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 TERMINÉ 

The LHC Battle for Naturalness on the Top Charm Front (TOPCHARM)

Date du début: 1 juil. 2014, Date de fin: 30 juin 2019,

Now that a Higgs-like particle has been discovered naturalness becomes the most pressing and fundamental question within the reach of the Large Hadron Collider (LHC). The main contribution that destabilises the electroweak scale comes from a top-quark loop. The key for addressing the naturalness problem is thus identifying the top partners that are stabilizing the weak scale.We consider the follo ...
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 TERMINÉ 

Cellular Destruction Mechanisms that Create New Lives (SPERMDESTRUCT)

Date du début: 1 mai 2014, Date de fin: 30 avr. 2019,

Apoptosis, the major form of programmed cell death (PCD), is executed by caspases. However, activation of caspases can also promote a variety of vital cellular processes. Furthermore, cell death can sometimes proceed in the absence of apoptotic caspases by triggering alternative cell death (ACD) pathways. The main goal of my proposal is to delineate the molecular mechanisms, pathways and component ...
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 TERMINÉ 

microRNAs confer robustness to adult beta–cell identity (MIRNABETAIDENTITY)

Date du début: 1 avr. 2014, Date de fin: 31 mars 2019,

Normal physiology depends on defined functional output of differentiated cells. A century of Developmental–Biology studies revealed diverse mechanisms for differentiation, however once ‘terminally’ differentiated, cells are thought to naïvely stay put. However differentiated cells are surprisingly fragile, for example, phenotypic collapse and de–differentiation of β–cells was recently discovered i ...
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 TERMINÉ 

Control of translation efficiency in proliferating and differentiated mammalian cells (TRNAPROLIF)

Date du début: 1 avr. 2014, Date de fin: 31 mars 2019,

Translation maps the transcriptome onto the proteome. It is regulated at the initiation levels and also by mRNA secondary structure, and – our current focus – by the interplay between the mRNA and tRNA pools. Although a lot is known about the mechanics of translation, its effects on physiology, particularly on proliferation and differentiation in mammals presents major open questions.tRNAProlif of ...
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 1

 TERMINÉ 

Neutral Quasi-Particles in Mesoscopic Physics (NEUTRAL)

Date du début: 1 mars 2014, Date de fin: 28 févr. 2019,

I propose to study ‘neutral excitations’ in 2d and 1d electronic systems. Such excitations, rarely studied, are unique since they are chargeless but may carry energy. Being byproducts of electron interaction, they come in a few flavors: (i) Downstream modes in composite edge channels of the integer quantum Hall effect (IQHE) regime; (ii) Upstream modes in the fractional quantum Hall effect (FQH ...
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 TERMINÉ 

Systematic analysis of the molecular mechanisms underlying axon growth during development and following injury (AXONGROWTH)

Date du début: 1 mars 2014, Date de fin: 28 févr. 2019,

Axon growth potential declines during development, contributing to the lack of effective regeneration in the adult central nervous system. What determines the intrinsic growth potential of neurites, and how such growth is regulated during development, disease and following injury is a fundamental question in neuroscience. Although multiple lines of evidence indicate that intrinsic growth capabilit ...
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 1

 TERMINÉ 

Deciphering the molecular language orchestrating host-microbiome interactions and their effects on health and disease (META-BIOME)

Date du début: 1 mars 2014, Date de fin: 28 févr. 2019,

The gastrointestinal tract hosts the microbiome, one of the highest microbial densities on earth. Diverse host-microbiome interactions influence a multitude of physiological and pathological processes, yet the basic mechanisms regulating host-microbiome interactions remain unknown. Deciphering the codes comprising the host-microbiome communication network and factors initiating loss of homeostasis ...
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 1

 TERMINÉ 

Deciphering the code of gene regulation using massively parallel assays of designed sequence libraries (GENEREGULATION)

Date du début: 1 mars 2014, Date de fin: 28 févr. 2019,

Many gene expression changes that are associated with disease states have in turn been linked to changes in the genes’ regulatory regions. However, without a ‘regulatory code’ that informs us how DNA sequences determine expression levels, we cannot predict which sequence changes will affect expression, by how much, and by what mechanism.Here, we aim to arrive at a mechanistic and quantitative unde ...
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 1

 TERMINÉ 

Developing novel therapies for systemic disorders by regulating Nitric Oxide (NO) substrates' availability (NO-DISEASE)

Date du début: 1 mars 2014, Date de fin: 28 févr. 2019,

Nitric oxide (NO) is an essential signalling molecule for diverse physiological and disease processes. The current paradigm of how NO production is regulated focuses at the level of nitric oxide synthase (NOS), with respect to substrate and co-factor availability and the precise spatial and temporal arrangement of protein complexes. However, the respective unique or combined genetic deficiencies ...
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 1

 TERMINÉ 

Guided Nanowires: From Growth Mechanism to Self-Integrating Nanosystems (GUIDEDNW)

Date du début: 1 févr. 2014, Date de fin: 31 janv. 2019,

The large-scale assembly of nanowires (NWs) with controlled orientation on surfaces remains one challenge toward their integration into practical devices. A recent paper in Science from the PI’s group reported the guided growth of millimeter-long horizontal NWs with controlled orientations on crystal surfaces. The growth directions and crystallographic orientation of GaN NWs are controlled by thei ...
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 1

 TERMINÉ 

Principles of biomolecular networks (PNET)

Date du début: 1 févr. 2014, Date de fin: 31 janv. 2019,

Cells process information using biochemical circuits of interacting proteins and genes. We wish to define principles guiding the design of those circuits. The interplay between variability and robustness is of key interest to us. Bio-molecular processes are stochastic, environmental conditions fluctuate, and sequence polymorphisms are abundant. How is variability buffered to maintain reproducible ...
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 1

 TERMINÉ 

Optical dissection of prefrontal neuromodulation: from synapses through networks to behavior (OPTONEUROMOD)

Date du début: 1 févr. 2014, Date de fin: 31 janv. 2019,

The neocortex is organized into neural circuits that perform distinct computations, from sensory processing and motor control to memory, learning and language. Neuromodulatory systems projecting to the neocortex exert a powerful influence on cortical computations through neurotransmitters such as acetylcholine, monoamines and neuropeptides. The prefrontal cortex (PFC), a cortical region required f ...
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 1

 TERMINÉ 

Chemistry of the Quantum Kind (QUCC)

Date du début: 1 janv. 2014, Date de fin: 31 déc. 2018,

There has been a long-standing quest to observe chemical reactions at low temperatures where reaction rates and pathways are governed by quantum mechanical effects. So far this field of Quantum Chemistry has been dominated by theory. The difficulty has been to realize in the laboratory low enough collisional velocities between neutral reactants, such that the quantum wave nature could be observed. ...
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 1

 TERMINÉ 

Quantum Metrology with Trapped Ions (IONOLOGY)

Date du début: 1 janv. 2014, Date de fin: 31 déc. 2018,

We propose a quantum algorithmic approach to metrology and its implementation using trapped-ion qubits. Active decoherence suppression methods such as decoherence-free subspaces, Quantum error-correction codes and dynamic decoupling will be used to reduce the effect of noise while amplifying a measured signal, thus improving on the measurement signal-to-noise ratio. An ion trap architecture that b ...
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 1

 TERMINÉ 

High-Dimensional Phenomena and Convexity (DIMENSION)

Date du début: 1 janv. 2013, Date de fin: 31 déc. 2018,

High-dimensional problems with a geometric flavor appear in quite a few branches of mathematics, mathematical physics and theoretical computer science. A priori, one would think that the diversity and the rapid increase of the number of configurations would make it impossible to formulate general, interesting theorems that apply to large classes of high-dimensional geometric objects. The underlyi ...
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 2

 TERMINÉ 

Lipoproteins and angiogenesis: A new look at an old problem (LIPINTOECTION)

Date du début: 1 déc. 2013, Date de fin: 30 nov. 2018,

Cardiovascular diseases (CVDs) are the leading cause of death throughout the world. Elevated Low Density Lipoprotein (LDL) is a well-known cardiovascular risk factor and endothelial (ECs)-lipoprotein (LIPs) interactions underlie the initiation and progression of atherogenesis, thrombosis and other CVDs.The endothelium is a monolayer of cells that segregates the vascular contents from adjacent tiss ...
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 1

 TERMINÉ 

Single cell heterogeneity in the mammalian liver (LIVHET)

Date du début: 1 nov. 2013, Date de fin: 31 oct. 2018,

The mammalian liver performs critical functions for maintaining metabolic homeostasis. It regulates the body’s glucose and lipid stores, detoxifies blood, and produces bile among a host of other functions. The liver achieves this diversity through the collective behaviour of heterogeneous hepatocytes operating in highly structured microenvironments. Understanding the design principles of the liver ...
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 1

 TERMINÉ 

Multi-Dimensional Study of non Abelian Topological States of Matter (MUNATOP)

Date du début: 1 oct. 2013, Date de fin: 30 sept. 2018,

Non-abelian topological states of matter are of great interest in condensed matter physics,both due to their extraordinary fundamental properties and to their possible use for quantumcomputation. The insensitivity of their topological characteristics to disorder, noise,and interaction with the environment may lead to realization of quantum computers withvery long coherence times. The realization o ...
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 1

 TERMINÉ 

Mutational and Functional Analysis of the Melanoma Genome (MELGEN)

Date du début: 1 oct. 2013, Date de fin: 30 sept. 2018,

Cancer is a genetic disease that involves the accumulation of somatic mutations. Comprehensive understanding of the mutations that cause cancer and their functional effects is a critical step towards: a) global understanding of cancer development and tumor phenotypes, b) sub-classification of cancer based on mutational signatures, and c) developing targeted therapies based on mutations in specific ...
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 1

 TERMINÉ 

Axonuclear Communication in Neuronal Growth Control (NEUROGROWTH)

Date du début: 1 oct. 2013, Date de fin: 30 sept. 2018,

Neurons exhibit the most marked size differences and diversity in intrinsic growth rates of any class of cells. How then can a neuron coordinate between biosynthesis rates in the soma and the growth needs of different lengths of axons? The central hypothesis of this proposal is that neurons sense the lengths of the axonal microtubule cytoskeleton on an ongoing basis by bidirectional motor-dependen ...
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 1

 TERMINÉ 

Chiral Induced Spin Selectivity (CISS)

Date du début: 1 oct. 2013, Date de fin: 30 sept. 2018,

The overall objective is to fully understand the Chiral Induced Spin Selectivity (CISS) effect, which was discovered recently. It was found that the transmission or conduction of electrons through chiral molecules is spin dependent. The CISS effect is a change in the pradigm that assumed that any spin manipulation requiers magnetic materials or materials with high spin-orbit coupling. These unexp ...
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 1

 TERMINÉ 

Tracking Glycosylations with Targeted, Molecule-Sized “Noses” (GLYCOTRACKER)

Date du début: 1 oct. 2013, Date de fin: 30 sept. 2018,

Glycobiology is poised to be the next revolution in biology and medicine; however, technical difficulties in detecting and characterizing glycans prevent many biologists from entering this field, thus hampering new discoveries and innovations. Herein, we propose developing a conceptually novel technology that will allow straightforward identification of specific glycosylation patterns in biofluids ...
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 1

 TERMINÉ 

Synthetic Confined Environments as Tools for Manipulating Chemical Reactivities and Preparing New Nanostructures (CONFINEDCHEM)

Date du début: 1 oct. 2013, Date de fin: 30 sept. 2018,

"Nature has long inspired chemists with its abilities to stabilize ephemeral chemical species, to perform chemical reactions with unprecedented rates and selectivities, and to synthesize complex molecules and fascinating inorganic nanostructures. What natural systems consistently exploit - which is yet fundamentally different from how chemists perform reactions - is their aspect of nanoscale confi ...
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 1

 TERMINÉ 

Assessing the Effects of Rising O2 on Biogeochemical Cycles: Integrated Laboratory Experiments and Numerical Simulations (AEROBIC)

Date du début: 1 sept. 2013, Date de fin: 31 août 2018,

The rise of atmospheric O2 ~2,500 million years ago is one of the most profound transitions in Earth's history. Yet, despite its central role in shaping Earth's surface environment, the cause for the rise of O2 remains poorly understood. Tight coupling between the O2 cycle and the biogeochemical cycles of redox-active elements, such as C, Fe and S, implies radical changes in these cycles before, d ...
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 1

 TERMINÉ 

Multidimensional Spectroscopy at the Attosecond frontier (MIDAS)

Date du début: 1 sept. 2013, Date de fin: 31 août 2018,

The invention of multidimensional spectroscopy was a major leap in nuclear magnetic resonance. Comparable schemes in the optical regime have led to significant advances in our understanding of ultrafast dynamics in complex molecular systems. Currently, these multidimensional approaches are the most powerful and complete measurement schemes for resolving molecular dynamics on femtosecond time scale ...
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 2

 TERMINÉ 

Computational design of novel protein function in antibodies (ABDESIGN)

Date du début: 1 sept. 2013, Date de fin: 31 août 2018,

We propose to elucidate the structural design principles of naturally occurring antibody complementarity-determining regions (CDRs) and to computationally design novel antibody functions. Antibodies represent the most versatile known system for molecular recognition. Research has yielded many insights into antibody design principles and promising biotechnological and pharmaceutical applications. S ...
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 1

 TERMINÉ 

Exact Results in Quantum Field Theory (EXQFT)

Date du début: 1 sept. 2013, Date de fin: 31 août 2018,

Quantum field theory (QFT) is a unified conceptual and mathematical framework that encompasses a veritable cornucopia of physical phenomena, including phase transitions, condensed matter systems, elementary particle physics, and (via the holographic principle) quantum gravity. QFT has become the standard language of modern theoretical physics.Despite the fact that QFT is omnipresent in physics, we ...
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 1

 TERMINÉ 

Time and experience dependent evolution of hippocampal memory codes (MemoryCodes)

Date du début: 1 juin 2014, Date de fin: 31 mai 2018,

Following initial learning, information stored in memory undergoes a time- and experience-dependent evolution. Currently, the nature of this evolution at the neuronal ensemble level remains largely unknown. To obtain insight into this dynamic process there is a need to follow memory-associated neuronal representations in large populations of single cells over long periods of time. However, until r ...
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 1

 TERMINÉ 

Synthetic Biology Approach to Adhesion-Mediated Environmental Sensing (SYNAD)

Date du début: 1 mai 2012, Date de fin: 30 avr. 2018,

The primary aims of this work are tightly connected: (i) development of a bio-inspired “synthetic cell” capable of self-assembling, self-propelling and environmental sensing prepared with reduced molecular complexity compared to living cells (ii) quantitative assessment of the bio-activity of specific cellular components within these “synthetic cells”, leading to better fundamental understanding o ...
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 2

 TERMINÉ 

The translational landscape of virally infected cells (Host Translation)

Date du début: 1 mars 2014, Date de fin: 28 févr. 2018,

Viruses are completely reliant on the host cell machinery and have evolved many mechanisms to hijack it for their propagation. At the same time our cells have developed defense mechanisms to cope with infections. A key way by which viruses influence host physiology is through interaction with the cellular translation machinery. Not only viruses must co-opt this machinery to translate their own mRN ...
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 1

 TERMINÉ 

Identifying genes and pathways that drive molecular switches and back-up mechanisms between apoptosis and autophagy (DEATHSWITCHING)

Date du début: 1 mars 2013, Date de fin: 28 févr. 2018,

A cell’s decision to die is governed by multiple input signals received from a complex network of programmed cell death (PCD) pathways, including apoptosis and programmed necrosis. Additionally, under some conditions, autophagy, whose function is mainly pro-survival, may act as a back-up death pathway. We propose to apply new approaches to study the molecular basis of two important questions that ...
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 1

 TERMINÉ 

Transformation optics: cloaking, perfect imaging and horizons (TRANSFORM OPTICS)

Date du début: 1 mars 2013, Date de fin: 28 févr. 2018,

Transformation optics grew out of ideas for invisibility cloaking devices and exploits connections between electromagnetism in media and in geometries. Invisibility has turned from fiction into science since 2006, but is far from being practical yet. Advances in the theory of transformation optical are the key for bringing invisibility closer to practicality. Probably the most important practical ...
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 2

 TERMINÉ 

Novel Insights into Multi-drug Resistance to Antibiotics and the Primordial Ribosome (NOVRIB)

Date du début: 1 févr. 2013, Date de fin: 31 janv. 2018,

Multi-drug resistant phenotype formation creates global severe clinical threat among the most important challenges facing medicine today, dictating an urgent need for novel approaches. We aim to reveal the scope and mechanisms of resistance in pathogens, by studies that have not been pursued so far worldwide. In parallel we initiated innovative research towards understanding the ribosome origin, a ...
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 1

 TERMINÉ 

Learning to read the code of large neural populations (NEURO-POPCODE)

Date du début: 1 janv. 2013, Date de fin: 31 déc. 2017,

Information is represented and transmitted in the brain by the joint activity of large groups of neurons. Understanding how information is “written” in these population patterns, and how it is read and processed, is a fundamental question in neuroscience. Yet, because of the huge number of potential activity patterns and complexity of natural stimuli, most of our understanding of the code relies o ...
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 1

 TERMINÉ 

The mechanisms that underlie the development of a tendon-bone attachment unit (TENDONTOBONE)

Date du début: 1 janv. 2013, Date de fin: 31 déc. 2017,

We walk, run and jump using the complex and ingenious musculoskeletal system. It is therefore puzzling that although each of its components has been extensively studied, research of the musculoskeleton as an integrated system and, in particular, of its assembly has been scarce. In recent years, studies conducted in my lab have demonstrated the centrality of cross regulation between musculoskeletal ...
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 1

 TERMINÉ 

Frontiers of Oxidative Protein Folding and Assembly: Catalysis of Disulfide Formation Downstream of the Endoplasmic Reticulum (QSOX1BIOFUNC)

Date du début: 1 déc. 2012, Date de fin: 30 nov. 2017,

Quiescin sulfhydryl oxidase (QSOX), which catalyzes disulfide cross-linking in proteins, is up-regulated in many tumor types. QSOX is the only disulfide catalyst to undergo regulated secretion from cells, but the biological role of the enzyme, its substrates, and its mechanistic link to cancer are obscure. In addition to determining the first X-ray crystal structures of QSOXs, we recently discover ...
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 1

 TERMINÉ 

Evolutionary mechanisms of epigenomic and chromosomal aberrations in cancer (EVOEPIC)

Date du début: 1 déc. 2012, Date de fin: 30 nov. 2017,

Our working hypothesis is that tumorigenesis is an evolutionary process that fundamentally couples few major driving events (point mutations, rearrangements) with a complex flux of minor aberrations, many of which are epigenetic. We believe that these minor events are critical factors in the emergence of the cancer phenotype, and that understanding them is essential to the characterization of the ...
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 TERMINÉ 

Exploiting homomers to reveal new principles of protein interaction, polymerization and aggregation (Homomers)

Date du début: 1 déc. 2013, Date de fin: 30 nov. 2017,

In the protein universe, 30 to 50% of proteins self-assemble to form symmetrical complexes consisting of multiple copies of themselves, called homomers. A peculiarity of homomers is that any mutation is necessarily repeated in all subunits. In a symmetric dimer for example, any mutation of one copy is also found in the second identical copy. Depending where the mutation occurs on the surface, the ...
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 TERMINÉ 

Uncovering metabolic cycles in mammals and dissecting their interplay with circadian clocks (METACYCLES)

Date du début: 1 nov. 2012, Date de fin: 31 oct. 2017,

The physiology and behavior of mammals are subject to daily oscillations that are driven by an endogenous circadian clock. The mammalian circadian timing system is composed of a central pacemaker in the brain that is entrained by daily light-dark cycles and in turn synchronizes subsidiary oscillators in virtually all cells of the body. The core clock molecular circuitry is based on interlocked neg ...
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 TERMINÉ 

The Role of Elimination of Senescent Cells in Cancer Development (ELIMINATESENESCENT)

Date du début: 1 nov. 2012, Date de fin: 31 oct. 2017,

Cellular senescence, which is a terminal cell cycle arrest, is a potent tumor suppressor mechanism that limits cancer initiation and progression; it also limits tissue damage response. While senescence is protective in the cell autonomous manner, senescent cells secrete a variety of factors that lead to inflammation, tissue destruction and promote tumorigenesis and metastasis in the sites of their ...
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