Non-invasively exploring the cerebellum microstructure with magnetic resonance
To better diagnose and monitor brain diseases, we need “non-invasive biopsies” to access the tissue cell-type composition and state without opening the skull. Magnetic resonance imaging (MRI) research efforts attempt to tackle the challenge but often lack cellular specificity because of the ubiquitous nature of water. Diffusion-weighted magnetic resonance imaging (dMRS) measures diffusion of intracellular and partly cell specific molecules in a region of interest, and forms a solid basis for resolving cell-types non-invasively. Among challenges, resolving signal contributions from the different cerebellar neurons could help monitor and understand neurodevelopmental and ataxic disorders. The cerebellum is a brain region representing 10% of the brain volume but containing more than half of the brain neurons, with the very large and complex Purkinje cells and the very small and round granule cells, both having very different functions and metabolism. The PhD project aims to disentangle these cells with complementary strategies: a classical dMRS approach and a quantum dMRS approach confronted to the state-of-the-art microstructure MRI methods.
Role of the JMY protein in human brain development and glioblastoma stem cell radioresistance: from brain organoids to therapeutic screening
The JMY protein is an important regulator of the actin cytoskeleton, involved in cell migration and morphogenesis. Expressed in the developing brain, it is associated with several key processes of neurogenesis, including neurite formation, dendritogenesis, myelination, and neuronal migration. However, its specific role in human brain development remains poorly characterized.
In parallel, our work demonstrates that JMY plays a central role in the pathophysiology of glioblastoma, a highly aggressive brain tumor. Following irradiation, glioblastoma stem cells increase their migratory and invasive capacities through a pathway involving HIF1a and JMY. This activation promotes the formation of actin-rich structures known as tumor microtubes, which are associated with therapeutic resistance.
This project aims to investigate JMY as a common regulator of neurodevelopment and tumor plasticity.
In a first axis, we will analyze the impact of JMY deficiency in human brain organoids derived from iPS cells, in order to assess its effects on proliferation, differentiation, neurogenesis, and cortical organization.
In a second axis, a high-throughput pharmacological screening will be conducted to identify inhibitors capable of blocking radiation-induced migration of glioblastoma tumor stem cells.
The expected results will improve our understanding of JMY’s role in the human brain and support the development of new strategies aimed at limiting glioblastoma recurrence after radiotherapy.
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.
Infertility is a growing problem in all developed countries. The standard methods for the diagnostic of male infertility examine the concentration, motility and morphological anomalies of individual sperm cells. However, 40% of male infertility cases remain unexplained with the standard diagnostic tools.
In this thesis, we will explore the possibility to determine the male infertility causes from the detailed analysis of 3D trajectories and morphology of sperms swimming freely in the environment mimicking the conditions in the female reproductive tract. For this challenging task, we will develop a dedicated microscope based on holography for fast imaging and tracking of individual sperm cells. Along with classical numerical methods, we will use up-to date artificial intelligence algorithms for improving the imaging quality as well as for analysis of multi-dimensional data.
Throughout the project we will closely collaborate with medical research institute (CHU/IAB) specialized in Assisted Reproductive Technologies (ART). We will be examining real patient samples in order to develop a new tool for male infertility diagnosis.
Understanding and modulating resistance to transferrin receptor targeted internal radiotherapy.
This project aims to unravel the mechanisms of resistance to transferrin receptor–targeted internal radiotherapy (RIV-Tf) in lung cancer. RIV-Tf may combine localized cytotoxic effects with a potential modulation of the tumor microenvironment, offering a promising thera(g)nostic strategy. Preliminary data show significant tumor reduction without complete remission, suggesting adaptive resistance mechanisms. The project integrates transcriptomic analyses enabled by a microfluidic platform developed at LICB and various biological techniques (flow cytometry, ELISA, western blot, targeted imaging) to identify molecular and immunological signatures associated with treatment response. These signatures will be validated in vivo to guide rational therapeutic combinations. Conducted jointly by the ImmunoMaps and LICB teams at CEA, this multidisciplinary work will deepen our understanding of the interplay between radiobiology and tumor immunity and help optimize RIV efficacy in oncology.
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.
Advanced methods of blockwise diffusion imaging for studying fetal cerebral development at the mesoscopic scale
The second half of pregnancy is an extremely rich period in terms of brain development, during which key processes such as neurogenesis, neuronal migration, and axonal growth take place; transient structures form and disappear, while brain volume increases more than tenfold. A blockwise ex-vivo imaging technique recently developed in NeuroSpin allows us to take a new look on developing brain tissues, leveraging ultra-high-field MRI at 11.7 teslas to acquire unprecedented whole-brain images at mesoscopic resolution (100 to 200 µm 3D isotropic) . The acquired data is highly multiparametric, including quantitative T1, T2, and T2* mapping, as well as high angular resolution, multi-shell diffusion-weighted imaging (b = 1500, 4500, 8000 s/mm² with 25, 60, and 90 directions respectively) at 200 µm isotropic resolution.
In order to reach such a high level of detail, a small-bore scanner is used (5 cm usable diameter) over extended scanning times (150 hours per field of view). Brains older than about 20 gestational weeks are too large, and are sectioned into blocks whose size is compatible with the scanner. The resulting blockwise images are registered using a dedicated semi-automatic protocol, and fused to reconstruct a set of whole-brain images. While this protocol has allowed us to obtain good-quality images on several fetal brain specimens (3 published, 3 other brains in progress as of the end of 2025), the diffusion imaging data remains to be fully analyzed: indeed, the blockwise nature of the acquisitions poses unique challenges, notably due to the discontinuity at the boundary between blocks, but also to non-linear image deformations and non-linearity of the magnetic field gradients.
The PhD candidate will be hosted in the inDEV team (imaging neurodevelopmental phenotypes) in close collaboration (co-supervision) with the Ginkgo team, which has leading expertise in diffusion imaging methods and has pioneered the blockwise acquisition technique in an adult brain known as Chenonceau. The PhD work lies at the interface between imaging, algorithmics, and developmental neuroscience: it will include developing and benchmarking new methods for processing this blockwise diffusion MRI to obtain high-quality tractography and fit diffusion microstructural models. It will also include an experimental part, where the PhD candidate will take part in the acquisition and reconstruction of new brains, both typical specimens and pathological ones with agenesis of the corpus callosum. Finally, the candidate will explore neuroscientific outcomes of this unprecedented dataset, which has exceptional potential to describe processes such as the development of subcortical pathways and associative white matter fibre tracts, and to become the first atlas of the developing fetal brain with fibre architecture at the mesoscopic scale.
Development of monoclonal antibodies for the diagnostic and the treatement of hypervirulent-Klebsiella pneumoniae
For several years, we have observed the emergence of hypervirulent (hvKp) strains of Klebsiella pneumoniae that have become highly resistant to antibiotics. In a context of dwindling antibiotic options, monoclonal antibodies (Abs) directed against well-conserved capsular antigens of these hvKp strains appear as a promising therapeutic alternative.
This PhD project is structured around three complementary objectives:
1. To describe the circulation of hvKp clones through comparative genomic analysis of strains collected via the French National Reference Center for Antibiotic Resistance and through an international collaboration.
2. To produce and characterize monoclonal Abs directed against the HvKp capsule.
3. To develop a rapid detection tool based on MALDI-TOF profile analysis coupled with machine learning algorithms.
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