Every year, a committee of experts sits down with a tough job to do: from among all ICREA publications, they must find a handful that stand out from all the others. This is indeed a challenge. The debates are sometimes heated and always difficult but, in the end, a shortlist of 24 publications is produced. No prize is awarded, and the only additional acknowledge is the honour of being chosen and highlighted by ICREA. Each piece has something unique about it, whether it be a particularly elegant solution, the huge impact it has in the media or the sheer fascination it generates as a truly new idea. For whatever the reason, these are the best of the best and, as such, we are proud to share them here.


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  • Understanding the evolution of genomes and the regulation of the proteome. (2012)

    Ribas de Pouplana, Lluís (IRB Barcelona)

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    Understanding the evolution of genomes and the regulation of the proteome.

    We have discovered a new mechanism for protein synthesis control (Novoa et al., Cell 2012). More specifically, we have described the role of two tRNA anticodon modifications in genome evolution and proteome regulation across the complete tree of life. We have shown that these modifications contributed to the evolution of genomes, and currently play a part in the control of protein synthesis in extant species.

    We have demonstrated that the codon composition of highly expressed genes is enriched in triplets recognized by modified tRNAs. Thus, a new mechanism for the control of gene expression arises based on the relationship between the codon composition of any given gene and the existing pool of modified tRNAs in the cell. We want to explore this relationship and characterize how levels of modified tRNAs may affect gene expression levels. For that purpose we have chosen two experimental models that represent extreme cases either in the levels of modification activity or in the numbers of tRNA genes in the genome.

    More specificaly, we propose to study the biological significance of extreme variations in the levels of tRNAmodification that are reported between normal and transformed mammalian cells. On the other hand, we propose to study the biological role of these modifying enzymes in organisms that contain a dramatically simplified complement of tRNA genes. Specifically, we will be investigating their role in Plasmodium falciparum, the causing agent of malaria and the eukaryotic organisms with the simplest set of tRNA genes in its genome. Given the simplicity of tRNA gene composition, and the extreme codon usage bias of Plasmodium, we suspect that the function of tRNA modification is particularly important to allow a proper match between tRNA content and genetic codon composition.

  • Network structure of the plant circadian clock. (2012)

    Riechmann Fernández, Jose Luis (CRAG)

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    Network structure of the plant circadian clock.

    Molecular circadian clocks are ubiquitous endogenous mechanisms that allow organisms to temporally organize biological activities, coordinating them with the daily environmental cycle. In plants, the circadian clock regulates processes such as growth rate, primary and secondary metabolism, hormone biosynthesis and responses, stomatal opening, water stress responses, water uptake, leaf movement, petal opening, seed dormancy, and pathogen defense. In addition, the circadian clock forms the basis for one of the genetic pathways that control the timing of the transition from vegetative to reproductive growth, or flowering.

    In an article published in Science -a collaboration with the group of CSIC Professor Paloma Mas, also at CRAG- we describe our efforts to understand the molecular mechanisms underlying the function of TIMING OF CAB EXPRESSION1 (TOC1). In many organisms, the circadian clock is composed of functionally coupled morning and evening oscillators. In Arabidopsis, oscillator coupling relies on a core loop in which the evening oscillator component TOC1 was proposed to activate a subset of morning-expressed oscillator genes. We showed that TOC1 does not function as an activator but as a general repressor of oscillator gene expression. Repression occurs through TOC1 rhythmic association to the promoters of all oscillator genes. Hormone-dependent induction of TOC1 and analysis of RNAi plants showed that TOC1 prevents the activation of morning-expressed genes at night. Thus, the morning and evening oscillator loops are connected through the repressing activity of TOC1.

    These results overturn the canonical, long-standing model of the plant circadian clock, in which TOC1 was presumed to be an activator of a reduced number of oscillator genes, not a general repressor of oscillator gene transcription, as has now been demonstrated.

  • Structural edge instabilities and Robustness of the Quantum Hall effect in Graphene : Mystery solved (2012)

    Roche, Stephan (ICN2)

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    Structural edge instabilities and Robustness of the Quantum Hall effect in Graphene : Mystery solved

    Together with some colleagues from the Graphene Research Center in Singapore, the ICMM-CSIC in Madrid and the IMEP-LAHC (Grenoble INP), we have proposed an explanation for an enigma in graphene: the fact that when using conventional methods of electric current detection with low to medium intensity applied magnetic fields (2 to 20 Tesla), scientists have repeatedly failed to observe the quantum Hall effect in graphene samples with scrolled edges (see Figure), known as graphene nanoscrolls. This issue was raised by Andre Geim, the 2011 Physics Nobel Laureate for the discovery of groundbreaking properties of this carbon-based two-dimensional material with exceptional physical properties.

    In the quantum Hall effect, a fundamental mesoscopic quantum phenomenon in 2D materials, the application of an external magnetic field forces the electric charges in the sample to segregate outwards to the sample´s edges (referred as chiral edge states), much like a referee forcing the players of two brawling football teams to separate onto either side of the pitch. This establishes a quantized Hall conductance together with a vanishing longitudinal conductivity.

    When researchers study the quantum behaviour of electronic excitations in graphene (and other materials), they typically create a simple circuit in which current travels from a source contact at one end (or edge) of the material to a drain contact at the opposing end (or edge). This technique gives clear readings of the quantum Hall effect in completely flat graphene (such as samples that are bound to a substrate); in contrast, in free-standing graphene (see Figure (b)), which generally shows scrolled edges, the effect seems to be quenched.

    By measuring the magnetic field along the length and depth of the scrolled edges as well as in the flat portion of graphene samples of this type, we have deduced that these edges basically short circuit the very drains used to measure current in these types of experiment, jeopardizing the formation of chiral current generation at the edges. Non-chiral edges current propagate inside the scrolls whereas chiral currents are formed deeper inside the bulk, hence more sensitive to disorder and scattering. Accordingly, the observation of the Quantum Hall regime in suspended graphene is prohibited in presence of such structural edge instabilities.

  • Ultracold Atoms in Optical Lattices Simulating quantum many-body systems By Maciej Lewenstein, Anna Sanpera and Verónica Ahufinger (2012)

    Sanpera Trigueros, Anna (UAB)

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    Ultracold Atoms in Optical Lattices
    Simulating quantum many-body systems
    By Maciej Lewenstein, Anna Sanpera and Verónica Ahufinger

    First comprehensive book on ultracold gases in optical lattices
    First book on quantum simulators
    Broad range of topics covered
    Interdisciplinary character
    Covers both theoretical and experimental aspects

    Quantum computers, though not yet available on the market, will revolutionize the future of information processing. Quantum computers for special purposes like quantum simulators are already within reach. The physics of ultracold atoms, ions and molecules offer unprecedented possibilities of control of quantum many body systems and novel possibilities of applications to quantum information processing and quantum metrology. Particularly fascinating is the possibility of using ultracold atoms in lattices to simulate condensed matter or even high energy physics.

    This book provides a complete and comprehensive overview of ultracold lattice gases as quantum simulators. It opens up an interdisciplinary field involving atomic, molecular and optical physics, quantum optics, quantum information, condensed matter and high energy physics. The book includes some introductory chapters on basic concepts and methods, and then focuses on the physics of spinor, dipolar, disordered, and frustrated lattice gases. It reviews in detail the physics of artificial lattice gauge fields with ultracold gases. The last part of the book covers simulators of quantum computers. After a brief course in quantum information theory, the implementations of quantum computation with ultracold gases are discussed, as well as our current understanding of condensed matter from a quantum information perspective.

    Readership: Graduate students and researchers in atomic, molecular, and optical physics, quantum optics, quantum information, condensed matter physics, and quantum field theory.

  • USP15: a Promising Novel Therapeutic Target in Cancer (2012)

    Seoane Suárez, Joan (VHIO)

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    USP15: a Promising Novel Therapeutic Target in Cancer

    In March 2012, Dr. Joan Seoane´s group at the Vall d'Hebron Institute of Oncology (VHIO) published a study in Nature Medicine identifying USP15 as a critical protein in cancer that, thanks to its molecular characteristics, shows enormous therapeutic promise.

    USP15 as a "Biological Thermostat" at the core of a TGFß chain reaction, Dr. Seoane's team unmasked the USP15 enzyme as the activator of the TGFß chain reaction. In normal tissue, USP15 acts by controlling and correcting the TGFß activity in the same way that a thermostat regulates temperature. If the TGFß activity is high, USP15 reduces; and if it is low, USP15 increases the TGFß activity. USP15 therefore achieves optimal TGFß activity.

    Protein stability is regulated through the elimination or aggregation of ubiquitins, small proteins that establish which molecules need to be eliminated. This process is regulated by deubiquitinating enzymes (DUBs) and ubiquitin ligases such as USP15 and Smurf2, respectively, which determine the correct level of a protein under certain physiological conditions. The group found that in this orchestrated manner USP15 controls and adapts the TGFß receptor stability and, therefore, the activity of the pathway.

    The problem arises when, in some tumors, the USP15 gene is amplified due to genetic mutations and the enzyme is overproduced. The thermostat breaks down and is therefore only sensing the "cold" resulting in the (overheating) overactivation of the TGFß pathway. In this context, TGFß acts as an oncogenic factor promoting tumor progression. Hence, the amplification of the USP15 gene promotes tumorigenesis through the hyperactivation of the TGFß signal.

    USP15 as a therapeutic target in cancer Seoane's lab used a model of human glioblastoma that reproduces in mice the tumor from patients undergoing surgery at the Vall d'Hebron Hospital. Inactivation of USP15 resulted in a decrease in oncogenesis indicating that USP15 is a critical oncogenic factor in tumors with USP15 gene amplification. This opens a novel avenue of therapeutic strategies against such a dismal disease. Since USP15 is an enzyme, small organic molecules have been designed to inhibit its catalytic activity being putative therapeutic compounds. The group has proved the efficacy of these USP15 inhibitors in preclinical models of glioblastoma with promising results.

    Remarkably, USP15 is not only an oncogenic factor in glioblastomas since the USP15 gene amplification has also been found activated in other types of cancer such as breast or ovarian cancer

  • Phonons in slow motion (2012)

    Sotomayor Torres, Clivia Marfa (ICN2)

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    Phonons in slow motion

    A main issue in information technology affecting heterogeneous integration and autonomous systems is the fact that they need advanced thermal management and, in the autonomous case, their own energy source (energy harvesters). In general, in energy conservation and generation and in efficient energy transformation, among others, the control of heat dissipation is of paramount importance. From data centres to basic transistors with a sub 20 nm gate width, the issue is thermal management involving heat transport in the plane and across interfaces, all of which is exacerbated as dimensions become smaller.
    Our work addresses the physics underpinning heat transport by focusing on the changes in the dispersion relations of phonons in freestanding membranes down to 8 nm thickness. We have observed and simulated the strong modifications of the dispersion of phonons in model structures, namely freestanding ultra-thin crystalline silicon membranes, which happen to be the materials at the centre of information and communication technologies.
    Our results show that to simulate, and eventually design, new components and circuits, thermal conductance/conductivity and other properties affected by the density of states, including the spectral and geometric dependencies of phonon properties, must be taken into account. Although our studies are only on Si, they are equally applicable to other thin film materials and nanostructures and even more so to multilayer structures, since the acoustic impedance and contrast changes with type, shape, geometry and thickness of each layer.
    This is probably the first report of Lamb waves in the sub-THz regime, which will be of interest to the acoustics community and some sectors of mechanical engineering.
    Our results impact directly not only heat dissipation issues in nanoelectronics but also the physics of nano-scale thermoelectricity. Both are phonon-dependent and naturally affected by temperature and frequency.
    All sensors using nanostructures which require low power electronics and energy harvesting to be really "autonomous", sooner or later, hit upon the issue of thermal management. Our results will help in the modelling and design of nanotechnology-enabled sensors, especially to advance knowledge on lattice vibrations and heat transport in nanosystems.
    The simulations, theories and experiments are intricate and involved knowledge from mechanical and electrical engineering, solid state physics, statistical mechanics, inorganic chemistry and even biophysics. For example, artificial