ERC FUNDED PROJECTS

Traffic-related air pollution is an important environmental problem that may affect neurodevelopment. Ultrafine particles (UFP) translocate to the brains of experimental animals resulting in local proinflammatory overexpression. As the basic elements for thinking are acquired by developing brains during infancy and childhood, susceptibility may be elevated in early life. We postulate that traffic-related air pollution (particularly UFPs and metals/hydrocarbons content) impairs neurodevelopment in part via effects on frontal lobe maturation, likely increasing attention-deficit/hyperactivity disorder (ADHD). BREATHE objectives are to develop valid methods to measure children's personal UFP exposure and to develop valid neuroimaging methods to assess correlations between neurobehavior, neurostructural alterations and particle deposition in order to reveal how traffic pollution affects children¿s exposure to key contaminants and brain development, and identify susceptible subgroups. We have conducted general population birth cohort studies providing preliminary evidence of residential air pollution effects on prenatal growth and mental development. We aim to demonstrate short and long-term effects on neurodevelopment using innovative epidemiological methods interfaced with environmental chemistry and neuroimaging following 4000 children from 40 schools with contrasting high/low traffic exposure in six linked components involving: repeated psychometric tests, UFP exposure assessment using personal, school and home measurements, gene-environment interactions on inflammation, detoxification pathways and ADHD genome-wide-associated genes, neuroimaging (magnetic resonance imaging/spectroscopy) in ADHD/non-ADHD children, integrative causal modeling using mathematics, and replication in 2900 children with neurodevelopment followed from pregnancy. We believe the expected results will have worldwide global planning and policy implications.

2 499 230 €

Start date: 2011-08-01, End date: 2016-07-31

Networks have been studied in depth for several decades, but one aspect has received little attention: Interference. Most networks use clever algorithms to avoid interference, and this strategy has proved effective for traditional supply-chain or wired communication networks. However, the emergence of wireless networks revealed that simply avoiding interference leads to significant performance loss. A wealth of cooperative communication strategies have recently been developed to address this issue. Two fundamental roadblocks are emerging: First, it is ultimately unclear how to integrate cooperative techniques into the larger fabric of networks (short of case-by-case redesigns); and second, the lack of source/channel separation in networks (i.e., more bits do not imply better end-to-end signal quality) calls for ever more specialized cooperative techniques. This proposal advocates a new understanding of interference as computation: Interference garbles together inputs to produce an output. This can be thought of as a certain computation, perhaps subject to noise or other stochastic effects. The proposed work will develop strategies that permit to exploit this computational potential. Building on these ``computation codes,'' an enhanced physical layer is proposed: Rather than only forwarding bits, the revised physical layer can also forward functions from several transmitting nodes to a receiver, much more efficiently than the full information. Near-seamless integration into the fabric of existing network architectures is thus possible, providing a solution for the first roadblock. In response to the second roadblock, computation codes suggest new computational primitives as fundamental currencies of information.

1 776 473 €

Start date: 2011-05-01, End date: 2016-04-30

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells release granzyme and perforin from cytotoxic granules into the immune synapse to induce apoptosis of target cells that are either virus-infected or cancerous. Granzyme A activates a caspase-independent apoptotic pathway and induces mitochondrial damage characterized by superoxide anion production and loss of the mitochondrial transmembrane potential, without disrupting the integrity of the mitochondrial outer membrane; while causing single-stranded DNA damage. GzmB induces both caspase-dependent and caspase-independent cell death. In the caspase-dependent pathway, mitochondrial functions are altered as evidenced by the loss of mitochondrial transmembrane potential and the generation of reactive oxygen species (ROS). The mitochondrial outer membrane (MOM) is disrupted, resulting in the release of apoptogenic factors. To date, research on mitochondrial-dependent apoptosis has focused on mitochondrial outer membrane permeabilization (MOMP) however whether the generation of ROS is incidental or essential to the execution of apoptosis remains unclear. Like human GzmA, human GzmB promotes cell death in a ROS-dependent manner. Preliminary data suggest that human GzmB can induce ROS in a MOMP-independent manner as Bax and Bak double knockout MEF cells treated with human GzmB and perforin still display a robust ROS production and dye in an ROS-dependent manner. Since GzmA and GzmB induce cell death in a ROS-dependent manner, we hypothesize that oxygen free radicals are central to the execution of programmed cell death induced by the cytotoxic granules. Therefore, the goal of this proposal is to dissect the key molecular events triggered by ROS that lead to Citotoxic Tcell-induced target cell death. A combination of biochemical, genetic and proteomic approaches in association with Electron Spin Resonance (ESR) spectroscopy methodology will be used to unravel the essential role ROS play in CTL-mediated killing.

1 500 000 €

Start date: 2011-05-01, End date: 2016-04-30

Future electronic systems will be soft and elastic. I propose to explore the materials, technology and integration of stretchable electronic systems, which will transform at will, evenly coat a spherical lens, or smoothly interface with a delicate biological organ. Electronics will be anywhere as well as everywhere. The proposed programme has the potential to emulate yet another revolution in the microelectronics industry and trigger transformations in the biomedical sector. The ESKIN programme is an ambitious and highly interdisciplinary endeavour requiring expertise at the frontier of engineering, material sciences, biotechnology and neuroscience. Stretchability in an electronic system is its ability to negotiate mechanical deformations without letting them interfere with its electrical functionality. This is a novel and challenging demand on electronic device technology, which has, to date, mainly pushed for smaller scale fabrication and increased performance. Furthermore the natural compliance of biological tissues and cells calls for softer electronic biomedical interfaces. Overcoming the hard to soft mechanical mismatch will, without doubt, open up new horizons in biomedical research and its related industries. The manufacture of stretchable electronic skins will then require working out the underlying science and technology for active device materials on soft, elastic substrates. This capability will further be implemented to demonstrate various soft and elastic electronic systems ranging from stretchable displays to long-term neural implants. My philosophy is to exploit as much as possible current micro/nanofabrication techniques available for hard surfaces but to tailor them to soft surfaces , optimizing and improving them where needed, in order to ensure rapid transition to worldwide distributed consumer and healthcare products.

1 499 738 €

Start date: 2011-03-01, End date: 2016-02-29