The SNS project, which implies L2C, NEEL, IES, and ICG, intends to develop a broadband optical spin noise detection setup, for probing the spin dynamics of either localized paramagnetic impurities or itinerant carriers in semiconductors. The setup will be tested on Mn spins embedded in CdTe, an ideal model system for broadband optical spin noise detection. The optical setup to be developed will benefit from the recently developed Spin Noise Spectroscopy (SNS) technique. SNS is based on fast sampling of Faraday rotation fluctuations, which faithfully reproduce those of the spins being probed with the laser beam. One gets by FFT a spin noise spectrum equivalent to a spin resonance spectrum. In semiconductors the case of transition metals differs from conduction electrons, by their complex spectra spreading over 1 GHz in case of manganese, the weakness of expected signal, and the necessity to apply a magnetic field of several kOe in order to limit the number of spectral components. This implies a bandwidth of the detection system of several GHz. Thus, the project plans to develop a specific setup, based on either optical heterodyne mixing of the spin noise signal. In addition to the already put forward advantages of SNS over other methods, such as being a “perturbation-free” method, sensitive to a small number of spins, optical heterodyne mixing will extend the spectrum of accessible spin fluctuations in arbitrary magnetic field. Thus this method will outperform Electronic Paramagnetic Resonance (EPR) in terms of sensitivity, but also Optically Detected Magnetic Resonance (ODMR) in terms of bandwidth. It has a strong potential for studying spin noise and spin dynamics in arbitrarily large magnetic field of, not only localized spins, but also itinerant carriers including the regime of short spin relaxation times. The final outcome of the project should be the validation of the method as an optical technique for investigating broadband spin noise of paramagnetic impurities or itinerant carriers in semiconductors. It will be demonstrated by obtaining manganese noise spectra exhibiting fine and hyperfine structures complying with EPR, and will be used for solving some pending questions on Mn spin coherence lifetimes.

Les langasites forment une vaste famille de composés non centro-symétriques transparents. D'abord étudiés comme matériaux lasers, ce sont leurs remarquables propriétés piézoélectriques qui sont exploitées aujourd'hui. De formule générale A3BC3D2O14, ils existent pour une large gamme de cations et leur congruence permet de les fabriquer sous forme de gros monocristaux. Cependant, beaucoup des propriétés de ces composés sont encore très mal connues : les propriétés optiques (luminescence, propriétés nonlinéaires) n'ont été que peu étudiées. On ne sait rien de leurs capacités de bifonctionalité associant ces deux effets. Malgré le potentiel important pour ce type d'application, il n'existe aujourd'hui que très peu de matériaux présentant ces propriétés préparables facilement sous forme de gros cristaux de qualité optique. L'étude de ces propriétés constitue un premier objectif de ce projet. Bien que les sous-réseaux A, B et C des langasites puissent contenir des ions magnétiques, aucune étude de ces propriétés n'a été publiée jusqu'à nos travaux récents. Nous avons montré que le site A occupé par une terre rare magnétique forme un réseau de kagomé. Ces composés sont donc de première importance comme matériaux modèles pour l'étude de la frustration magnétique dans un tel réseau. Les travaux sur la frustration magnétique sont en plein essor et font l'objet de colloques internationaux dédiés. L'étude du réseau kagomé est au centre de cette problématique. Cependant, il n'existe pas de réalisation expérimentale de tels réseaux, du moins dans des composés exempts de désordre et sous forme de gros cristaux utilisables pour les mesures physiques requises. Après avoir réussi la synthèse de cristaux centimétriques en zone fondue, nos premières études expérimentales sur les composés avec A= Pr, Nd ont montré que la frustration induit un état liquide de spin à basse température, dont on rend bien compte par des modélisations théoriques. Un deuxième objectif du projet est donc centré sur l'étude expérimentale et théorique de la frustration du réseau kagomé des langasites, notamment en fonction de la nature de la terre rare (état de spin, anisotropie...). Enfin, nous avons montré que certaines langasites présentaient un ordre magnétique à basses températures: Ba3NbFe3Si2O14 s'ordonne à 25K. Ils permettent donc d'étudier les couplages entre les propriétés liées à la non-centrosymétrie (activité optique, constante diélectrique...) et le magnétisme. C'est là un champ novateur que ces matériaux vont nous permettre d'explorer et qui constitue le troisième objectif du projet. Pour réaliser ce projet ambitieux, il faut d'abord préparer les matériaux. Ceci comporte la synthèse de nouveaux composés et la préparation systématique de gros monocristaux. Pour le magnétisme, langasites d'autres ions de terre rare (par ex. A=Sm, Ce, Gd...) pour l'étude de la frustration ; présentant un ordre magnétique pour l'étude des effets couplés, avec un ou plusieurs sous-réseaux occupés par un ion magnétique. Pour l'optique, dopage par des ions luminescents pour l'étude des effets lasers, et production de gros cristaux de qualité optique pour les mesures ONL et magnéto-optiques. Nous maîtrisons déjà les méthodes de synthèses de céramiques et de cristaux nécessaires à la fabrication de ces matériaux. Les composés produits seront soumis à un ensemble de caractérisations expérimentales: structurales, physiques et optiques. Les partenaires du projet ont une grande complémentarité et une expertise reconnue pour l'ensemble de ces techniques. Des mesures d'effets couplés seront également réalisées, notamment de constante diélectrique et de doublage de fréquence au passage de la transition magnétique, et fonction de la température et du champ. Dans le domaine de la frustration, une étroite collaboration entre expérimentateurs et théoriciens existe depuis longtemps au sein de l'équipe. Les données expérimentales pourront ainsi être constamment confrontées aux modèles théoriques

The project VasKho articulates around the two major theories which revolutionized knot theory over the past twenty years, namely the notions of finite-type invariants and categorification. On one hand, the theory of finite-type invariants, initiated by Goussarov and Vassiliev, provides a unified framework for the study of invariants of knots and knotted objects which includes, in particular polynomial invariants. On the other hand, the theory of categorification considerably enhanced polynomial invariants by interpretating them as the graded Euler characteristic of some richer invariants of homological nature. It includes, for instance, the Khovanov and Heegaard-Floer homologies. There are two main parts in this project. The first one proposes to pursue the study of some of the central problems raised in each of these theories (Tasks 1 and 2). They concern knotted objects, such as usual/virtual/welded links and braids, as well as 3-manifolds. The second part aims at the study of the yet widely open problem of the nature of the connections between finite-type invariants and categorification (Task 3). The project involves four freshly hired Maîtres de Conférence who are all specialized in finite-type invariants or categorification, and aims at creating a french network on these subjects and their interactions.

Gene therapies offer great therapeutic perspectives toward personalized medicine. However, despite considerable efforts, translation of these technologies into clinical applications remains slow and is often hampered by the issue of gene delivery. The intracellular delivery of oligonucleotides is indeed a daunting task due their poor ability to cross biological membranes and their rapid degradation by endogenous nucleases. Viruses are remarkable at performing efficient gene delivery: they ensure chemical stability of the viral gene by its encapsulation within a capsid which actively transports the material to its biological target. Since viral gene delivery can cause severe adverse effects, small molecules able to mimic this process would therefore open new perspectives in gene delivery. The present research project lays out a general methodology to identify synthetic compounds that dynamically encapsulate oligonucleotides and may thus serve as gene carriers. The nanoencapsulation within a synthetic capsid is expected to stabilize oligonucleotides against enzymatic degradation. Furthermore, chemical engineering of the supramolecular carriers will enable active and targeted delivery of unmodified oligonucleotides. The long-term goal of the project is to develop a molecular toolbox for the supramolecular engineering of various oligonucleotides (ssDNA, dsDNA, microRNA, siRNA) with a selective molecular carrier for each application (eg. delivery of antisense DNA to cancer cells) and an extremely straightforward protocol to produce the bioassembly.

"Despite the extensive research on Alzheimer's disease (AD) since its first description in 1907-including the sequencing of Aß peptide in 1984 and cloning of its precursor, APP (ß-amyloid precursor protein), in 1987-little is known about potential ligand interactions with APP, or about any associated ligand-dependent downstream signaling. During the course of the previous ANR ""neuroscience"", P. Mehlen's laboratory identified the guidance cue and trophic factor netrin-1 as a ligand for APP. They showed that this interaction affects APP signaling (including increased transcriptional activity of the APP intracellular domain (AICD)) and they showed that APP is required for netrin-1 function during growth of cortical neurons during development. Of great interest, netrin-1 binding to APP was then shown, both in vitro and in vivo to inhibit the generation of the Aß peptide that is key in AD (Patent CNRS/The Buck Institute for Age Research, n° 00532-050). The identification of netrin-1 as a potential ligand for APP raises many questions regarding the potential role(s) of netrin-dependent APP signal transduction in neuronal development and degeneration but it may have also crucial importance in term of putative therapeutic development. Indeed, it would be of great interest to develop a compound that mimics netrin-1 as a candidate drug against AD. In the current application, two complementary partners (cell biology and animal models versus protein structure) propose to examine some of the critical questions related to the importance of netrin-1 in APP function and to bring this observation closer to drug development. First as a basic question, we would like to assay whether APP behaves as netrin-1 dependence receptor, that is to say that netrin-1, by interacting with APP, inhibits the known pro-apoptotic activity of APP, an activity that we believe is associated, in combination with Aß toxicity, with AD progression. Second we would like to demonstrate that netrin-1 controls not only Ab formation in AD mouse model but also the different hallmarks of the AD pathology. Third, we would like to determine the structure of the interaction APP/netrin-1 in order to define, using in silico screens and an high-through-put screen for small molecules, lead compounds that may mimic netrin-1 or that may increase netrin-1/APP interaction and as consequence may lead to an improvement of AD. The project presented in this ANR “MALZ” call will first provide more basic knowledge to the relative importance of netrin-1 in APP function. It shall (i) describe the nature of the interaction between netrin-1 and APP, (ii) precise whether netrin-1 not only affects Aß formation but also formation of another toxic fragment called C31 generated after caspase cleavage of APP, and (iii) show whether netrin-1 level affects AD phenotype (and not only Aß formation) in an AD mouse model. This basic knowledge shall then be used to predict, design or characterize lead compounds that may in turn inhibit/delay AD progression."