Towards a better understanding of membrane proteins through AI
Despite the remarkable advances in artificial intelligence (AI), particularly with tools like AlphaFold, the prediction of membrane protein structures remains a major challenge in structural biology. These proteins, which represent 30% of the proteome and 60% of therapeutic targets, are still significantly underrepresented in the Protein Data Bank (PDB), with only 3% of their structures resolved. This rarity is due to the difficulty in maintaining their native state in an amphiphilic environment, which complicates their study, especially with classical structural techniques.
This PhD project aims to overcome these challenges by combining the predictive capabilities of AlphaFold with experimental small-angle scattering (SAXS/SANS) data obtained under physiological conditions. The study will focus on the translocator protein TSPO, a key marker in neuroimaging of several serious pathologies (cancers, neurodegenerative diseases) due to its strong affinity for various pharmacological ligands.
The work will involve predicting the structure of TSPO, both in the presence and absence of ligands, acquiring SAXS/SANS data of the TSPO/amphiphile complex, and refining the models using advanced modeling tools (MolPlay, Chai-1) and molecular dynamics simulations. By deepening the understanding of TSPO’s structure and function, this project could contribute to the design of new ligands for diagnostic and therapeutic purposes.
Design of plasmonic nanocomposite membranes for biomolecule detection
Detection of specific small biomolecules amounts is usually challenging. Recently, nanomaterials have provided new materials with interesting optical properties for such an application, especially plasmonic nanomaterials.
In this project, we propose the design of a specific type of nanocomposite made from the incorporation of plasmonic nanoparticles (NPs) within track-etched functionalized polymer membranes. The tuning of the material plasmonic response will be achieved by a controlled in situ NP synthesis directly within the membrane nanopores, through chemical and physico-chemical processes. Especially, the use of radiation (electron beam, ?-rays) to induce the in situ reduction of the metallic precursor will be studied. Ionizing beams (Swift Heavy ions) will also serve to structure the polymer matrix in nanoporous membrane with controlled nanoporosity. The relation between the composite nanostructure and its optical properties will be thoroughly investigated in order to determine the ideal material for biomolecule detection, which will be tested on model molecules such as proteins or virus-like particles (VLPs) in the final part of the project.
Experimental study of boundary layers in turbulent convection by diffusive waves spectroscopy
Turbulent convection is one of the main drivers of geophysical and astrophysical flows, and is therefore a key element in climate modeling. It is also involved in many industrial flows. Transport efficiency is often limited by boundary layers whose nature and transitions as a function of control parameters are poorly understood.
The aim of this thesis will be to set up a convection experiment to probe the dissipation rate in boundary layers in the turbulent regime, using an innovative technique developed in the team: multi-scattered wave spectroscopy.
Calibration of the new High-Angle Time Projection Chambers of the T2K Experiment and Measurement of CP Violation in Neutrino Oscillations
The proposed thesis project focuses on studying neutrino oscillations, a key quantum phenomenon for exploring New Physics beyond the Standard Model. These oscillations, compared between neutrinos and antineutrinos, could shed light on one of the most fundamental questions in particle physics: the origin of the matter-antimatter asymmetry in the Universe.
The T2K experiment, located in Japan, studies these oscillations by generating an intense beam of muon neutrinos (and antineutrinos). This beam is measured at two points: a near detector, used to reduce systematic uncertainties related to the neutrino flux and interaction models, and a far detector (Super-Kamiokande), responsible for measuring the disappearance of muon neutrinos and the appearance of electron neutrinos after oscillations.
The thesis project is divided into two parts. The first part will involve calibrating the new detectors (new time projection chambers using resistive MicroMegas technology) to measure the neutrino energy spectrum and assess the associated systematic uncertainties. The second part will focus on analyzing the newly collected data, allowing for more precise measurements of oscillation parameters, improving the understanding of neutrino-nucleus interactions, and measuring CP violation in neutrino oscillations with 3 sigma significance in the case of maximal violation, as indicated by the latest T2K results, and ultimately 5 sigma in the future Hyper-Kamiokande experiment, which will use the same beam and near detector as T2K.
Topological superconductivity and Fermi surface in spin-triplet superconductors
Topological superconductivity has become a subject of intense research due to its potential for breakthrough in the field of quantum information. Bulk systems are a promising possibility, with candidates found mainly among unconventional superconductors, which are also strongly correlated electron systems. Today, only a few candidate compounds for topological bulk superconductivity exists, and they are mostly uranium-based heavy fermion superconductors. UTe2 is one of the most prominent candidates. The topological properties of the superconductors depends crucially on the topology of the Fermi surface.
In this project we want to set up a novel technique (for our team) relying on a tunnel diode oscillator circuit. This techniques is very sensitive to quantum oscillations, and to be well both to high magnetic fields and to high-pressure studies. First experiments concentrate on the novel superconductor UTe2, where the Fermi surface is only partly known. In further studies the topological properties of the ferromagnetic superconductors UCoGe and URhGe will be revised.
Effects of the 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 in vitro and in vivo models of breast cancer. Two types of molecules, namely an inhibitor of mitochondrial genome maintenance and an inhibitor of the Base Excision Repair pathway, will be tested for radiopotentiation efficacy in the models.
The proposed inhibitors, whether targeting mitochondrial genome maintenance or the BER pathway, 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.).
Sub-critical crack growth in oxide glasses
Material failure is a concern for scientists and engineers worldwide. This includes oxide glasses, which are integral parts of building, electronics, satellites due to multiple advantageous features, including optical transparency, elevated mechanical and thermal properties, chemical durability, biocompatibility and bioactivity, etc. Despite this, oxide glasses have a significate drawback: they are inherently brittle. Oxide glasses are well known to undergo dynamic fracture (crack propagation velocity of ~km/s – as in the case of a glass crashing to the floor and shattering); yet, there is another fracture mode less noticeable that will be studied during this thesis, where crack fronts grow sub-critically. The growth of these crack fronts is aided by environmental parameters including atmospheric humidity and temperature, and the crack front velocity depends on the local stress felt by a crack tip, coined the stress intensity factor.
Currently, our experimental setup tracks the crack front position in time via a tubular microscope equipped with a camera. Post-analysis of images provides the crack front velocity and reveals the environmental limit K_e and region I. However, the current experimental setup cannot capture regions II and III. Several factors play into this limitation: elevated crack front velocity (10e-4 to 1500 m/s), sample size (5×5×25 mm^3), camera acquisition rates, etc.
In recent years, our team has used the potential drop technique to track the crack front velocity when v > 10e-4 m/s in PMMA. This technique involves the deposition of conductive strips on the sample surface. Subsequently, these lines are attached to a high frequency oscilloscope. As the crack front propagates through the sample, the lines are severed resulting in an increase in the electrical resistance. We now wish to adapt this technique to DCDC samples on oxide glasses. The thesis goal is the development and application of the potential drop techniques to DCDC samples. The challenge concerns the spatial temporal resolution (50 µm and 1 ns) in comparison to the crack tip velocity and sample size. The thesis student will take part in all the steps to realize the experiments: designing and depositing patterns (series of strips) on the glass surfaces using a cleanroom, running sub-critical cracking experiments in Region II and III, and analyzing data acquired during the experiment.
Measurement of charm elliptic flow in semi-central Pb-Pb collisions at 5 TeV at CERN with LHCb.
Heavy-ion collisions provide a unique opportunity to study the quark-gluon plasma (QGP), an exotic state of matter where quarks and gluons are no longer confined within hadrons and believed to have existed just a few microseconds after the Big Bang. Charm quarks are among the key probes for investigating the QGP. Indeed, they retain information about their interactions with the QGP, making them essential for understanding the properties of the plasma. The production of charm quarks and their interactions with the QGP is studied through the measurements of hadrons, mesons and baryons, containing at least one charm quark or antiquark, like D0 mesons or Lambda_c baryons. However, the hadronization process—how charm quarks become confined within colorless baryons or mesons—remains poorly understood.
A promising approach to gaining deeper insights into charm hadronization is to measure the elliptic flow of charm hadrons, which refers to long-range angular correlations and is a signature of collective effects due to thermalization. By comparing the elliptic flow of D0 mesons and Lambda_c baryons, researchers can better understand the charm hadronization mechanism, which is sensitive to the properties of the created medium.
To measure elliptic flow, the selected student will develop an innovative method that leverages the full capabilities of the detector. This method, which has never been applied before, provides a more intuitive and theoretically sound interpretation of the results. The candidate will adapt this technique for use with the LHCb detector to measure, compare, and interpret the elliptic flow of Lambda_c charm baryons and D0 mesons with the PbPb samples collected by LHCb in 2024.
The development of surfaces that limit microbial proliferation is a crucial public health issue. In the context of manned flights to remote destinations such as low Earth orbit, the Moon and possibly Mars, biological contamination represents a significant threat to crew health and the preservation of space equipment. The microflora carried by the crew in enclosed habitats constitutes an unavoidable risk, accentuated by prolonged periods of isolation and dependence on closed environment life support systems. In addition to the risks to astronauts' health, biocontamination is known to damage critical equipment on board spacecraft. Furthermore, micro-organisms exposed to the space environment can develop resistance and mutate, transforming benign microbes into pathogens. To mitigate these risks, effective measures, such as filtration systems and self-decontaminating surfaces that limit bacterial proliferation, need to be put in place. The MATISS experiment (2016-2025), in which the SyMMES and PRISM laboratories were involved, explored the use of hydrophobic coatings to reduce biocontamination on board the ISS, but further improvements are needed, in particular to find alternative solutions to perfluorinated agents and antibiotics, but also applicable to a wide range of materials. Such advances could have a wide range of applications beyond space, including food safety (packaging), implantable materials, drinking water treatment, public transport hygiene, etc. The aim of this collaborative thesis between SyMMES and CEA-Leti in Grenoble is to develop sustainable antimicrobial coatings free from harmful substances, by exploring different functionalization methods, such as the formation of self-assembled monolayers, electropolymerization on conductive materials, and in a highly original way by implementing a new cold atmospheric plasma deposition method, suitable for large surfaces, and above all applicable to a wide range of different materials.
Topological and altermagnetic materials: what power can be extracted from the anomalous Hall effect?
The major argument to promote the development of spin electronics and topological materials is the low power dissipation when using spin degrees of freedom and transverse configurations such as Hall configurations. Indeed, in the case of a topological phase, the generated effective magnetic field is expected not to dissipate. However, such an assertion must be the subject of a theoretical description in the context of a realistic electronic device in steady state. The aim of the thesis is to determine the useful power of these devices, in a study that is both experimental and theoretical.
In this context, the definition of the useful power is an open problem. Indeed, the thermodynamics of this type of non-equilibrium system involves cross effects between the degrees of freedom of the electric charge carriers, those of the spin of these carriers, as well as those of the magnetization. The non-equilibrium cross effects are described in a very general way by the famous Onsager reciprocity relations. We have developed a variational method to establish the steady state of a Hall bar and the power dissipated in a load circuit, as a function of the load resistance and the Hall angle. An unexpected result predicts the existence of a maximum ("maximum power transfer theorem"). Preliminary measurements based on the anomalous Hall effect have recently validated the prediction. This experimental confirmation allows us to establish a thesis project that aims to reproduce the measurements on a large set of materials (metals, semiconductors, oxides) and in particular magnetic topological materials, called altermagnetic.
In addition, a ferromagnetic resonance study (called spin pumping) will involve thermoelectric effects, whose dissipative properties, measured on an adjacent load circuit, remain to be determined.