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

  • Breaking paradigms of enzyme action to fight plant pathogens (2021)

    Rovira Virgili, Carme (UB)

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    Breaking paradigms of enzyme action to fight plant pathogens

    When talking about glycosidases – the main enzymes responsible for degrading carbohydrates in Nature – one often refers to the “catalytic itinerary”. This is the set of chemical and structural modifications that a certain substrate (typically a carbohydrate molecule) undergoes while it is being cleaved by the enzyme (broken into pieces). One of the main features of the catalytic itinerary is the “shape” or conformation of the substrate, i.e. the so-called “conformational catalytic itinerary”.

    Until now, it was assumed that the conformational catalytic itinerary was unique for each glycosidase enzyme (and even for all members of the same family of enzymes).  By means of a multidisciplinary work involving protein crystallography and quantum mechanics/molecular mechanics simulations, we demonstrate that this paradigm breaks for certain enzymes acting on hemicellulose (a polysaccharide of plant cell walls). Exo-oligoxylanases from the pathogen Xanthomonas citri – classified in the family 43 of glycosidases - can cleave the terminal end of plant carbohydrates via two alternative catalytic itineraries.

    These results will serve to find ways to redesign glycosidase active sites (the region of the enzyme that binds and converts the substrate in a product), as well as designing inhibitor molecules that suppress the enzyme activity to fight the pathogen.

    The work is a collaboration between researchers from the Brazilian Biorenewables National Laboratory (Campinas, Brazil), led by Mario Murakami, and the group of Quantum Simulation of biological Processes of the Department of Chemistry of the University of Barcelona, led by Carme Rovira.

  • BioEngineering Hybrid Robotics across different length scales: from Nanobots to Biobots (2021)

    Sánchez Ordónez, Samuel (IBEC)

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    BioEngineering Hybrid Robotics across different length scales: from Nanobots to Biobots

    Our group has reported two unprecedented, bioengineered hybrid robots at different length scales, ranging from the nano- to the millimeter-scale, in the prestigious journal Science Robotics. Hybrid robots combine biological and artificial components in a single system.

    At the nanoscale, we demonstrated that nanoparticles coated with urease enzyme (so called nanobots) swim in urea solutions naturally present in the bladder of a mice. It is of extreme importance to track swarms of nanobots moving in vivo, since millions of them are required to treat specific cancer pathologies. To do so, we used of Positron Emission Tomography (PET) at CIC biomaGUNE, a high-sensitive non-invasive technique extensively used in the biomedical field. This technique allows the observation of radiolabelled nanobots in the bladder of mice like never before. Nanobots actively move in 3D, reaching the walls of bladder where tumors are typically located, something not achieved with passive nanoparticles or current treatments. This work constitutes a fundamental advance in the race of nanobots to become a key technological player in precision medicine.

    At a larger scale, we combined skeletal muscle cells and hydrogels using 3D printing for the development of living robots (biobots) swimming at extraordinary velocities. We took advantage of the spontaneous contraction of muscle cells to mechanically self-train them, becoming stronger muscle-based swimmers. We integrated a compliant skeleton with a serpentine spring shape, designed and optimized via simulations. This innovative scaffold provides mechanical self-stimulation, without the need of any external input obtaining a biobot which moves 791x faster than any reported skeletal muscle–based biobots. This research opens the door to a new generation of stronger and faster biological robots based on muscle cells not only for environmental, drug delivery and/or drug testing purposes, but also for the development of bionic prosthetics.

  • Hot spots? No, thank you! (2021)

    Sotomayor Torres, Clivia Marfa (ICN2)

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    Hot spots? No, thank you!

    Thermal transport by phonons is at the heart of materials research for energy harvesting applications, such as thermoelectricity, and thermal management in electronic and optoelectronic devices. The quest for more abundant and less toxic materials has turned to 2-dimensional (2D) materials and among them SnSe2 holds a promise with exceptional figures of merit ZT, eg., 2.95 at 800 K. To integrate thermoelectric generators in circuits, the challenge of controlling the heat directionality becomes increasingly important. Thus, the study of heat propagation in two-dimensional materials is highly relevant to assess their potential for applications that pose thermal management constraints. 

    We report a systematic study of the in-plane and cross-plane thermal conductivity of supported and suspended crystalline SnSe2 films of thickness from 16 to 190 nm, with state-of-the-art Raman thermometry and frequency domain thermoreflectance (see figure 1). The specific crystalline structure of materials determines their capacity of conducting heat along different directions, as in the case of SnSe2.

    This work revealed that the thermal conductivity anisotropy ratio of the in-plane and cross-plane conductivities, is almost a factor of 10 and is independent of the SnSe2 film thickness in the range studied. This means that heat tends to propagate faster along the in-plane direction than along the cross-plane one. Moreover, the in-plane thermal conductivity drops when the ambient temperature increases, but this temperature dependence is weaker for thinner films (see figure 2). A full explanation is provided in terms of the phonon mean free path distribution for different thickness values and  the role of surface phonon scattering. 

    This study yield useful information on heat transport in SnSe2, which can help design electronic lab-scale devices with improved thermal management when it is desirable to have heat dissipating mainly in one direction, while preserving thermal insulation in the other. This may be a way to avoid hot spots and improve device stability and performance. 

  • Electrostatics and electromechanics in two-dimensional crystals (2021)

    Stengel, Massimiliano (CSIC - ICMAB)

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    Electrostatics and electromechanics in two-dimensional crystals

    Electrons in insulating crystals polarize in response to an externally applied electric field, resulting in a partial suppression of the field amplitude; such a phenomenon is known as “dielectric screening.” While much effort has gone into developing a quantitative understanding of this behavior and its impact on materials properties, 2D crystals remain challenging to describe by means of established modeling strategies. Analytical solutions for the idealized “strict 2D” limit do exist, but a fundamental theory that accounts for the “quasi-2D” nature of real layers is still missing. Here, we develop an exact theory of the long-range electrostatics in quasi-2D systems, enabling an accurate modeling of any physical property (such as interatomic forces at large distances) that depends on them.

    Our main mathematical result consists of achieving a sound and compact decomposition of the Coulomb interactions between long-range and short-range contributions in the quasi-2D case, thereby extending and generalizing existing approaches and providing them with a solid foundation. To do this, we rely on only two simple and intuitive formal devices: the well-known image-charge method of classical electrostatics and the bisection formula of the hyperbolic trigonometric functions.

    Our formalism provides a general platform for describing both intralayer and extralayer electrostatic interactions in 2D systems, with an applicability that goes well beyond the specifics of lattice dynamics. As a first application, we demonstrate its usefulness in describing higher-order electromechanical couplings, such as flexoelectricity. (The latter refers to the macroscopic polarization induced by strain gradients, e.g., flexural deformations of a 2D layer.) We find that both the direct and converse effect are described by a universal coupling constant, encompassing purely electronic and lattice-mediated contributions. Within the former, we identify a key metric term, consisting in the quadrupolar moment of the unperturbed charge density. We propose a simple continuum model to connect our findings with the available experimental measurements.

  • Theories of Rationality and the Descriptive/Normative divide: A Historical Approach. (2021)

    Sturm, Thomas (UAB)

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    Theories of Rationality and the Descriptive/Normative divide: A Historical Approach.

    This article from the new landmark MIT Handbook of Rationality, considers the history of the descriptive–normative divide, viewed as fundamental to, but also challenging, current research on rationality. This history can be subdivided into three main stages: First, from antiquity to early modernity, despite important contributions to theories of rationality by Plato, Aristotle, and others, the descriptive–normative distinction existed only implicitly and thus never became a topic of discussion. That changed, secondly, during the Enlightenment, through a mixture of new metaphysical and scientific ideas, and due to philosophical struggles over the nature, potential, and limits of rationality. The descriptive–normative distinction became prominent and problematized. This started in ethics, through David Hume’s is–ought divide, also called "Hume's guillotine": we can state what a person's belief, desire or action IS, but it does not follow that the person SHOULD hold the belief or desire or commit that action. Hume's guillotine, however, was fraught with problems. In Immanuel Kant, we find more sophisticated uses of the is–ought distinction, fed by the beginnings of empirical research into thinking and decision making and by a deeper understanding of what moral thinking is about. This was related to competing accounts of rationality. Hume championed a narrowly epistemic account of reason, so that practical reasoning concerns only the means for pursuing our passions; we cannot ask what passions we ought to have. Kant argued that our passions are subject to rational criticism as well and, moreover, that we must draw the is-ought distinction not only with resepct to actions but to thinking as well. Thus emerged the ideas that ethics, logic and epistemology are (in part) normative disciplines. In a third stage,  Kant's views became revived but also criticized since the 19th-century psychologism debate; this shapes discussions over how empirical and normative aspects of human rationality are to be studied in philosophy and psychology today.

  • A new target gene to treat hyper-mutated lung cancers by disabling DNA repair (2021)

    Supek, Fran (IRB Barcelona)

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    A new target gene to treat hyper-mutated lung cancers by disabling DNA repair

    Many tumours bear a high number of mutations due to an antiviral defence mechanism, the APOBEC family of enyzmes. This can accidentally activate during carcinogenesis, due to largely unknown causes, damaging DNA and causing abudnant mutations. Healthy somatic cells of various tissues, remarkably, rarely exhibit APOBEC mutagenesis, suggesting that APOBECs could provide a novel way to selectively target malignant cells while sparing healthy ones.

    We have found that the HMCES enzyme – a recently discovered DNA damage sensor – to be the Achilles heel of some lung tumours, specifically those with a highly active APOBEC3A system.  Our study found that blocking HMCES is very damaging to cells with an expressed APOBEC3A enyzme (which are many lung cancer cells), but much less so for the genetically identical cell line but in which APOBEC is switched off.  In addition to the lung adenocarcinoma, APOBEC3A enzyme mutagenizes other cancer types, most notably breast, head-and-neck and bladder cancers and sarcomas, suggesting a broad application of this finding. 

    Genetic screening experiments were performed using CRISPR/Cas9 on several types of human lung cancer cell lines, which we engineered to mimic tumors in their ability to overexpress APOBEC3A and cause DNA damage and mutations. The HMCES gene was a recurrent 'hit' in this genome-wide search.  Moreover a genomic analysis across ~100 cell lines indicated that APOBEC-mutated cells of diverse genetic backgrounds poorly tolerate editing of the HMCES gene.  This supported that HMCES can provide a therapeutic avenue, effective in different individuals.  Additionally, in a genetic screen in cells where the TP53 gene was ablated (a common occurence in tumors, but a rare one in noncancerous somatic cells), the effects of HMCES inhibition were boosted.

    Overall, inhibiting HMCES may selectively destroy the hypermutating, rapidly evolving cells within a lung tumor mass, hampering the cancer's ability to adapt to drug treatments and to gain new driver mutations.  We suggest that new approaches to cancer therapy might focus on targeting hypermutating cells to slow down tumor evolution.

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