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 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.

LIST OF SCIENTIFIC HIGHLIGHTS

Format: yyyy
  • A new study on Ewing sarcoma will pave the way for personalized therapy for childhood cancer (2020)

    Di Croce, Luciano (CRG)

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    A new study on Ewing sarcoma will pave the way for personalized therapy for childhood cancer

    1% of all childhood cancers are Ewing tumors. It mainly affects children and adolescents, but is also seen in young adults, with males slightly more affected than females.

    Researchers at the Centre for Genomic Regulation (CRG) and the Institut de Recerca Sant Joan de Déu have found that the RING1B gene is critical for the development of Ewing sarcoma, a rare type of cancer that affects bones or the tissue around bones and it account for 1% of all childhood cancers. This newly uncovered epigenetic vulnerability in Ewing sarcoma cancer cells opens the opportunity for new therapeutic strategies.

    The new study published in Science Advances reports that RING1B and EWSR1-FLI1 localize at the same regions in the genome, where RING1B is responsible for EWSR1-FLI1 recruitment. EWSR1-FLI1 cannot activate its target genes and transform a cell without RING1B.

     

    Base on this common interested the Centre for Genomic Regulation (CRG) and the Institut de Recerca Sant Joan de Déu want to extend the investigation to brainstem glioma, which mainly affects children, and at the moment there is no treatment, and it has a poor prognosis.

    The tumor is made up of very different cells that vary from patient to patient, and even change during the course of the disease itself. This makes it difficult to find an effective treatment.

    Until now, research on this tumor has been based on studies at the individualized cell level. Instead, the project cooridnated by Dr Luciano Di Croce in collaboration with Dr Mora (HSJD) and Dr. Marti-Renom (ICREA), and sponsored by la Caixa proposes multicellular reconstruction of the tumor in 3D, using personalized models of the patient in mice (PDX-patient derived xenograft). These models will allow testing individualized treatments for this type of cancer.

     

  • A cancer mystery of more than forty years ago is solved thanks to Epigenetics (2020)

    Esteller Badosa, Manel (IJC)

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    A cancer mystery of more than forty years ago is solved thanks to Epigenetics

    Before the first oncogene mutations were discovered in human cancer in the early 1980s, the 1970s provided the first data suggesting alterations in the genetic material of tumors. In this context, the prestigious magazine "Nature" published in 1975 the existence of a specific alteration in the transformed cell: an RNA responsible for carrying an amino acid to build proteins (transfer RNA) was missing a piece, the enigmatic nucleotide "Y". After that outstanding observation, the most absolute silence and ignorance has reigned for forty-five years on the causes and consequences of not having that correct base in that RNA. The article published in the Proceedings of the National Academy of Sciences (PNAS) by the group of Dr. Manel Esteller solves this mystery by describing that in cancer cells the protein that generates the nucleotide "Y" is epigenetically inactivated, causing small but highly aggressive tumors.

    Since the original discovery in 1975, there has been much biochemical work to characterize the enzymes involved in the different steps that lead to the desired nucleotide "Y", a hypermodified guanine, but without connecting this characterization with its defect in tumor biology. Dr Esteller’s work have built the bridge between these two worlds by demonstrating that the epigenetic silencing of the TYW2 gene is the cause of the loss of the elusive nucleotide "Y". Epigenetic blockade TYW2 gene occurs mainly in colon, stomach and uterine cancer. And it has undesirable consequences for healthy cells: the postman (RNA) that sends the signal to produce the bricks of our body (proteins) begins to accumulate errors and the cell takes on a different appearance, far from the normal epithelium, which we call mesenchymal and which it is associated with the appearance of metastasis. In this regard, when we study patients with colon cancer in early stages, the epigenetic defect of TYW2 and the loss of the nucleotide "Y" is associated with those tumors that, although small in size, already lead to less survival of the person.

  • The Talmud in the Christian World: A New Approach to Christian-Jewish Relations During the Middle Ages (2020)

    Fidora Riera, Alexander (UAB)

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    The Talmud in the Christian World: A New Approach to Christian-Jewish Relations During the Middle Ages

    Invited to speak at the honorary lecture series of the Albertus-Magnus-Institut in 2019, A. Fidora has now published a pioneering monograph in the prestigious Lectio Albertina-series which presents essential results of his ERC-project on "The Latin Talmud". This reappraisal of the history of the Jewish people in thirteenth-century Europe is a major contribution to historical and social justice. At the same time, exploring the historical interactions between Christians and Jews is crucial for understanding Europe’s cultural and political identity, which was shaped not only by Christianity, but also by Judaism and Islam. This study brings to light the historical foundations of religious (in)tolerance, and underscores the necessity of protecting religious and cultural diversity in Europe.

     

  • How to be an animal? Evolution of the gene repertoire across the animal tree of life      (2020)

    Gabaldón Estevan, Toni (BSC-CNS)

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    How to be an animal? Evolution of the gene repertoire across the animal tree of life     

    How to be an animal? This was the ambitious question we had in mind when we started our project. It is well-known that many animal genes have a very old origin and that they originated before the split of animals and fungi. Then, if we share these ancient genes with fungi, what makes an animal an animal? How did animals acquired their intrincated morphology, illustrated by their brains, guts or gonads? To answer this, we decided to use a bioinformatic spyglass to carefully examine more than 230 animal genomes to shed light on how their genes had evolved. And since animals are so different, we decided to have a look at the gene repertoire of all main animal lineages, called phyla - the equivalent of playing Pokemon and catching them all. Previous studies had shown that, indeed, no single gene family characterizes the origin of animals. These studies analyzed similarities between animals and relatives from the static perspective of gene composition - what genes families are in their genomes -, but lacked the dynamics that evolutionary processes have, such as gene duplications or losses. Imagine that you want to prepare cookies. If you think about the ingredientes - flour, butter, milk, sugar and eggs - they are the same ones that you need to prepare pancakes. However, the amount of each ingredient, the order in which you add them and how - mix the butter with the milk and the sugar, then add the egg, after that add half of the flour and stir together, then slowly add more flour while homogenizing the dough - is completely different. The previous studies had discovered that the “ingredients” (or genes) to be an animal or a choanoflagellate are virtually the same. Using phylogenomics, we found that gene duplication was much higher in animals than in their relatives. We found two main waves of gene duplications in animals: one at their origin, and one at the level of phylum. Remarkably, the putative function of many of the duplicated genes at different evolutionary times was related to the neural system, highlighting the complex evolutionary plasticity of this system and potentially its convergent evolution across animals.

  • DECODING ASTROCYTES (2020)

    Galea, Elena (UAB)

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    DECODING ASTROCYTES

    Astrocytes are cells of the central nervous system (CNS). Although astrocytes are less popular than neurons, it is worth emphasizing that they are an integral part of neuronal circuits. According to the prevalent view, neurons are the CNS cells that carry the complex computations subserving coding, complex behaviors, and higher brain functions. In this perspective article we ask whether, beyond providing metabolic and homeostatic support to neurons, astrocytes are fundamental to CNS coding. If they do, specific questions are whether there are niche(s) in CNS coding that would particularly profit from astrocyte idiosyncrasies, and whether the impressive techniques and theoretical armamentarium deployed for neurons could be used—and are sufficient—to unravel possible astrocyte-based coding. Pioneering theoreticians in neuroscience argued that anatomical features provide valuable insights about how the CNS operates because ‘the nervous system is a product of evolution, not design. The computational solutions evolved by nature may be unlike those that humans would invent, if only because evolutionary changes are always made within the context of a design and architecture that already is in place’. Thus, we reason that the unique anatomical arrangement between astrocytes and neurons might be part of computational solutions refined by evolution that have made the brain a highly efficient task performing system, for the brain is capable to carry out operations at a low energy expense and with a high speed unmatched by computers. In this article we explore the possible operations performed by astrocytes to efficiently integrate information from different neurons, we explain the implications of these tasks in higher brain functions, as well an in the modeling of neural circuits with artificial intelligence, and we present a roadmap to advance knowledge of astrocytes as building blocks of neural circuits.

  •   Chemically identifying molecules through ballistic electron energy losses (2020)

    García de Abajo, Francisco Javier (ICFO)

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      Chemically identifying molecules through ballistic electron energy losses

    Infrared absorption spectroscopy is routinely used to detect minute concentrations of molecules by analyzing and studying the molecular vibrational and electronic excitations. This technique has proven to be an excellent candidate for applications in areas such as medical diagnosis and detection of hazardous substances. However, because the wavelength of the infrared light used to detect the molecules is several microns, while the sample measures only a few Angstroms, molecular vibrations are excited by light with low efficiency, thus limiting this method in spatial resolution. In this study, we report on a novel approach that can chemically identify amounts of molecules at the zeptomol level (one 10-21 part of a mole, or about 600 molecules of a substance). We propose a device that uses ballistic electrons moving within a 2D semiconductor to detect and chemically identify the molecules. Instead of using photons to interact with the molecules, we use electrons that move ballistically in the semiconductor. 

    This approach is based on injecting electrons with well-defined energies through the device and having them interact with the analyte molecules placed close to the 2D-material. The interaction produces energy losses, which are directly associated with the fingerprints of the molecules. The 2D material is basically used for this purpose because it already provides vertical confinement of the electrons without the need of a vacuum chamber to run the experiment. The energy losses produced by interactions between the incident electrons and the analyte are then resolved in energy to generate a spectrum in the IR range, which exhibits the fingerprints of the molecules.

    This theoretical study demonstrates a new approach towards the identification of molecules at the zeptomol level. Through realistic simulations, we reveal a sensitivity down to the zeptomol level within a device of ~1 μm2 footprint, which could be integrated for massive multiplexing using currently available technology.