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

  • Vision restoration by molecular prostheses (2016)

    Gorostiza Langa, Pau (IBEC)

    view details
    CLOSE

    Vision restoration by molecular prostheses

    A new class of light-regulated drug, targeted covalent photoswitches (TCPs) have been developed at IBEC together with collaborators at CID, ICIQ, INA, IRB Barcelona, CIBER-BBN and the Miguel Hernández and Alcalá de Henares universities. TCPs act as prosthetic molecules that can restore photoresponses in degenerated retinas and may help restore vision in cases of retinal degeneration.

    Light-regulated drugs like the ones developed in recent years at IBEC can be photoswitched remotely – that is to say, their biological activity can be turned on and off using light. Now, researchers have targeted proteins from the neurons involved in vision, which are not affected by the degenerative processes that destroy photoreceptor cells. Under normal conditions, the photoreceptor cells of the eye – the rods and cones – are those that react to receive light and activate, in turn, other retinal cells. The designed molecules isomerize with light and activate the surviving neuronal receptors involved in sending visual signals to the brain, thus replacing to some extent the functional role of the photoreceptors.

    Until now, the type of molecules that can be photoswitched in endogenous receptors – those found naturally in the organism – have been photochromic ligands, freely diffusible small molecules that act directly on these proteins. But they often display low specificity for their target, their remote control is limited to a narrow concentration range, and they are rendered less efficient by dilution in tissue. To avoid these drawbacks, photocontrol of these molecules can be confined to particular receptors; but this comes at the cost of genetic manipulation, which poses other limitations. To overcome these problems, the researchers developed a new chemical strategy to photoswitch protein activity that has the advantages of attachment to the target, but can be applied to endogenous proteins without requiring genetic manipulation. These TCPs might work in a variety of organisms, including human, for which limited (opto)genetic manipulation techniques are currently available. This prospect makes the results on retina photosensitization especially appealing.

     

  • A better, faster recommendation algorithm (2016)

    Guimerà Manrique, Roger (URV)

    view details
    CLOSE

    A better, faster recommendation algorithm

    The internet is rife with recommendation systems, suggesting movies you should watch or people you should date. These systems are tuned to match people with items, based on the assumption that similar people buy similar things and have similar preferences. In other words, an algorithm predicts which items you will like based only on your, and the item’s, previous ratings.

    But many existing approaches to making recommendations are simplistic. Mathematically, these methods often assume people belong to single groups, and that each one group of people prefers a single group of items. For example, an algorithm might suggest a science fiction movie to someone who had previously enjoyed another different science fiction movie—even if the movies have nothing else in common.

    In a new paper in the Proceedings of the National Academy of Sciences, Guimerà and his collaborators introduce a new recommendation system that differs from existing models in two major ways. First, it allows individuals and items to belong to mixtures of multiple groups. Second, it doesn't assume that ratings are a simple function of similarity; instead, it predicts probability distributions of ratings based on the groups to which the person or item belongs. This flexibility makes the new model more realistic than existing models that posit a linear relationship between users and items. Not everyone uses ratings in the same way—if a person rates a movie 5 instead of 1, that doesn’t mean she likes it five times as much. The new model can learn these nonlinear relationships between users and ratings.

    Guimerà and his collaborators tested their model on five large datasets, including recommendations systems for songs, movies, and romantic partners. In each case, the new model’s predicted ratings proved more accurate than those from existing systems, sometimes even doubling the their accuracy—and their algorithm is faster than competing methods as well.

  • A Large Universe dominated by dark energy might be the most hospitable to harbouring complex life (2016)

    Jiménez Tellado, Raúl (UB)
    Verde, Licia (UB)

    view details
    CLOSE

    A Large Universe dominated by dark energy might be the most hospitable to harbouring complex life

    Gamma-ray bursts (GRBs) are copious sources of gamma rays whose interaction with a planetary atmosphere can pose a threat to complex life. Using recent determinations of their rate and probability of causing massive extinction, we explored in a recent Physical Review Letters  (PRL, 2016, 116, 1301) what types of universes are most likely to harbor advanced forms of life. Life survival to GRBs favors dark-energy-dominated universes. Within a cold dark matter model with a cosmological constant, the likelihood of life survival to GRBs is governed by the value of Λ and the age of the Universe. We find that we seem to live in a favorable point in this parameter space that minimizes the exposure to cosmic explosions, yet maximizes the number of main sequence (hydrogen-burning) stars around which advanced life forms can exist.

  • The Green Fluorescent Protein illuminates a fitness landscapes (2016)

    Kondrashov, Fyodor (CRG)

    view details
    CLOSE

    The Green Fluorescent Protein illuminates a fitness landscapes

    A central question in biology is how changes on the genotype level manifest themselves on the level of the phenotype. In other words, if a mutation occurs in a gene - what happens? A potent metaphor is the fitness landscape, an abstract representation of how genetic changes affect what happens to the organism. In this study, we selected the Green Fluorescent Protein (GFP), which normally fluoresces in green, as a model to study the question of how mutations would affect its function of fluorescent. 

    We created over 50,000 thousand genotypes of GFP proteins with different number of mutations and individually accessed their levels of fluorescence. We found that mutations do not contribute independently to GFP fluorescence. The main mechanism is best described as the poor get poorer, with a genotype carrying several mutations showing a level of fluorescence much lower than would be expected if those mutations were making their contribution independently of each other. The results of our study present a model for the prediction of how multiple mutations can collectively affect the function of a protein. Perhaps similar studies can illuminate the mechanism of collective action of mutation on more complex genotypes.

  • Spin glass physics with trapped ions (2016)

    Lewenstein, Maciej Andrzej (ICFO)

    view details
    CLOSE

    Spin glass physics with trapped ions

    One of the most striking discoveries of quantum information theory is the existence of problems that can be solved in a more efficient way with quantum resources than with any known classical algorithm.

    Number-partitioning, which refers to the simple task of dividing a set of numbers into two groups of equal sums is, in fact, a very difficult problem to solve with classical computers.

    Often, such problems can be related to a physical model, which then allows for solving the problem by finding the minimum energy state of the model. Here, an important role is played by spin glass models, that is, models describing a collection of tiny magnets interacting with each other in a random fashion.

    In the recent work published in Nature Communications, Dr. Tobias Grass, David Raventos, Dr. Christian Gogolin, led by ICREA Prof. at ICFO Dr. Maciej Lewenstein, in collaboration with Dr. Bruno Julia-Di­az from the University of Barcelona (UB), lay the theoretical foundations for a quantum simulation of spin glass physics with trapped ions.

    The idea proposed by the team of researchers shows how to tackle the problem of number partitioning by applying a strategy known as "quantum annealing". This is done by initially applying a strong magnetic field which is then switched off slowly during the simulation. In this way, the quantum state is deformed until it matches with the desired solution. This can be faster than other methods to solve the problem.

    The implementation of this approach is possible with state-of-the-art techniques for trapping, cooling, and manipulating ions. As Dr. Grass clearly states, "In the past, we have seen quantum simulations which solve a problem from quantum physics. In our approach, the same techniques are used to solve a problem from computer science. The results of our study opens a new path and brings us a step closer to the development of a quantum computer."

  • Increased mutation rate in DNA regions bound by proteins (2016)

    López-Bigas, Núria (IRB Barcelona)

    view details
    CLOSE

    Increased mutation rate in DNA regions bound by proteins

    Genetic mutations are changes in the DNA sequence that can cause errors in cell function, and in the worst case, their accumulation leads to serious diseases such as cancer. To avoid this, cells have mechanisms that are continuously detecting and repairing these changes, but which sometimes fail, resulting in the accumulation of mutations and the emergence of tumours. 

    The team of López-Bigas has shown that mutations accumulate at higher rate in regions of the DNA to which the so-called transcription factors, proteins that regulate the activity of different genes, are bound. The results of the study indicate that the binding of these proteins to the DNA hinders access to the DNA’s repair machinery, which ultimately causes the accumulation of genetic mutations in these areas. Specifically, the analysis of the genomes of 38 melanomas sequenced by The Cancer Genome Atlas Consortium shows that the mutation rate in these regions is approximately five times higher than in neighboring regions of the genome.

    Melanoma, one of the most aggressive types of skin cancer, has its origin on many occasions in DNA damage that ultraviolet (UV) rays cause in skin cells. This damage is repaired by a specific cellular mechanism called Nucleotide Excision Repair. The same mechanism is responsible for the repair of the damage caused by tobacco smoke and that lead to some types of lung cancer. For this reason, the researchers decided to test whether this phenomenon could also be observed in these other types of tumours. The results were reproduced, observing that the areas where transcription factors were bound in lung cells also had a much higher mutation rate than their neighboring regions of the genome. 

    The researchers also observed the mutation rate in melanomas show a periodicity, with higher mutation rate corresponding to nucleosome embeded DNA and lower in linker regions between nucleosomes.

    These findings have important implications for our understanding of mutational and DNA repair processes and for the identification of non-coding driver mutations

Pages