Scaling of cytoskeletal organization in relation to cell size and function
Each cell type, defined by its function and state, is characterized by a specific size range. Indeed, cell size within a specific cell type displays a narrow distribution that can vary from as much as several orders of magnitude between smaller cells, such as red blood cells, and large muscle cells. Interestingly, this size characteristic is essentially maintained during the life cycle of an individual and highly conserved among mammals. Altogether, these features suggest that maintaining “the right size” for a given cell could play an important role in performing its function.
The actin cytoskeleton, that can form different stable while dynamic intracellular architectures, plays a major role in the structural plasticity of cells in response to changes in shape and size. Our recent work suggests that actin networks developed within a cell scale with the actual size and volume of the cell. However, how cells adapt the turnover and organization of their numerous structures assembled from a limiting pool of actin monomers remains to be understood.
In this project, we thus propose to study the organization and dynamics of actin networks in selected cell types displaying distinct sizes. In particular, our study will focus on characterizing the impact of such networks organization/dynamics on different cellular functions such as cell migration or adaptability to environmental cues. The feedback between cytoskeletal architecture dynamics, cell size and function will also be addressed by perturbing the organization and dynamics of the actin cytoskeleton in these cells.
PRObablistic on-edge learning for SPINtronic-based neuromorphic systems
The hired joint UGA – KIT PHD candidate should be able to cover the work of the workpackage 1 and 2. He/she will also participate to technical meetings and have a good understanding on how the tasks of the other technical workpackages are executed, mainly by the partners with internal effort. As a whole, the PHD candidate will develop and optimize compact Computing in Memory architectures, provide high level models for further integration in large scale designs, perform validation of all proofs of concepts of new architectural implementations. He/she will be involved also in the design of algorithmic implementations of Bayesian Neural Networks adapted to the architecture. More in details, he/she will work on the following directions:
Design and optimization of the probabilistic neural networks, will be executed mostly in SPINTEC Laboratory in Grenoble, that will include:
1. full design stack of hardware accelerator without selector transistor for frequent Read and Write operations.
2. Design and validate an innovative architectural approach able to compensate for sneaky paths phenomena.
3. High-level modeling of the full crossbar architecture that includes the stochastic component.
4. Propose a full simulation and validation flow scalable to scaled to realistic architecture size and parameters that implement Bayesian tasks.
5. Perform Delay, power consumption and area overhead figures of merit
Study of the links between the dysregulations of metabolism and epigenetics marks in Huntington’s disease
We want to focus on epigenetic dysregulation in Huntington’s Disease (HD), a pathogenic mechanism implicated in accelerated aging of striatal neurons. Specifically, we will investigate the interplay between altered energy metabolism and epigenetic impairment in HD striatal neurons to identify new targets/pathways for disease-modifying intervention. We aim to obtain detailed maps of histone post-translational modifications (PTMs), especially of methylations, acetylation and the recently described lactylation, which might be critical in the HD brain. Indeed, these PTMs are tightly regulated by the metabolic status of the cells. We will use proteomics which is the best suited approach to identify and quantify multiple protein PTMs. We consider working on the striatum of WT, R6/1 transgenic mice and the more progressive Q140 knock in model at various stages of disease, to assess evolution of histone PTMs and metabolism with aging. Additionally, to get a dynamic view of the links between metabolic and epigenetic imbalance in HD, we will inject intraperitoneally HD mice and controls with 13C-glucose and analyze over a time course the incorporation of 13C into histone PTMs. Finally, acetyl-CoA, the precursor for histone lysine acetylation, has been shown to be locally produced in the nucleus, by either acetyl-CoA synthetase 2 (ACSS2), ATP-citrate lyase (ACLY) or the pyruvate dehydrogenase complex. Regarding lactylation, it is currently unknown where, and by which enzymes, the pool of lactate used for modifying histone lysines by lactylation is produced. ACSS2 is a very good candidate, as it can catalyze the production of acyl-CoA molecules from the corresponding short chain fatty acids (SCFA). To address the question of the production of metabolites in the vicinity of chromatin in striatal cells, we will use epigenomics (ChIPseq or CUT&tag) to get the genomic distribution of ACSS2 and ACLY and compare it to distributions of acetyl and lactyl histone marks.
Superconducting Devices in Silicon
The project focuses on the study of superconducting devices with silicon as a semiconductor. Those include standard silicon transistors with superconducting source and drain contacts and superconducting resonators. The common properties is the superconducting material which is elaborated with the constrain of being compatible with the silicon CMOS technology.
In the actual situation of the project, devices with CoSi2, PtSi and Si:B superconducting contacts have been fabricated using the 300 mm clean room facility at the LETI and in collaboration with our partners at Uppsala university and C2N Paris Saclay. The main issue is now to characterize the electronic transport properties at very low temperature.
Condensates and Chromatin: How Phase Separation Shapes Plant Temperature Responses
Plants must adapt their development to environmental conditions, including rising temperatures due to climate change. Heat stress significantly impacts plant physiology, and to mitigate these effects, plants have evolved heat shock responses (HSR), with Heat Shock Factor A1a (HSFA1a) serving as a master regulator in Arabidopsis thaliana. Under nonstress conditions, HSFA1a remains cytosolic and inactive, bound to heat shock proteins (HSPs). Heat stress triggers HSP dissociation, enabling HSFA1a nuclear translocation, trimerization, chromatin binding, and activation of stress-responsive genes. Recent studies reveal that HSFA1a might act as a pioneer transcription factor to access closed chromatin regions and initiate HSR. Additionally, preliminary findings also suggest that HSFA1a undergoes liquid-liquid phase separation (LLPS) to form nuclear condensates that regulate gene expression. This project aims to 1) explore how temperature affects HSFA1a structure and oligomerization, 2) investigate LLPS of HSFA1a with and without DNA, 3) characterize HSFA1a pioneer activity, and 4) determine the physiological importance of LLPS in HSR.
Towards a detailed understanding of the regulation of gene expression by acetylation and lactylation of histone proteins
In eukaryotic cells, DNA is wrapped around histone proteins to form chromatin. Dynamic modification of histones by various chemical structures enables fine regulation of gene expression. Alterations in these complex regulatory mechanisms are at the root of many diseases. Histone lysine acetylation is known to induce gene expression. Other structures can be added to histones, whose effects on transcription remain largely to be elucidated. Most of them, like lactylation discovered in 2019, depend on cellular metabolism. We have begun to study lactylation in the context of murine spermatogenesis. This process of cellular differentiation is a model of choice for studying the regulation of transcription, due to the dramatic changes in chromatin composition and the gene expression program. We have generated novel epigenetic profiles consisting of the genome-wide distribution of acetylated and lactylated marks on three histone H3 lysines. The aim of this thesis is to contribute to the deciphering of the “histone code”, firstly by studying the role of lactylations on the transcriptional program. Secondly, the prediction of chromatin states will be refined by integrating our new data with existing epigenomic data at the two studied cellular stages, within neural network models.
Theoretical studies of orbitronic and spin-orbit phenomena in heterostructures comprising van der Waals materials, metals and oxides
The proposed PhD thesis aims at finding the best-unexplored combinations of transition metals, oxides and 2D materials (transition metal dichalcogenides, 2D magnets, graphene…) to help optimizing and providing scientific underpinnings of next generation energy efficient spintronic storage and memory devices based on emerging fields of spin-orbitronics and orbitronics. The latter is a fascinating new field of research that exploits orbital currents and their interaction with spin currents mediated by spin-orbit coupling.
Namely, using first principles calculations combined with tight-binding approach and linear response theory, we will screen the potential of aforementioned heterostructures not only for spin-orbit phenomena such as Dzyaloshinskii-Moriya interaction (DMI), perpendicular magnetic anisotropy (PMA) and spin-charge interconversion based on Rashba and Rashba-Edelstein effects (REE), but also focus on Orbital Rashba Edelstein Effect (OREE). Furthermore, the mechanisms of control of these phenomena via external stimuli (strain, external electric and magnetic fields) will be investigated as well. These studies will help finding optimal material combination to tune DMI, PMA and spin-charge interconversion efficiency to help optimizing spintronic devices making thereby a significant contribution to the development of sustainable microelectronics.
The PhD will be based on a multiscale approach including ab initio, tight-binding and atomistic approaches thus highly motivated candidate with a good background in solid state physics, condensed matter theory and numerical simulations is required. He/she will perform his/her calculations on Spintec computational cluster nodes using first-principles packages based on density functional theory (DFT) combined with other simulation codes/tools. Results obtained will be carefully analyzed with the possibility of publication in international scientific journals. Strong collaboration with labs in France (CEA/LETI, Laboratoire Albert Fert (CNRS,Thales), Aix-Marseille Univ…) and abroad (ICN2-Barcelona, PGI Forschungszentrum Jülich, Osaka University) are previewed.
Deciphering the roles of surface chemistry and multi-scale structuration in controlling the storage performances of graphene-based supercapacitors
Summary of the project: The project’s objective is to advance fundamental research by elucidating the intrinsic relationship between the properties of graphene-based material and their electrochemical storage performances in supercapacitor cells, thanks to the combination of basic and advanced characterization techniques, particularly adapted to the investigation of the evolutions of the surface chemistry and multi-scale structure upon cycling. These findings will enable to provide a multi-scale understanding of storage mechanism and will help to further design materials with enhanced storage properties.
Two-qubit gate made with Germanium heterostructures
We are working on germanium spin qubits, a promising and versatile base material to engineer spin quantum bits. In these "heterostructures", holes are hosted in a germanium layer sandwiched between two layers of silicon/germanium. These holes exhibit a very high mobility and unlike electron spins which are only sensitive to magnetic fields, hole spins can be manipulated by an electric field, ie by voltages on a gate. The all-electrical control comes with its own drawback: spins become sensitive to electrical, and therefore charge noise in the devices. The germanium heterostructures feature metallic top gates that mostly screen the charge noise from defects they covered; however, in regions not covered by top gates, unscreened charges are responsible for charge noise limiting the coherence time.
We are acquiring a world unique cleanroom equipment combining atomic layer deposition and atomic layer etching, which will allow for the development of original structures where the gates are penetrating deep within the heterostructure, in order to circumvent the effect of these lone charges on the surface in the case of top gates. With this novel scheme, the definition and manipulation of quantum dots will be extremely simplified, and we plan to obtain two-qubit gate devices well within the scope of this PhD.
Strain field imaging in semiconductors: from materials to devices
This subject addresses the visualization and quantification of deformation fields in semiconductor materials, using synchrotron radiation techniques. The control of the deformation is fundamental to optimize the electronic transport, mechanical and thermal properties.
In a dual technique approach we will combine the determination of the local deviatoric strain tensor by scanning the sample under a polychromatic nano beam (µLaue) and a monochromatic full field imaging with a larger beam (dark field x ray microscopy, DFXM).
New developments of the analysis will be focused on 1/ the improvement of the accuracy and speed of the quantitative strain field determination, 2/ the analysis of strain gradient distributions in the materials, and 3/ the determination of the dynamic strain field in piezoelectric materials through stroboscopic measurements. To illustrate these points, three scientific cases corresponding to relevant microelectronic materials of increasing complexity will be studied:
1- Static strain fields surrounding metallic contacts, such as high-density through silicon vias (TSV) in CMOS technology.
2- Strain gradients in Ge/GeSn complex heteroepitaxial structures with compositional variations along the growth direction.
3- Dynamical strain in LiNbO3 surface acoustic wave resonators with resonance frequency in the MHz range bulk
Establishing this approach will mean moving a step forward towards more efficient microelectronics and strain engineering.