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

    Kondrashov, Fyodor (CRG)

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    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)

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    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)

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    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

  • Chimpanzee and Bonobo ancient hybridization  (2016)

    Marquès Bonet, Tomàs (UPF)

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    Chimpanzee and Bonobo ancient hybridization 

    This year, a study published in Science and led by Tomàs Marquès-Bonet, ICREA researcher at the Institute of Evolutionary Biology (IBE), and the Centro Nacional de Analisis Genomico (CNAG-CRG) revealed novel ancient admixture events among the extant species closest to humans: bonobos and chimpanzees. This study has been then the first study to reveal admixture among the species similar to what has been reported between humans and Neanderthals and shows that admixture might have been a common occurrence during human and primate evolution.

    Between 1,5 and 2 million years ago chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) split from a common ancestor and evolved important strong physical and behavioural differences. To this day, the existence of gene flow between the species has not been considered due to the Congo River that physically separates the geographical distribution ranges of the species. The studied samples, comprising 75 complete genomes of chimpanzees and bonobos sequenced at the CNAG-CRG, cover 10 countries in Africa, from the westernmost to the easternmost region of the chimpanzee range. The results have direct application to the conservation of these species because they permit the detection of the origin of chimpanzees confiscated from illegal trafficking. The researchers have found that central and eastern chimpanzees share significantly more genetic material with bonobos than other chimpanzee subspecies do. Thus, it is believed that the admixture between bonobos and chimpanzees occurred during two different episodes: the first one, less than 500,000 years ago and the second one more recently, less than 200,000 years ago.

    Compared to our knowledge of the origins and population history of humans, much less is known about the extant species closest to humans, and since many predictions suggest the disappearance of chimpanzees and bonobos within the twenty-first century, this is one of the current efforts to pull together all forces in order to understand and protect the chimpanzees and bonobos before they disappear.

  • A mutation that alters the routes of HIV spread in the body (2016)

    Martínez-Picado, Javier (IrsiCaixa)

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    A mutation that alters the routes of HIV spread in the body

    Siglec-1 is a protein that plays a key role in HIV spread in the body that our group identified four years ago, in an article published in PLoS Biology. This protein is the receptor responsible for trans-infection of HIV (the AIDS virus) to CD4 T lymphocytes. Trans-infection occurs when the virus penetrates into a family of immune cells, called myeloid cells, which are supposed to activate the immune response. HIV uses Siglec-1 to penetrate these cells and turn them into "Trojan horses", as the virus prevents them to initiate an adequate immune response and uses them to reach its main target, the CD4 T lymphocytes.

    We have described now in Nature Communications the existence of a genetic variant that prevents the production of Siglec-1. This is a very rare mutation: it is estimated that only 1.3% of the European population has it in at least one allele, and approx 0.05% has it in the two alleles. Despite this low frequency, and after a screening of more than 4,000 people infected with HIV, our study identified for the first time that there are patients who naturally lack this pathway of viral spread: 97 people in the study had the mutation in one of their two alleles, and two had it in both.

    After studying the effect of this alteration in cells taken from patients, we found that the mutation reduces the ability of myeloid cells to capture the virus and transfer it to CD4 T lymphocytes. We observed that Siglec-1 is expressed to a greater extent in people who do not have the mutation, to a lesser extent in those who only have one copy with the mutation, and absolutely nothing in those who have it in both copies. Therefore, the absence of the receptor in people who have the mutation in their two gene copies prevents HIV from entering the myeloid cells and infecting the CD4 T lymphocytes.

    Since the absence of this protein does not seem to have any other effect in people affected by the mutation, these results suggest that it would be feasible to develop drugs, complementary to the current ones, intended to block the function of Siglec-1.

  • Simple patterning of graphene oxide with interest to build electronic devices and biosensors (2016)

    Merkoçi, Arben (ICN2)

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    Simple patterning of graphene oxide with interest to build electronic devices and biosensors

    Fast prototyping of electronic devices including biosensors is of great importance to reach the demand for cost/efficient technologies with interest for industries including “Maker” or “Do It Yourself” communities. Between various nanomaterials, graphene is emerging as a very interesting alternative building block for such devices given advantageous optical and electronic properties beside robustness, low cost and easy to obtain procedures. In this context we developed a simple and versatile graphene oxide printing technology using wax printed membranes for the fast patterning and water activation transfer through pressure- based mechanisms. The wax printed membranes have 50 μm resolution, longtime stability and infinite shaping capability. The use of these membranes complemented with the vacuum filtration of graphene oxide provides the control over the thickness. Our demonstration provides a solvent free methodology for printing graphene oxide devices in all shapes and all substrates using the roll-to-roll automatized mechanism present in the wax printing machine. Graphene oxide was transferred over a wide variety of substrates as textile or plastics in between others. Our patented technology (https://www.google.com/patents/WO2015193486A1?cl=en) on graphene patterning is already in use by Biolin Scientific (Sweden) who already launched the first graphene-based sensors with interest for biosensing applications (http://www.biolinscientific.com/product/q-sense-sensors/). Based on our patented technology (graphene patterning for electronic devices) a Spin Off company (GraphenicaLab) is already created.