Development of a Modular Enzymatic Platform for the In Silico Design and Synthesis of Novel Therapeutic Peptides via Protein Splicing
The rise of antimicrobial resistance (AMR) has developed into a slow-moving epidemic, fueled by the overuse and misuse of antibiotics, coupled with a stagnation in the development of new antimicrobial agents over the past four decades. Addressing this crisis requires not only more judicious use of existing antibiotics but also the development of innovative drugs capable of overcoming resistant pathogens. In this context, the abundant genomic data generated in the omics era has facilitated the resurgence of natural products as a vital source of novel compounds. Among these, natural peptides—with their unique and diverse chemical properties—have garnered particular interest as potential antibiotics, anticancer agents, and inhibitors targeting specific pathological processes.
The aim of this PhD project is to develop a novel, modular enzymatic tool that enables the in silico design and synthesis of peptides with unprecedented chemical diversity. Central to this approach is the exploitation of a unique chemical reaction: protein splicing. This innovative reaction allows precise removal or editing of specific peptidic sequences, thereby providing a powerful platform to generate hybrid peptides with tailored functionalities, including potential therapeutic agents.
This project will integrate structural and functional studies, computational peptide design and enzyme engineering, aiming to expand the chemical and functional diversity of peptide-based molecules. The successful candidate will work in a state-of-the-art research setting, equipped with cutting-edge facilities and collaborative opportunities, fostering innovative approaches and impactful contributions to the field.
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.
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.
Regulation of gene expression by acetylation and lactylation of histone proteins
In eukaryotic cells, DNA wraps around histone proteins to form chromatin. Dynamic modification of histones by various chemical structures allows for fine regulation of gene expression. Alterations in these complex regulatory mechanisms are responsible for many diseases. Acetylation of histone lysines is known to induce gene expression. Other structures can be added to histones, whose effects on transcription remain largely unclear. Most of them, such as lactylation discovered in 2019, depend on cellular metabolism. We are studying this new modification in murine spermatogenesis: this process of cell differentiation is an ideal model for studying transcription regulation, due to dramatic changes in chromatin composition and gene expression patterns. We have established the distribution of acetylated and lactylated marks on three lysines of histone H3 across the genome. The aim of this thesis is to contribute to deciphering the “histone language,” first by studying the role of lactylations on the transcriptional program. Next, the prediction of chromatin states will be refined by integrating our new data with numerous available epigenomic data within neural network models.
Theoretical studies of orbital current and their conversion mechnism for leveraging spin-orbit torques based devices performances
The proposed PhD thesis aims at understanding and identifying the key parameters governing the conversion of orbital moments into spin currents, with the goal of enhancing the write efficiency of spin-orbit torque magnetic random-access memory (SOT-MRAM) devices. The work will employ a multiscale modeling approach comprising ab initio, tight-binding and atomistic calculations of the Orbital Hall Effect (OHE) and Orbital Rashba-Edelstein Effect (OREE). These phenomena exhibit larger magnitudes and diffusion lengths compared to their spin counterparts, Spin Hall Effect (SHE) and Rashba-Edelstein Effect (REE). Furthermore, they are present in a broader range of materials, including low-resistivity light metals. This opens very interesting opportunities for more efficient and conductive materials, potentially lifting the barriers limiting the technological deployment of SOT-MRAM.
This thesis will play a key role in a close collaboration between SPINTEC and LETI laboratories at CEA. The PhD student will conduct ab initio calculations at SPINTEC to unveil fundamental material characteristics to exploit the described orbitronic phenomena, and will construct multi-orbital Hamiltonians at LETI to calculate orbital and spin transport, in strong interaction/synergy with experimentalists working on SOT-MRAM development. The PhD will be co-supervised by M. Chshiev, K. Garello at Spintec and J. Li at LETI. This PhD project will be at the heart of collaborations with leading theoretical and experimental groups at national and international level.
Highly motivated candidates with a strong background in solid-state physics, condensed matter theory, and numerical simulations are encouraged to apply. The selected candidate will perform calculations using Spintec’s computational cluster, leveraging first-principles DFT-based packages and other simulation tools. Results will be rigorously analyzed, with opportunities for publication in international peer-reviewed journals.
Deep UV-LEDs based on digital alloys (GaN)n/(AlN)m
Context :
Group-III nitride semiconductors (GaN, AlN, InN) are renowned for their outstanding light emission properties. For more than two decades, they have powered the blue and white LEDs used worldwide, thanks to highly efficient InGaN quantum wells (external quantum efficiency > 80%). In contrast, UV LEDs based on AlGaN quantum wells are still very inefficient (< 10%) and only recently became commercially available. Overcoming this limitation is a key challenge in optoelectronics: achieving efficient deep-UV emission (220–280 nm) would enable high-performance bactericidal applications such as water purification, surface sterilization, and virus inactivation.
Recently, two breakthrough concepts are promising to explore for UV-LEDs:
1. Deep-UV emission from GaN monolayers in AlN: Grow a few atomic monolayers (MLs) of GaN embedded in an AlN matrix. This extreme quantum confinement leads to deep-UV emission down to 220 nm. High emission efficiency is expected due to strong exciton binding, stable even at room temperature
2. Enhanced doping using graded digital GaN/AlN alloys: Use graded digital alloys (GaN)?/(AlN)? where n and m are the number of atomic layers. This architecture enables efficient n- and especially p-type doping, which is a major bottleneck in AlGaN. GaN is much easier to dope than AlN, making this approach very promising for device fabrication.
Scientific Targets :
The aim is to master monolayer growth using MOVPE (metal-organic vapor phase epitaxy), the most industrially relevant technique :
- M2 project: develop the growth of GaN monolayers on AlN substrates, study their deep-UV emission properties, and optimize growth conditions for self-limited single-layer deposition.
- PhD continuation: design and fabricate doped digital GaN/AlN alloys to build the first efficient deep-UV LEDs based on this architecture.
Lab background and collaboration:
The group has long-standing expertise in visible and UV light emission from nitride nanowires. We have already demonstrated 280 nm emission from (GaN)?/(AlGaN)? digital alloys, proving the viability of this approach. The project will be highly experimental (epitaxy, advanced structural and optical characterization) and conducted in close collaboration with Institut Néel for cathodoluminescence analysis and device processing.
Why join this project ?
Gain expertise in epitaxy, semiconductor physics, and optoelectronics. Work in a dynamic, collaborative environment with strong ties to industry. Contribute to the development of the next generation of deep-UV LEDs.
Real-space fitting of flexible molecular structures in high-speed AFM topographic movies
Structural biology seeks to understand the function of macromolecules by determining the precise position of their atoms. Its traditional methods (X-ray crystallography, NMR, electron microscopy), although effective, offer a static view of macromolecules, limiting the study of their dynamics. A new paradigm is emerging: integrative structural biology, combining several techniques to capture, among other things, molecular dynamics. However, despite improvements in femtosecond serial crystallography, molecular dynamics simulations, and cryo-electron tomography, current methods struggle to reach the functional time scale (milliseconds to seconds).
The advent of new scanning probe microscopy, and in particular the recent development of high-speed atomic force microscopy (HS-AFM), allows molecular movements to be observed on the millisecond scale, but lacks the atomic resolution to revolutionize structural biology. The objective of the proposed topic is to further exploit the use of HS-AFM by modeling detailed atomic structures at the heart of the images obtained. The tasks will be both biophysical and computational, involving the improvement of the existing AFM-Assembly tool, which allows direct spatial adjustment of the atomic coordinates of the target molecule under AFM topography. The aim is to apply this protocol to a new type of big data, namely topographical movies obtained by high-speed AFM.
The thesis will be conducted at the Institute of Structural Biology in Grenoble, within the Methods and Electron Microscopy (MEM) group of the Grenoble Interdisciplinary Research Institute (IRIG). It will be carried out in collaboration with the DyNaMo laboratory in Marseille, which specializes in high-speed AFM data acquisition, as part of a joint ANR funding application.
The scientific interest of the project is major for modern integrative structural biology. The great scientific challenge of the coming years in structural biology is the study and analysis of molecular dynamics, in order to move beyond the current paradigm (instantaneous photography) and participate in the emergence of a new paradigm (real-time movie).
A new altermagnetic material with remarkable properties for spintronics
Altermagnets represent a new class of magnetic materials that uniquely combine the advantages of ferromagnets (spin polarization of electric currents) and antiferromagnets (robustness against magnetic fields and ultrafast spin dynamics). As part of an international collaboration, we have experimentally discovered one of the very first and still rare altermagnets, Mn5Si3, thereby opening the way for new fundamental and applied research. Until now, Mn5Si3 has mainly been synthesized by molecular beam epitaxy, a high-precision technique but one that presents limitations for broader studies. Our goal is to develop the growth of Mn5Si3 using high-temperature sputtering, a more versatile and industry-compatible method, in order to explore and demonstrate its exceptional spin properties.
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.
Development of photo-printed interferometric biosensors on multi-core optical fibers for molecular diagnostics
Optical fibers are minimally invasive devices commonly used in medicine for in vivo tissue imaging by endoscopy. However, at present, they only provide images and no molecular information about the tissues observed. The proposed thesis is part of a project aimed at giving optical fibers the ability to perform molecular recognition in order to develop innovative biosensors capable of performing real-time, remote, in situ, and multiplexed molecular analysis. Such a tool could lead to significant advances in the medical field, particularly in the study of brain pathologies, where knowledge of the tumor environment, which is difficult to access using conventional biopsies, is essential.
The proposed approach is based on 2-photon polymerization printing of interferometric structures at the end of each core of a multifiber assembly. The detection principle is based on the interference occurring in these structures and their modification by the adsorption of biological molecules. Each fiber in the assembly will act as an individual sensor, and measuring the intensity of the light reflected at the functionalized end will provide information about the biological interactions occurring on that surface. By modeling the interference phenomenon, we determined parameters to optimize the shape and sensitivity of interferometric structures (PTC InSiBio 2024-2025). These results enabled the printing and characterization of the sensitivity of interferometric structures on single-core fibers. The objectives of the thesis are to continue this optical characterization on new samples and to develop original photochemical functionalization methods in order to graft several biological probes onto the surface of the fiber assemblies. This multi-functionalization will enable multiplexed detection, which is essential for future medical applications. Depending on the progress of the thesis, the biosensors will be validated through the detection of biological targets in increasingly complex environments, up to and including a brain tissue model.