ERC FUNDED PROJECTS

We propose the development of novel nanodevices, such as nanoscale bridges and nanovectors, based on functionalized carbon nanotubes (CNT) for manipulating neurons and neuronal network activity in vitro. The main aim is to put forward innovative solutions that have the potential to circumvent the problems currently faced by spinal cord lesions or by neurodegenerative diseases. The unifying theme is to use recent advances in chemistry and nanotechnology to gain insight into the functioning of hybrid neuronal/CNT networks, relevant for the development of novel implantable devices to control neuronal signaling and improve synapse formation in a controlled fashion. The proposal s core strategy is to exploit the expertise of the PI in the chemical control of CNT properties to develop devices reaching various degrees of functional integration with the physiological electrical activity of cells and their networks, and to understand how such global dynamics are orchestrated when integrated by different substrates. An unconventional strategy will be represented by the electrical characterization of micro and nano patterned substrates by AFM and conductive tip AFM, both before and after neurons have grown on the substrates. We will also use the capability of AFM to identify critical positions in the neuronal network, while delivering time-dependent chemical stimulations. We will apply nanotechnology to contemporary neuroscience in the perspective of novel neuro-implantable devices and drug nanovectors, engineered to treat neurological and neurodegenerative lesions. The scientific strategy at the core of the proposal is the convergence between nanotechnology, chemistry and neurobiology. Such convergence, beyond helping understand the functioning and malfunctioning of the brain, can stimulate further research in this area and may ultimately lead to a new generation of nanomedicine applications in neurology and to new opportunities for the health care industry.

2 500 000 €

Start date: 2009-02-01, End date: 2014-01-31

CD8 T lymphocytes have a fundamental role in ensuring the control of different types of intracellular pathogens including bacteria, parasites and most viruses. This control may fail due to several reasons. The current aggressive anti-cancer therapies (or rarely certain congenital immune deficiencies) induce CD8 depletion. After bone-marrow transplantation, long time periods are required to ensure T cell reconstitution particularly in the adult. This long lag-time is due to the long-time periods required for hematopoietic precursors to generate T lymphocytes and to a thymus insufficiency in the adult. However, even when CD8 T cells are present CD8 immune responses are not always adequate. Certain chronic infections, as HIV, induce CD8 dysfunction and it is yet unclear how to generate efficient CD8 memory responses conferring adequate protection. To address these questions this project aims 1) To find strategies ensuring the rapid reconstitution of the peripheral and the gut CD8 T cell compartments a) by studying the mechanisms involved HSC division and T cell commitment; b) by isolating and characterizing progenitors we previously described that are T cell committed and able of an accelerated CD8 reconstitution c) by developing new strategies that may allow stable thymus transplantation and continuous thymus T cell generation. 2) To determine the mechanics associated to efficient CD8 memory generation a) by evaluating cellular modifications that ensure the efficient division and the remarkable accumulation and survival of CD8 T cells during the adequate immune responses as compared to inefficient responses b) by studying CD8 differentiation into effector and memory cells in both conditions. These studies will use original experiment mouse models we develop in the laboratory, that allow to address each of these aims. Besides state of the art methods, they will also apply unique very advanced approaches we introduced and are the sole laboratory to perform.

1 969 644 €

Start date: 2009-02-01, End date: 2014-05-31

One of the major outcomes of recent studies on the formation of the Solar System is the reconnaissance of the fundamental importance of processes which took place during the first 10 thousands to 2 or 3 millions years of the lifetime of the Sun and its accretion disk. Astrophysical observations in the optical to infrared wavelengths of circumstellar disks around young stars have shown the existence in the inner disk of high-temperature processing of the dust. X-ray observations of T-Tauri stars revealed that they exhibit X-ray flare enhancements by several orders of magnitude. The work we have performed over the last years on the isotopic analysis of either solar wind trapped in lunar soils or of Ca-, Al-rich inclusions and chondrules from primitive chondrites, has allowed us to link some of these astrophysical observations around young stars with processes, such as irradiation by energetic particles and UV light, which took place around the T-Tauri Sun. The aim of this project is to make decisive progress in our understanding of the early solar system though the development of in situ high-precision isotopic measurements by ion microprobe in extra-terrestrial matter. The project will be focused on the exploration of the variations in the isotopic composition of O and Mg and in the concentration of short-lived radioactive nuclides, such as 26Al and 10Be, with half-lives shorter than 1.5 millions years. A special emphasis will be put on the search for nuclides with very short half-lives such as 32Si (650 years) and 14C (5730 years), nuclides which have never been discovered yet in meteorites. These new data will bring critical information on, for instance, the astrophysical context for the formation of the Sun and the first solids in the accretion disk, or the timing and the processes by which protoplanets were formed and destroyed close to the Sun during the first 2 million years of the lifetime of the Solar System.

1 270 419 €

Start date: 2009-01-01, End date: 2013-12-31

Neuroscience is one of the fastest-developing areas of science, but it is fair to say that we are still far from understanding how the brain produces subjective experience. For example, simple questions about the origin of thought, imagination, social interaction, or feelings lack even rudimentary answers. We have learnt much about the workings of individual cells and synapses, but psychological phenomena cannot be understood only at this level. These phenomena all emerge from interactions between large numbers of diverse cells in intermingled neural circuits. A major obstacle has been the absence of concepts and tools for investigating neural computation at the circuit level. The aim of this proposal is to combine new transgenic methods for cell type-specific intervention with large-scale multisite single-cell recording to determine how a basic cognitive function self-localization is generated in a functionally well-described mammalian neural circuit. We shall use our recent discovery of entorhinal grid cells as an access ramp. Grid cells fire only when the animal moves through certain locations. For each cell, these locations define a periodic triangular array spanning the whole environment. Grid cells co-exist with other entorhinal cell types encoding head direction, geometric borders, or conjunctions of features. This network is thought to form an essential part of the brain s coordinate system for metric navigation but the detailed wiring, the mechanism of grid formation, and the function of each morphological and functional cell type all remain to be determined. We shall address these open questions by measuring how dynamic spatial representation is affected by transgene-induced activation or inactivation of the individual components of the circuit. The endeavour will pioneer the functional analysis of neural circuits and may, perhaps for the first time, provide us with mechanistic insight into a non-sensory cognitive function in the mammalian cortex.

2 499 112 €

Start date: 2009-01-01, End date: 2013-12-31