Materials that are simultaneously ferroelectric and ferromagnetic are gaining more and more interest. Such a coupling between ferroelectric and ferromagnetic properties could lead to electric-field switchable magnetization or vice versa. This coupling would lead to totally new possibilities in the design of data storage devices. Unfortunately, the mechanism driving the conventional ferroelectricity such (PbTiO3) is incompatible with the existence of a spontaneous magnetic moment. The off-centering of the Ti-ion in PbTiO3 is stabilized by lowering energy of covalent bond formation, in which charge transfers from the filled oxygen 2p orbitals into the d states of the transition metal ion, which must be empty for this mechanism to be favorable. On the other hand, a partly filled d shell is necessary for magnetism to occur in metal ions which will break the strong covalent bond necessary for ferroelectricity. This is why very few magnetoelectric multiferroics exist. A possible way to avoid this incompatibility was reported by Efremov et al. based on charge-ordered and orbitally-ordered manganites perovskites . From the point of view of ferroelectricity, this kind of charge configuration has notable similarity with the coherent arrangement of electric dipoles discussed commonly in conventional ferroelectric materials (PbTiO3). Unfortunately, these proposed charge-ordered multiferroics in manganites perovskites are unlikely to be of immediate practical use in terms of device applications. The electric polarization is very small and the magnetic ordering is essentially antiferromagnetic. Additionally, the electric and magnetic ordering temperatures are still far below room temperature. Recently, a new origin of ferroelectricity was found in LuFe2O4 based on the specific configuration of charge ordering. In this material, the polar ordering arises from the repulsive property of electron-electron correlations acting on a frustrated geometry. Additionally, giant room temperature magnetodielectric response has also been reported, giving rise to a new generation of multifunctional devices for microelectronics. LuFe2O4 has a hexagonal layered structure (space group R3 ̅m, a = 3.44 Å and c = 25.28 Å). Below 330 K a charge frustration occurs based on the detection of a corresponding superstructure reflection, which indicates a transformation to a three dimensional charge ordering. The goal of this work will be to use the effect of pressure to gain a deep insight into the origin of electronic ferroelectricity in LuFe2O4. The experimental project requires the use of several characterization methods in order to improve our fundamental understanding of the different electrical, structural and electronic process taking place at the nano-, micro- and macro-scopic levels: 1) X-ray and neutron diffraction, 2) EXAFS, 3) Mössbauer spectroscopy and 4) dielectric and piezoelectric measurements. Owing to the complexity of these materials, the use of different techniques is essential for their characterization. Hence, the strength of our project is also related to the complementarities of the three young researchers from the synthesis of the materials, Denis Balitskiy, to the high-pressure characterization, Jérôme Rouquette and to the set-up of a unique experiment of P-T Mössbauer spectroscopy in France, Laurent Aldon. This collaboration should bring new insight in the understanding of this new kind of ferroelectric materials. In conventional ferroelectricity, pressure is found to reduce, and even annihilate for high enough value the electric polarization. As the origin of ferroelectricity in LuFe2O4 is based on electron repulsion, pressure is expected to enhance the polar order. Therefore, the pressure variable appears as the appropriate parameter to investigate LuFe2O4 family of materials in the attempt to increase the TC of this ferroelectric material; one can expect a positive slope of the ferroelectric-paraelectric transition in the P-T space. This knowledge is essential for the optimization of the physical properties of this material, and on the longer term, for the development of new ferroelectric-based materials.

AMNESIA aims to conceive and develop new memory devices for future energy-conscious electronic products. The technical scope is to explore and demonstrate pioneering DRAM solutions in order to fulfill the requirements of these volatile memories in terms of electrical performances and scaling at the 22nm-technology node and beyond. AMNESIA will be focused on novel 1T-DRAMs (capacitor-less single-transistor DRAMs) based on floating-body effects in Silicon-On-Insulator (SOI)-like devices. The work includes the development of programming techniques and matrix array configurations. Innovative solutions for high performance 1T-DRAMs (as compared with the conventional 1T-1C DRAM: transistor + storage capacitor) will be investigated and demonstrated experimentally: reduced bias levels and enhanced reliability, lower power consumption, increased retention time, high temperature operation. AMNESIA will also explore the possibility to enrich the functionalities of the 1T-DRAMs by considering the possibility to store multiple bits and/or by providing a ‘unified’ memory, URAM. URAM uses only one transistor and can be operated indifferently as volatile (DRAM) as well as non-volatile memory (EEPROM, flash). URAM is based on the same principles used in SOI 1T-DRAM while the “non-volatile” charge is stored in a trapping medium. Hence, in a memory array, a single transistor can be allocated indifferently to one or to the other memory function which means that EEPROM and DRAM blocks can be merged for considerable size reduction.

Ion channels are essential components for the activity of a living cell. They are integral membrane proteins that allow specific ions to pass through lipid membranes following a concentration gradient. Several types of ion channels have been described and have been classified depending on their gating properties, their ionic selectivity, and their sensitivity to toxins and pharmacological agents. They have been shown to be involved in many signalling and control processes in the cell as well as in pathologies. In addition, ion channels are viewed as the “next G protein-coupled receptors” in term of potential therapeutic targets. The aim of this proposal is to investigate the properties and the physiological roles of the NALCN cation channel with an emphasis on pancreatic ß-cells. Only few data are available on NALCN to date. Indeed only a dozen research articles are available in PubMed. However, puzzling available data suggest that NALCN is an important player of neuronal excitability and is involved in the sensitivity to volatile anesthetic agents and ethanol, in the regulation of circadian rhythms, locomotor behavious, respiratory rhythm, metabolism, ethanol consumption, and osmoregulation. In addition, genetic studies suggest that NALCN could be a susceptibility locus for bipolar disorder and schizophrenia. We have recently shown that, in addition to the brain, NALCN is also expressed in pancreas in human. This pancreatic expression is restricted to islets of Langerhans in rodents. By using RNA interference and overexpression approaches in the mouse insulin secreting-cell line MIN6, we identified NALCN as the molecular basis of a sodium current previously described in mouse primary beta-cells. This current is activated by acetylcholine through a G protein-independent, TTX-resistant, and atropine-sensitive pathway. In addition, we determined that M3 is the muscarinic receptor subtype (M3R) implicated in NALCN activation through a Src family of tyrosine kinases (SFKs)-dependent pathway. This activation requires the physical association of M3R and NALCN in the same complex. Considering the importance of the cholinergic control in the regulation of glucose-stimulated insulin secretion from pancreatic ß-cells, our published work suggests that NALCN could be an important player of this process. This raises the possibility that NALCN could be a major target to modulate insulin secretion in type-2 diabetes. In the present proposal, we will combine the skills of two complimentary research team in order (i) to investigate the involvement of NALCN in pancreatic ß-cell physiology both in vitro and in vivo, (ii) to determine the molecular basis of the NALCN-containing protein complexes in this cell type, and (iii) to study the biophysical and pharmacological properties of NALCN in recombinant system. Considering our published data as well as our preliminary results, we are convinced that this research program will highlight NALCN as an important player in the regulation of glucose-stimulated insulin secretion by pancreatic ß-cells.

Except for a few species, mammals have an extremely conserved sex determining system. However, within the African pygmy mouse species (genus Mus), we recently uncovered an extraordinary diversity of sex chromosomes: fusions between autosomes and the X and/or Y chromosomes, modifications of sex determinism (XY or XO females), diversification of the Y chromosome, etc. This unique set of features and their phylogenetic proximity with the laboratory mouse make the African pygmy mouse an excellent model to investigate the evolution of mammalian sex chromosomes and sex determination. The SEXYMUS project thus proposes to use pygmy mice as proxies to identify the micro-evolutionary processes involved in X and Y differentiation. Three tasks will be undertaken dealing with different and complementary aspects of sex chromosome evolution. Task 1: Emergence of atypical sex determining systems. Identification of the genetic basis and the selective forces at play The mutation causing male-to-female sex reversal in M. minutoides will be investigated by cytogenomic and molecular approaches. Preliminary results have already identified the X chromosome as the target of the mutation. This study is expected to contribute to the identification of new genes involved in the sex determination pathway in mammals in general, and may highlight new gene candidates of pathological sex reversals in human in particular. Understanding the evolution of such aberrant sexual systems is one of the main goals of evolutionary biology. As these modifications are considered as highly deleterious, selective mechanisms are expected to have favored their diffusion. These will be explored by a multidisciplinary study integrating different approaches: the nature of the genes involved in the chromosomal changes will be established (cytogenomics), their rate and mode of evolution measured (sequencing, RT-PCR), phenotypic correlations identified (behaviour), and finally evolutionary predictions tested (computer modelling). Task 2: Y chromosome degeneration. Estimation of the mode and tempo of genetic erosion. It is universally accepted that the Y chromosome degenerates progressively. However, its rate of degeneration is vigorously debated, as well as its dynamics. The morphology of the Y chromosome of African pygmy mice is extremely diverse, varying from a normal-sized to a minute chromosome, and even to a complete loss of the Y chromosome described in one species. These results suggest fast genetic erosion. Hence, a comparative genomic approach of several Y-linked genes between different species/populations of pygmy mice will provide a micro-evolutionary insight into the dynamics of mammalian Y degeneration. Task 3: Origin and evolution of neo-sex chromosomes. “Sexualisation” of autosomes In sex-autosome fusions, parts of the autosomal genome, which were previously inherited from both parents, become linked to the sex chromosomes, and are thus only transmitted to one of the two sexes. These modifications lead to dramatic changes of the selective regime acting on these regions that are expected to influence the evolution of their gene content (sexualisation), gene expression (differentiation between sexes), and sequences (rapid evolution under positive selection, or degeneration after the suppression of recombination). We will test these theoretical predictions by cytogenomic and molecular analyses in one species carrying a neo-Y chromosome. The same approach will be performed on an exceptional case population within M. minutoides where almost (if not all) females are XY, leading to the quasi-complete suppression of recombination in a X chromosome.