Optimising the enzymatic degradation of polylactic acid (PLA) to produce biohydrogen (BioH2) through photofermentation.
This thesis project presents a novel method of producing biohydrogen (BioH2) through the enzymatic breakdown of polylactic acid (PLA), a bioplastic which is challenging to recycle. The aim is to optimise the hydrolysis of PLA into lactic acid, which can be metabolised directly by purple non-sulfur bacteria (PNSB) to produce BioH2 in anoxic conditions. The work will entail selecting high-performance esterases in collaboration with Génoscope CEA, expressing them in soluble form in model hosts such as E. coli, yeasts and PNSB, and optimising reaction conditions such as pH, temperature and concentration to maximise lactic acid production. The second phase will focus on enhancing photofermentation in a photobioreactor (PBR) with advanced control systems (LED, AI and CFD). Funded by the CEA and PUI Grenoble Alpes, this project is part of a circular economy approach, aiming to develop a scalable process for converting PLA waste into renewable energy in line with the challenges of the energy transition.
Numerical and experimental study of cryogenic refrigeration system for HTS-based nuclear fusion reactors
The challenge of climate change and the promise of CO2-free energy production are driving the development of new nuclear fusion reactor concepts that differ significantly from systems such as ITER or JT60-SA [R1]. These new fusion reactors push the technological boundaries by reducing investment and operating costs through the use of high-temperature magnets (HTS) to confine the plasma [R4]. These HTS promise to achieve high-intensity magnetic fields while operating at higher cooling temperatures, thereby reducing the complexity of cryogenic cooling, which is normally achieved by forced circulation of supercritical helium at approximately 4.5 K (see 1.8 K for WEST/Tore Supra) delivered by a dedicated cryogenic plant.
The pulsed operation of tokamaks induces a temporal variation in the thermal load absorbed by the cooling system. This operating scenario has led to the development of several load smoothing techniques to reduce the amplitude of these thermal load variations, thereby reducing the size and power of the cooling system, with beneficial effects on cost and environmental impact. These techniques use liquid helium baths (at approximately 4 K) to absorb and temporarily store some of the thermal energy released by the plasma pulse before transferring it to the cryogenic installation [R5].
The objective of this thesis is to contribute to the development of innovative concepts for the refrigeration of large HTS systems at temperatures between 5 and 20 K. It will include (1) the modeling of cryogenic system and cryodistribution architectures as a function of the heat transfer fluid temperature, and (2) the exploration of innovative load smoothing techniques in collaboration with the multidisciplinary "Fusion Plant" team of the PEPR SUPRAFUSION project. The first part will involve the development and improvement of 0D/1D numerical tools called Simcryogenics, based on Matlab/Simscape [R6], through the implementation of physical models (closure laws) and the selection of appropriate modeling techniques to analyze and compare suitable architectural solutions. The second part will be experimental and will involve conducting load smoothing experiments using an existing cryogenic loop operating between 8 and 15 K.
This activity will be at the forefront of the nuclear fusion revolution currently underway in Europe [R3, R7] and the United States [R4], addressing a wide range of cryogenic engineering fields such as refrigeration technologies, superfluid helium, thermo-hydraulics, materials properties, system and subsystem design, and the design and execution of cryogenic tests. It will thus be useful for the development of new generations of particle accelerators using HTS magnets.
[R1] Cryogenic requirements for the JT-60SA Tokamak https://doi.org/10.1063/1.4706907]
[R2] Analysis of Cryogenic Cooling of Toroidal Field Magnets for Nuclear Fusion Reactorshttps://hdl.handle.net/1721.1/144277
[R3] https://tokamakenergy.com/our-fusion-energy-and-hts-technology/fusion-energy-technology/
[R4] https://tokamakenergy.com/our-fusion-energy-and-hts-technology/hts-business/
[R5] “Forced flow cryogenic cooling in fusion devices: A review” https://doi.org/10.1016/j.heliyon.2021.e06053
[R6] “Simcryogenics: a Library to Simulate and Optimize Cryoplant and Cryodistribution Dynamics”, 10.1088/1757-899X/755/1/012076
[R7] https://renfusion.eu/
[R8] PEPR Suprafusion https://suprafusion.fr/
Structural snapshots of a substrate within the active site of a mitogen-activated protein kinase
Mitogen-activated protein kinases (MAPKs) are key signaling enzymes that regulate cellular stress responses through the phosphorylation of specific protein substrates. Dysregulation of MAPK signaling contributes to numerous diseases, including cancer and neurodegenerative disorders. Although MAPK activation and catalytic mechanisms are well characterized, the structural basis of substrate specificity remains unknown. This project aims to address this gap by capturing atomic-level structural snapshots of substrates bound within the active site of the c-Jun N-terminal kinase 1 (JNK1). To achieve this, we will employ X-ray crystallography together with innovative nuclear magnetic resonance (NMR) methods that integrate selective methyl isotope labeling and photoactivatable catalysis. By elucidating the structural details of how substrates are recognized by the active site of JNK1, our work will open new avenues for the development of substrate-competitive inhibitors of MAPKs with enhanced selectivity and therapeutic potential.
V-SYNTHES-guided discovery of BET bromodomain inhibitors : a novel antifungal strategy against Candida auris
New antifungal strategies are urgently needed to combat Candida auris, an emerging multidrug-resistant fungal "superbug" responsible for severe hospital outbreaks and high-mortality infections. Our previous proof-of-concept studies in Candida albicans and Candida glabrata established that fungal BET bromodomains – chromatin-binding modules that recognize acetylated histones – represent promising new antifungal targets. We have developed an advanced set of molecular and cellular tools to accelerate antifungal BET inhibitor discovery, including FRET-based assays for compound screening, humanized Candida strains for on-target validation, and NanoBiT assays to monitor BET bromodomain inhibition directly in fungal cells.
This PhD project represents the translational next phase of our research program. It will exploit the AI-guided V-SYNTHES drug discovery approach – a cutting-edge virtual screening and design framework – to develop highly potent BET inhibitors targeting C. auris. Inhibitors will be profiled in biophysical, biochemical and cellular assays, structurally characterized in complex with their bromodomain targets, and validated for on-target activity in C. auris and antifungal efficacy in animal infection models. They will also be used to explore the emergence of resistance to BET inhibition. This project combines an original antifungal strategy with an innovative methodological approach, offering a unique framework for training in interdisciplinary and translational research.
Triplet superconductors: from weak to strong spin-orbit coupling
Since the 1980s, several unconventional superconductors have been discovered, some of which exhibit triplet pairing (total spin S=1) that may lead to interesting topological properties. Unlike singlet superconductors, their order parameter is a vector depending on the spin components (S_z=-1,0,1) and is strongly influenced by the crystal symmetry and the spin–orbit coupling (SO).
The thesis aims to study the transition between weak and strong spin–orbit coupling in a triplet superconductor, using a minimal multiband model inspired by the material CdRh2As3, where a field-induced triplet phase was recently observed. This research will enable the calculation of the dynamic spin susceptibility and the identification of possible collective spin resonances, similar to those seen in superfluid He3.
The project will mainly rely on analytical field-theoretical methods applied to condensed matter. It is intended for candidates with a solid background in quantum mechanics, statistical physics, and solid-state physics.
Growth and Characterization of AlScN: A New Promising Material for Piezoelectric and Ferroelectric Devices
III-nitride semiconductors — GaN, AlN, and InN — have revolutionized the lighting market and are rapidly entering the power electronics sector. Currently, new nitride compounds are being explored in the search for novel functionalities. In this context, aluminum scandium nitride (AlScN) has emerged as a particularly promising new member of the nitride family. Incorporating scandium into AlN leads to:
* Enhanced Piezoelectric Constants: Making AlScN highly attractive for the fabrication of piezoelectric generators and high-frequency SAW/BAW filters.
* Increased Spontaneous Polarization: The enhanced polarization can be exploited in designing high-electron-mobility transistors (HEMTs) with very high channel charge densities.
* Ferroelectricity: The recently discovered (2019) emergence of ferroelectric properties opens up possibilities for developing new non-volatile memory devices.
Over the past five years, AlScN has become a major focus of research, presenting numerous open questions and exciting opportunities to explore.
This PhD thesis will focus on the study of the growth and properties of AlScN and GaScN synthesized by molecular beam epitaxy (MBE). The student will receive training in the use of an MBE system for the synthesis of III-nitride semiconductors and in the structural characterization of materials using atomic force microscopy (AFM) and X-ray diffraction (XRD). The variation of the polarization properties of the materials will be investigated by analyzing the photoluminescence of quantum well structures. Finally, the student will be trained in the use of simulation software to model the electronic structure of the samples, aiding in the interpretation of the optical results.
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
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.
Magneto-mechanical stimulation for the selective destruction of pancreatic cancer cells while sparing healthy cells
A novel approach for selectively destroying cancer cells is being developed through a collaboration between the BIOMICS biology laboratory and the SPINTEC magnetism laboratory, both part of the IRIG Institute. This method employs magnetic particles dispersed among cancer cells, which are set into low-frequency vibration (1–20 Hz) by an applied rotating magnetic field. The resulting mechanical stress induces controlled cell death (apoptosis) in the targeted cells.
The effect has been demonstrated in vitro across various cancer cell types—including glioma, pancreatic, and renal cells—in 2D cultures, as well as in 3D pancreatic cancer spheroids (tumoroids) and healthy pancreatic organoids. These 3D models, which more closely mimic the structure and organization of real biological tissues, facilitate the transition to in vivo studies and reduce reliance on animal models. Preliminary findings indicate that pancreatic cancer cells exhibit a higher affinity for magnetic particles and are more sensitive to mechanical stress than healthy cells, enabling selective destruction of cancer cells while sparing healthy tissue.
The next phase will involve confirming this specificity in mixed spheroids (containing both cancerous and healthy cells), statistically quantifying the results, and elucidating the mechanobiological mechanisms underlying cell death. These promising findings pave the way for an innovative biomedical approach to cancer treatment.
Endothelial-fibroblast interactions in diabetic foot ulcer: deciphering the intercellular communication responsible for the chronic wound persistence
Diabetic foot ulcer (DFU), a severe complication of diabetes affecting approximately 18.6 million people worldwide each year, is associated with high rates of amputation and mortality. Like other chronic wounds, DFUs exhibit impaired healing due to a dysregulated cascade of cellular signalling and behavioural events that normally ensure rapid closure of the skin barrier. Among the key cellular players, fibroblasts and endothelial cells are central to the proliferative and remodelling phases of wound repair – processes that are notably dysfunctional in chronic wounds. Although endothelial-fibroblast crosstalk is recognized as an essential driver of normal skin healing, the specific mechanisms governing their interaction in DFU is poorly understood.
The main objective of this PhD project is to decipher the intercellular communication between endothelial cells and fibroblasts that underlies the chronicity of DFU. Particular attention will be devoted to extracellular vesicle-associated microRNAs (miRNAs), which are pivotal regulators of intercellular communication through modulation of gene expression in recipient cells. By characterizing the repertoire of pro- and anti-healing miRNAs exchanged between endothelial cells and fibroblasts, this project seeks to uncover novel molecular targets and therapeutic strategies to promote wound repair in diabetic foot ulcers.