Project Methodology
The project will use microfluidic chips and 3D tumor avatars (tumor spheroids derived from patients with renal cancer) already established in the laboratory to evaluate the efficacy of BiTEs (Bi-Specific T-cell Engagers). One side of the BiTEs will target HLA-G as the addressing molecule, and the other side will target tumor-infiltrating cytotoxic cell antigens (T lymphocytes and NK cells).
Resources and Expertise
The project will build on the laboratory’s expertise in:
The HLA-G molecule and its functions in immunology and immuno-oncology, a subject the laboratory has studied for over 20 years.
The immune environment of renal tumors, particularly intratumoral cytotoxic cells.
Clinical expertise in immuno-urology-oncology from clinicians at St. Louis Hospital, Paris.
The project will employ advanced technologies, including spectral flow cytometry and 3D tumor avatars in microfluidic chips.
Conclusion
By using innovative technologies and relying on strong expertise, the project aims to develop new therapeutic strategies applicable to a broad range of cancers expressing HLA-G.
Chiral Superconductors and Thermal Transport
In this PhD project, we intend to probe two well-known unconventional superconductors with thermal transport, through an original approach combining macroscopic and microscopic probes. These superconductors are UPt3 and UTe2, chosen because they address two issues currently under hot debate in the international community, that could strongly benefit from this new approach. UPt3 addresses the question of topological superconductivity, while UTe2 requires a clear identification of its spin-triplet superconducting order parameter.
Topological superconductivity is an active subject on the theoretical side and because of its potential interest in the field of quantum engineering. However, unambiguous experimental results are scarce, and we intend to focus here on UPt3, the first ever superconductor demonstrating the existence of transitions between superconducting phases, together with convincing evidences for chiral superconductivity. The goal is to probe predictions on the existence of an anomalous (zero field) thermal Hall effect, which would arise from the chiral edge currents.
A new approach is proposed, combining a newly designed set-up for the macroscopic measurement of thermal conductivity and thermal Hall effect, together with a microscopic probe realizing Scanning Thermal Spectroscopy. This will be realized thanks to a collaboration between two labratories in Grenoble: a team Pheliqs, mastering high quality crystal growth of these systems together with low temperature thermal transport measurements, and two teams in Néel, experts in Scanning SQUID microscopy and microscopic thermal measurements down to sub-Kelvin temperatures.
With this project, the PhD student will acquire very broad skills, ranging from sample preparation, low temperature instrumentation, and major actual issues in the field of quantum materials.
Trans-splicing gene therapy for Stargardt disease: construction of molecular and cellular tools to target ABCA4 gene mutations
This project aims to develop an innovative therapeutic approach for Stargardt disease, a macular degeneration caused by mutations in the ABCA4 gene. The strategy is based on SMaRT (Spliceosome-Mediated RNA Trans-splicing) technology, which enables mutation correction at the transcriptome level by replacing mutated exons of endogenous mRNA by trans-splicing with an exogenous RNA (PTM). Since the PTM contains only a part of the mRNA to be corrected, this approach can overcome the obstacle of the large size of the ABCA4 cDNA, which exceeds the carrying capacity of AAV vectors. The project will consist of several phases using molecular and cell biology techniques: construction of viral vectors for the expression of PTMs, production of cell lines to test the efficacy of binding domains (BD) to induce trans-splicing, and screening of BDs to optimize PTMs. Selected PTMs will then be tested in retinal organoids and animal models to demonstrate their therapeutic potential for the treatment of this genetic disease. As AAV is currently the most effective vector for retinal transduction, this project could open new therapeutic perspectives for Stargardt disease.
DEFENSOMES, COUNTER-DEFENSOMES, AND THE REMODELING OF MICROBIAL COMMUNITIES
Horizontal gene transfer (HGT) enables bacteria to swiftly adapt to new ecological niches and challenges. This process is primarily facilitated by mobile genetic elements (MGEs), such as bacteriophages (phages), plasmids, and transposable elements, which are prevalent in most genomes, often in multiple copies. The potential for conflicts arising from the interactions between MGEs and bacteria has driven the evolution of sophisticated defense mechanisms to filter, tame, or inactivate these elements. Well studied examples of anti-MGE immunity include restriction-modification (R-M), abortive infection, and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems. Altogether, they revolutionized the field of genome engineering as precise cleavage / stabilization / editing tools, and further propelled the quest for additional defense mechanisms as well as MGE counter-defense strategies capable of curbing their action. The last decade has witnessed the identification and, in some cases, the mechanistic characterization of an extensive arsenal of previously unknown anti-MGE defense systems. These systems can be deployed at various stages of the MGE infection process, either by degrading invading nucleic acids, inhibiting their replication, or inducing dormancy or death of infected cells to stop the mobile element’s spread through the microbial population. With the growing number of anti-MGE families identified, so has the discovery of MGE-encoded counter-defense systems. Such counter-defensome deploys multiple mechanisms to inactivate host immune systems (beyond bacteriophage gene mutations), that include direct binding to immune proteins, post-translational modification of immune proteins, targeting of secondary messengers, and counteracting metabolite-depleting defense systems.
Many of the defense and counter-defense systems known to date have been uncovered through bioinformatic exploration of reference genome databases (e.g., NCBI RefSeq). Yet, the latter overrepresent organisms that can largely be cultivated in laboratory, and therefore provide a limited snapshot of the uncharted fraction of environmental microbial diversity that remains uncultured. To characterize this hidden diversity, we recently performed a large-scale screening of high-quality bacterial population genomes reconstructed from environmental metagenomes, highlighting the diversity of defensomes and the potential for functional cooperation and generation of novel functions between different defensive modules [1]. Findings stemming from this study raised further questions related to the nature of conflicts and alliances between defense system families, breadth of counter-defense strategies in the environmental phageome, as well as the tantalizing prospect of prioritizing core-defense genes for the development of antimicrobials capable of targeting an entire bacterial species. We propose to address such questions in the current proposal as follows:
1) The analysis of defense system co-occurrence / co-localization and synergistic immunity across bacterial species and biomes;
2) A first-of-its kind large-scale mapping of the counter-defensome of phageomes across multiple environments;
3) Analysis of the core layers of the defensome across bacterial species, with additional proof of concept that such genes (many of them now known to be essential), can be used as targets to develop antimicrobials aiming at eliminating an entire bacterial species.
Radiological large-scale accident dosimetry: use of EPR spectroscopy for population triage by measurements of smartphone screens
In the event of a large-scale radiological emergency involving sources of external irradiation, methods are needed to identify which members of the population have been exposed and require priority care. To date, there are no operational methods for such sorting. Smartphone touch screen lenses retain traces of ionizing radiation through the formation of so-called “radiation-induced” defects.Measuring and quantifying these punctual defects, in particular by electron paramagnetic resonance (EPR) spectroscopy, makes itpossible to estimate the dose deposited in the glass, and thus the exposure associated with irradiation. The thesis work proposed herefocuses in particular on the alkali-aluminosilicate glasses used in cell phone touch screens, which are currently the best candidates fordeveloping new measurement capabilities in the context of accidents involving large numbers of victims.
We will focus in particular on identifying point defects as a function of the glass model used in smartphones by simulating EPR spectra in order to optimize the proposed dosimetry method.
Point Spread Function Modelling for Space Telescopes with a Differentiable Optical Model
Context
Weak gravitational lensing [1] is a powerful probe of the Large Scale Structure of our Universe. Cosmologists use weak lensing to study the nature of dark matter and its spatial distribution. Weak lensing missions require highly accurate shape measurements of galaxy images. The instrumental response of the telescope, called the point spread function (PSF), produces a deformation of the observed images. This deformation can be mistaken for the effects of weak lensing in the galaxy images, thus being one of the primary sources of systematic error when doing weak lensing science. Therefore, estimating a reliable and accurate PSF model is crucial for the success of any weak lensing mission [2]. The PSF field can be interpreted as a convolutional kernel that affects each of our observations of interest, which varies spatially, spectrally, and temporally. The PSF model needs to be able to cope with each of these variations. We use specific stars considered point sources in the field of view to constrain our PSF model. These stars, which are unresolved objects, provide us with degraded samples of the PSF field. The observations go through different degradations depending on the properties of the telescope. These degradations include undersampling, integration over the instrument passband, and additive noise. We finally build the PSF model using these degraded observations and then use the model to infer the PSF at the position of galaxies. This procedure constitutes the ill-posed inverse problem of PSF modelling. See [3] for a recent review on PSF modelling.
The recently launched Euclid survey represents one of the most complex challenges for PSF modelling. Because of the very broad passband of Euclid’s visible imager (VIS) ranging from 550nm to 900nm, PSF models need to capture not only the PSF field spatial variations but also its chromatic variations. Each star observation is integrated with the object’s spectral energy distribution (SED) over the whole VIS passband. As the observations are undersampled, a super-resolution step is also required. A recent model coined WaveDiff [4] was proposed to tackle the PSF modelling problem for Euclid and is based on a differentiable optical model. WaveDiff achieved state-of-the-art performance and is currently being tested with recent observations from the Euclid survey.
The James Webb Space Telescope (JWST) was recently launched and is producing outstanding observations. The COSMOS-Web collaboration [5] is a wide-field JWST treasury program that maps a contiguous 0.6 deg2 field. The COSMOS-Web observations are available and provide a unique opportunity to test and develop a precise PSF model for JWST. In this context, several science cases, on top of weak gravitational lensing studies, can vastly profit from a precise PSF model. For example, strong gravitational lensing [6], where the PSF plays a crucial role in reconstruction, and exoplanet imaging [7], where the PSF speckles can mimic the appearance of exoplanets, therefore subtracting an accurate and precise PSF model is essential to improve the imaging and detection of exoplanets.
PhD project
The candidate will aim to develop more accurate and performant PSF models for space-based telescopes exploiting a differentiable optical framework and focus the effort on Euclid and JWST.
The WaveDiff model is based on the wavefront space and does not consider pixel-based or detector-level effects. These pixel errors cannot be modelled accurately in the wavefront as they naturally arise directly on the detectors and are unrelated to the telescope’s optic aberrations. Therefore, as a first direction, we will extend the PSF modelling approach, considering the detector-level effect by combining a parametric and data-driven (learned) approach. We will exploit the automatic differentiation capabilities of machine learning frameworks (e.g. TensorFlow, Pytorch, JAX) of the WaveDiff PSF model to accomplish the objective.
As a second direction, we will consider the joint estimation of the PSF field and the stellar Spectral Energy Densities (SEDs) by exploiting repeated exposures or dithers. The goal is to improve and calibrate the original SED estimation by exploiting the PSF modelling information. We will rely on our PSF model, and repeated observations of the same object will change the star image (as it is imaged on different focal plane positions) but will share the same SEDs.
Another direction will be to extend WaveDiff for more general astronomical observatories like JWST with smaller fields of view. We will need to constrain the PSF model with observations from several bands to build a unique PSF model constrained by more information. The objective is to develop the next PSF model for JWST that is available for widespread use, which we will validate with the available real data from the COSMOS-Web JWST program.
The following direction will be to extend the performance of WaveDiff by including a continuous field in the form of an implicit neural representations [8], or neural fields (NeRF) [9], to address the spatial variations of the PSF in the wavefront space with a more powerful and flexible model.
Finally, throughout the PhD, the candidate will collaborate on Euclid’s data-driven PSF modelling effort, which consists of applying WaveDiff to real Euclid data, and the COSMOS-Web collaboration to exploit JWST observations.
References
[1] R. Mandelbaum. “Weak Lensing for Precision Cosmology”. In: Annual Review of Astronomy and Astro- physics 56 (2018), pp. 393–433. doi: 10.1146/annurev-astro-081817-051928. arXiv: 1710.03235.
[2] T. I. Liaudat et al. “Multi-CCD modelling of the point spread function”. In: A&A 646 (2021), A27. doi:10.1051/0004-6361/202039584.
[3] T. I. Liaudat, J.-L. Starck, and M. Kilbinger. “Point spread function modelling for astronomical telescopes: a review focused on weak gravitational lensing studies”. In: Frontiers in Astronomy and Space Sciences 10 (2023). doi: 10.3389/fspas.2023.1158213.
[4] T. I. Liaudat, J.-L. Starck, M. Kilbinger, and P.-A. Frugier. “Rethinking data-driven point spread function modeling with a differentiable optical model”. In: Inverse Problems 39.3 (Feb. 2023), p. 035008. doi:10.1088/1361-6420/acb664.
[5] C. M. Casey et al. “COSMOS-Web: An Overview of the JWST Cosmic Origins Survey”. In: The Astrophysical Journal 954.1 (Aug. 2023), p. 31. doi: 10.3847/1538-4357/acc2bc.
[6] A. Acebron et al. “The Next Step in Galaxy Cluster Strong Lensing: Modeling the Surface Brightness of Multiply Imaged Sources”. In: ApJ 976.1, 110 (Nov. 2024), p. 110. doi: 10.3847/1538-4357/ad8343. arXiv: 2410.01883 [astro-ph.GA].
[7] B. Y. Feng et al. “Exoplanet Imaging via Differentiable Rendering”. In: IEEE Transactions on Computational Imaging 11 (2025), pp. 36–51. doi: 10.1109/TCI.2025.3525971.
[8] Y. Xie et al. “Neural Fields in Visual Computing and Beyond”. In: arXiv e-prints, arXiv:2111.11426 (Nov.2021), arXiv:2111.11426. doi: 10.48550/arXiv.2111.11426. arXiv: 2111.11426 [cs.CV].
[9] B. Mildenhall et al. “NeRF: Representing Scenes as Neural Radiance Fields for View Synthesis”. In: arXiv e-prints, arXiv:2003.08934 (Mar. 2020), arXiv:2003.08934. doi: 10.48550/arXiv.2003.08934. arXiv:2003.08934 [cs.CV].
Analysis and experimental study of capillary structures to mitigate the influence of magnetogravitational forces on liquid helium cooling for future HTS superconducting magnets
As physics requires increasingly higher magnetic fields, CEA is called upon to develop and produce superconducting magnets capable of generating magnetic field of more than 30 T. The windings of these electromagnets are made from superconducting materials whose electrical resistance is extremely low at cryogenic temperatures (a few Kelvins). This enables them to carry high currents (>10 kA) while dissipating a minimum of heat by Joule effect. Cooling at these low temperatures is achieved using liquid helium. But helium is diamagnetic. Magnetic fields will therefore induce volumetric forces that add to or oppose gravity within the helium. These magneto-gravity forces disrupt the convective phenomena required to cool the superconducting magnet. This can lead to a rise in their temperature and a loss of their superconducting state, which is essential for their proper operation. In order to circumvent this phenomenon, a new cooling system never used in cryomagnetism will be studied. This cooling system will be developed using heat pipes whose operation is based on capillary forces that are theoretically independent of the magneto-gravity forces induced by strong magnetic fields. These capillary structures can take several forms (microchannels, foam, mesh, etc.). In the framework of the thesis these different structures will be studied theoretically and then experimentally, both with and without magnetic forces, in order to determine the most suitable structures for the future superconducting magnets.