Highlights

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  the most outstanding publications of the year 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.

LIST OF SCIENTIFIC HIGHLIGHTS

Format: yyyy

  • The importance of location, where one amino acid makes the difference (2020)

    Serrano Pubul, Luis (CRG)

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    The importance of location, where one amino acid makes the difference

    The C-terminal sequence of a protein is involved in processes such as efficiency of translation termination and protein degradation. However, the general relationship between features of this C-terminal sequence and levels of protein expression remains unknown. Here, we identified C-terminal amino acid biases that are ubiquitous across the bacterial taxonomy (1582 genomes). We showed that the frequency is higher for positively charged amino acids (lysine, arginine) while hydrophobic amino acids and threonine are lower. We then studied the impact of C-terminal composition on protein levels in a library of M. pneumoniae mutants, covering all possible combinations of the two last codons. We found that charged and polar residues, in particular lysine, led to higher expression, while hydrophobic and aromatic residues led to lower expression, with a difference in protein levels up to 4-fold. We further showed that modulation of protein degradation rate could be one of the main mechanisms driving these differences. Our results demonstrate that the identity of the last amino acids has a strong influence on protein expression levels and therefore it is important to look at it in biotechnological applications.

  • The Brain’s Connectome: Why Layers at Different Scales Seem Strangely Similar (2020)

    Serrano, M. Ángeles (UB)

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    The Brain’s Connectome: Why Layers at Different Scales Seem Strangely Similar

    The architecture of the brain supports cognitive and behavioral functions and it is extremely complex with connections at multiple layers that interact with each other. However, research efforts are usually focused on a single spatial scale. In a study led by ICREA research professor M. Ángeles Serrano, researchers studied the multiscale spatial organization of the brain and observed that, in a geometric network model, the layers at different resolution are self-similar, that is, as we move away, the geometric and connectivity structure of the layers remains the same.

    In order to carry out this study, researchers used two high-quality datasets with networks of neural connections, connectomes, of eighty-four subjects with five anatomical resolutions for each that expand over a series of interrelated length scales. According to Prof. Serrano, "the self-similarity we determined as a pattern in the multiscale structure of the human connectome implies that brain connectivity at different scales is organized under the same principles, that lead to efficient decentralized communication". This means that underlying connectivity rules that explain the brain's connectome are independent from the observation scale and we do not need a specific set of rules for each scale.

    The model predicts observations through the application of a renormalization protocol that uses a hyperbolic network map of the human connectome, so that regions at short distances are more likely to be connected. This type of model enables researchers to explain the universal features of real networks and their multiscale structure. For every scale, there is a remarkable congruence between empirical observations and predictions provided by the model. The results show that the same rules explain the formation of short and long-range connections in the brain within the rank of length scales that cover the used datasets.

    The implications of this discovery are several. On the one hand, it can be useful in fundamental debates, such as whether the brain is working close to a critical spot. On the other hand, it can have applications for advanced tools on brain functioning simulation.

  • Revealing the peculiar magnetism of the frustrated “Cairo” pentagonal antiferromagnet (2020)

    Skumryev, Vassil (UAB)

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    Revealing the peculiar magnetism of the frustrated “Cairo” pentagonal antiferromagnet

    The pentagon, a five-sided polygon, is an old issue in mathematical recreation. It forms the faces of the dodecahedron, one of the platonic solids whose shape is reproduced in biological viruses and in clusters. Contrary to triangles, squares or hexagons, it is impossible to tile a plane with congruent regular pentagons; the tilings must involve additional shapes to fill the gaps - fig.1. There exist, however, several possibilities of tessellation with non-regular pentagons, a famous one being the Cairo tessellation whose name was given because it appears in the streets of Cairo.

    Using neutron diffraction, several years ago we found that the Fe magnetic moments of Bi2Fe4O9 at the two distinct crystallographic sites, Fe1 and Fe2, form a pattern, which constitutes the first materialization of pentagonal magnetic structure - fig.2. Because of its odd number of bonds per elemental brick, this so-called Cairo pentagonal lattice is prone to geometric frustrated magnetism arising when all pair interactions are not simultaneously satisfied. The peculiarity of this non-collinear structure arises from the complex connectivity of the pentagonal lattice, a novel feature compared to the well-known case of triangle-based lattices, opening new perspectives in the field of magnetic frustration. In this case, both the frustration and the complex connectivity are at play and there is no macroscopic degeneracy of the ground state. In a recent inelastic neutron scattering study [1], the magnetic interactions in the pentagonal lattice and their hierarchy were determined. It unveils various facets of unconventional magnetism, with distinct behaviors associated with the two inequivalent Fe sites of the pentagonal lattice. The Fe1 ions produce strongly coupled antiferromagnetic pairs of spins (dimers) separated by much less correlated Fe2 spins, dominating the correlated paramagnetic state (above the temperature of magnetic order).  Whereas in the ordered magnetic state, the pairs of Fe2 spins produce original spin dynamics, associated with protected local motions, coexisting with dispersive spin waves. This result should be very general in systems with similar lattice topology.

  • Higher-order multipolar interactions in insulating crystals (2020)

    Stengel, Massimiliano (CSIC - ICMAB)

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    Higher-order multipolar interactions in insulating crystals

    The theoretical foundation of lattice dynamics in crystalline insulators rests on the separation between short-range and long-range interatomic force constants (IFCs). The latter stem from the macroscopic electric fields that are associated with long-wavelength phonons. These, in turn, result in a nonanalytic behavior of the dynamical matrix near the Brillouin zone center, which manifests itself as a polynomial (rather than exponential) decay of the IFCs in real space.

    The leading long-range contribution, which has the form of a dipole-dipole interaction and decays as the inverse cube of the interatomic distance, has been known since the fifties. The work of Cochran and Cowley, and later Pick, Cohen and Martin, established the correct formula in the generic case of an anisotropic crystal, paving the way for modern first-principles implementations. The main physical consequence of the dipole-dipole interaction resides in the frequency splitting between longitudinal (LO) and transverse (TO) optical phonons near the Brillouin zone center. 

    The Cochran-Cowley formula is, however, only the leading term in a multipolar expansion of the charge response to atomic motion. Here we provide an exact generalization to higher multipolar orders, involving e.g. dipole-quadrupole interactions. We demonstrate that such generalization can be crucial in piezoelectric crystals, where the sound velocity is influenced by electrostatics. Neglect of dynamical quadrupoles often results in an erroneous description of the acoustic branches near the zone center, as we demonstrate with our calculations of rhombohedral BaTiO3. [1]

    The importance of quadrupoles is not limited to lattice dynamics. The long-range potentials produced by atomic motion are crucial for a correct description of electron-phonon couplings as well, which govern a wide range of physical properties (e.g., electron mobility). The counterpart of the Cochran-Cowley formula in this context consists in the Fröhlich model, which we have also generalized to the quadrupolar level. [2] This allows for a substantial improvement in the accuracy and efficiency of the calculations.

  • Mutations in cancer genomes: foggy with a chance of thunderstorms (2020)

    Supek, Fran (IRB Barcelona)

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    Mutations in cancer genomes: foggy with a chance of thunderstorms

    Local hypermutation is an unusual occurence of a cluster of nearby mutations that arose in a single event, which can severely damage genetic material. The best known type of local hypermutation, called a mutation shower or thunderstorm, can contain tens of closely spaced mutations. However, these spectacular mutational events occur only rarely. Nonetheless their existence suggests that other types of local hypermutation may be more widespread in genomes than previously appreciated.

    We have developed a sensitive statistical framework, HyperClust, to detect mutation clustering in cancer genomes. The application of HyperClust to thousands of cancer genome sequences revealed a new type of localized hypermutation pattern that we named mutation fog. This can generate hundreds of mutations per cell and can occur in different human somatic tissues. Such mutations are unevenly distributed across the human chromosomes: they preferentially accumulate in the most important, euchromatic regions of the genome, where gene density is higher.

    Surprisingly, this new hypermutation type is facilitated by a normal DNA repair process. When cells sense a mismatch in their DNA, they undergo a DNA repair reaction, in order to preserve genetic information. Remarkably, this reaction can become coupled with the APOBEC3A enzyme, which is normally used by human cells to defend against retrotransposons and viruses by damaging their nucleic acids. In some cases, when both the APOBEC enzyme and the DNA repair process are active at the same time, APOBEC is able to hijack the DNA repair process, generating the mutation fog.

    Such APOBEC mutagenesis has a high propensity to generate impactful mutations in oncogenes and tumor suppressor genes, which can exceed that of other common carcinogens such as tobacco smoke and ultraviolet radiation. Because human cells direct their DNA repair capacity towards more important genomic regions, carcinogens that subvert DNA repair can be remarkably potent.

  • Shedding light on the control of microtubule nucleation (2020)

    Surrey, Thomas (CRG)

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    Shedding light on the control of microtubule nucleation

    Microtubules are tube-like protein polymers that are essential for correct intracellular organization and for cell division. The number of microtubules needs to be precisely controlled and this is done by a protein complex that is thought to serve as a template for microtubule growth. We have developed a fluorescence microscopy-based assay allowing us to observe new microtubule formation from single templates. We found that the isolated templating complex is surprisingly inefficient in starting microtubule growth. Cryo-electron microsopy allowed then to obtain the structure of the complex at high resolution which revealed a mismatch between template and microtubule. This suggest that a shape change of the template is required to activate it and that in living cells template-binding proteins may induce this chance controlling the formation of new microtubules.

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