Destacados

Cada año, un comité de expertos debe acometer una ardua tarea: de entre todas las publicaciones de ICREA, debe escoger unas cuantas que destaquen del resto. Es todo un reto: a veces los debates se acaloran, y siempre son difíciles, pero acaba saliendo una lista con las mejors publicaciones del año. No se concede ningún premio, y el único reconocimiento adicional es el honor de ser resaltado en la web de ICREA. Cada publicación tiene algo especial, ya sea una solución especialmente elegante, un éxito espectacular en los medios de comunicación o la simple fascinación por una idea del todo nueva. Independientemente de la razón, se trata de los mejores de los mejores y, como tales, nos complace compartirlos aquí.

LIST OF SCIENTIFIC HIGHLIGHTS

Format: yyyy

  • Synchronisation revisited: first nanoscale demonstration (2019)

    Sotomayor Torres, Clivia Marfa (ICN2)

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    Synchronisation revisited: first nanoscale demonstration

    Synchronisation was discovered in 1665 by Lord Huygens reporting on his experiments on two pendulum clocks. So far synchronisation has been studied extensively at macroscopic scales. Not so in the nanoscale regime. And why not? Because it is challenging to obtain similar results in that regime: the design of the structures, the fabrication tolerances and the measurement methodology must be reproducible. Essential to spontaneous synchronisation between two systems are specific conditions: both systems must be self-sustained oscillators, meaning that they are able to generate their own rhythms, without the need of an external source. Moreover, they must synchronise due to a weak interaction, i.e., not because the systems are strongly connected. In our research these two conditions were unambiguously fulfilled for the first time, for two coupled nanobeams or optomechanical oscillators (see Fig. 1), which are 10 000 times smaller than Huygens’ pendulum clocks.  The coupling was engineered as a narrow beam at one end of the oscillators. Unlike Huygens’ pendulums, which were driven by the mechanical motion of the clock, our OM oscillators are driven to self-sustained oscillations by means of radiation pressure forces exerted on them by infrared lasers. Each oscillator, A and B, receives light from a different laser, reaching its own vibration frequency. Oscillator A is set to have stronger oscillations, i.e., a larger amplitude than oscillator B. The experiment shows that thanks to the design of the beam linking them, the frequency of B becomes that of A, thus achieving synchronisation.  We were able to control the collective dynamics (the synchronised state) and concluded that the more oscillators there are, the less noise the system generates, yielding better defined frequencies. 

    This research sets  a firm basis towards reconfigurable networks of nano-optoelectro-mechanical oscillators for applications in, e.g., neuromorphic photonic computing, a field of research that intends to imitate neurological structures to improve computation. 

  • A scientific journey from laboratory idea to new cancer therapy (2019)

    Soucek, Laura (VHIO)

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    A scientific journey from laboratory idea to new cancer therapy

    Everybody working in cancer research dreams of the ideal cancer drug that could attack cancer cells, but not normal tissues. However, the majority of our targets so far are in the most redundant compartments of cells that can quickly rewire to compensate for our attacks. Hence, novel opportunities might lie in the identification of less evolutionarily degenerate nodes in cancer. Some of these functions might be identified in the nuclei of cells (a compartment less accessible to standard drugs), where many proteins are intrinsically disordered, lacking a defined three-dimensional structure amenable to attack by canonical small molecule inhibitors. But are these challenges sufficient to dismiss these targets as “undruggable”? Our answer is definitely not.

    In our last publication in Science Translational Medicine [1], we established the feasibility of pharmacologically targeting MYC, the most infamous “undruggable target” deregulated in the majority of human cancers, by making use of a cell-penetrating polypeptide called Omomyc. I designed Omomyc when I was still a student, and I used it in genetically engineered models to establish the therapeutic potential of MYC inhibition to stop tumor progression. However, Omomyc was deemed too bulky and unfit to ever become a drug. And this is where our last publication is really proving this assumption wrong.  In [1], we showed that a purified, recombinantly produced Omomyc polypeptide has cell-penetrating properties and is disruptive in multiple ways: not only can Omomyc sequester MYC in complexes unable to recognize DNA, but it shows a dramatic therapeutic effect in Non-Small lung cancer, while displaying safety and lack of toxicity even upon long term treatment.

    Overall, our results provide the first evidence and preclinical validation of the Omomyc mini-protein as an excellent candidate for clinical development. Indeed, clinical trials are now planned for Q1 2021 to test its clinical value in patients.

  • Scientific Innovation and Scientific Rationality: A Conceptual Explication and a Dilemma (2019)

    Sturm, Thomas (UAB)

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    Scientific Innovation and Scientific Rationality: A Conceptual Explication and a Dilemma

    Scientists are often asked to promote innovation and aid society by, for instance, novel drugs and therapies, means of communication, ways of making technical devices more energy efficient, or methods for teaching mathematics to schoolchildren. Increasingly, they are also invited (if not urged) to innovate science itself. Universities, grant agencies, and governments encourage researchers to devise novel questions, methods, concepts, theories, goals, instruments, and even research institutions. But while the terminology of innovation is widely used, all too often this is rhetorical rather than reflective. The article aims to foster philosophical debate concerning scientific innovation. 

    As with innovations in markets, we can usefully view scientific innovation as one stage within a larger process from invention to diffusion; more specifically, innovation is a consequence of those inventions that are recognized as useful for changing research in non-incremental ways. However, unlike ‘discovery’, ‘innovation’ applies to elements that make possible, but do not by themselves establish or guarantee, correct research outputs. Most importantly, we assume that innovations are deliberately prepared and accepted, given that they imply violations or revisions of established rules of science. In this sense, innovation presupposes at least minimal rationality. This, however, leads to a tension between two plausible claims: (1) scientific innovation can be explained rationally; (2) no existing account of rationality explains scientific innovation. In particular, I argue that neither standard nor bounded theories of rationality can deliver a satisfactory explanation of scientific innovations. At the moment, it is unclear with what to replace them. Thus, despite our legitimate interest in scientific innovation, calls for research proposals and submissions should be formulated in more reflective and careful ways; and  we should not be excessively optimistic concerning our ability to rationally predict and steer the future direction of the scientific enterprise.

  • Making sense of nonsense mutations in disease using machine learning (2019)

    Supek, Fran (IRB Barcelona)
    Lehner, Ben (CRG)

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    Making sense of nonsense mutations in disease using machine learning

    Mutations in DNA can disrupt protein synthesis, sometimes causing truncated proteins which don’t work as intended. Known as nonsense mutations, these types of alterations can give rise to hereditary diseases and different types of cancer. To keep the number of truncated proteins to a minimum, human cells recognise and remove RNAs with nonsense mutations through a quality control process known as nonsense-mediated mRNA decay (NMD).

    To better understand the effect of NMD on human disease, we have built NMDetective, a tool describing every possible nonsense mutation that can occur in the human and mouse genomes.  Developed by large-scale statistical analyses based on machine learning, the algorithm identifies which mutations in the genome are susceptible to NMD.

    As described in Nature Genetics, we used NMDetective to analyse thousands of genetic variants that are known to give rise to hereditary diseases in humans. We were surprised to observe that, in many cases, NMD activity was actually predicted to lead to a greater severity of the disease. This suggests that pharmacological NMD inhibition could slow the progression of many different genetic diseases. To distinguish which patients would benefit from this therapy, it is necessary to apply a precision medicine approach to determine the mutation responsible for the disease and the effect of NMD on this mutation, and this is precisely where NMDetective comes into play.

    We also studied the role of NMD in cancer and the interaction between the tumour and the immune system. Remarkably, there is robust genomic evidence that NMD activity is important for the prediction of success of immunotherapy in cancer, because NMD hides mutations that would otherwise trigger the immune system. Therefore, NMDetective can be used to analyse the mutations present in the tumour, in order to better distinguish between cancer patients that respond to immunotherapy from those who do not respond to immunotherapy.

  • Powering the Internet of Things Revolution with Heat (2019)

    Tarancón Rubio, Albert (IREC)

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    Powering the Internet of Things Revolution with Heat

    The Internet of Things (IoT) has been identified as one of the five technologies that will change the world with billions of devices to be installed in the next decades. The massive deployment of miniaturized wireless sensor nodes will revolutionize the way we understand complex systems and our interaction with reality, which will bring new perspectives to the human progress. But how exactly this revolution will be powered remains an open question. Primary batteries currently represents the only practical solution existing for powering autonomous embedded systems but their intrinsic limitations to miniaturization and well-known environmental downsides if spread without adequate disposal, make them a short-term solution. Alternatively, self-powered integrated systems able to harvest energy present in the ambient- that is, waste heat- keep the advantages of batteries (low cost, easy installation, topological flexibility, suitability for movable parts, etc) while overcoming their major issues (long lasting, potentially biodegradable, maintenance free, etc). 

    One of the limiting factors in the development of micro power sources able to generate electricity from thermal gradients has been the inherent incompatibility of good thermoelectric materials such as bismuth and lead tellurides with silicon microfabrication technologies. However, ten years ago enhanced thermoelectric properties of silicon nanostructures were reported opening the door to the development of such micro thermoelectrical generators. In 2012, our team was the first implementing silicon nanowires in an efficient device. This year, we were able to reach values of power in the range of the IoT applications by using silicon-germanium alloys. This remarkable achievement should be considered as a first step for stimulating further work on the development of novel energy autonomous microsystems. Fabricating these new harvesters at low cost in batch mode will represent the last step for the desired IoT revolution also encouraging research towards powering any kind of autonomous and intelligent system like, why not, an autonomous thermal brain.

  • A new tool to play with interfaces for energy and information technologies (2019)

    Tarancón Rubio, Albert (IREC)

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    A new tool to play with interfaces for energy and information technologies

    Interfaces and surfaces are the site where the action happens, especially in the field of energy where catalytic reactions, adsorption of molecules, fast movement of charges or many other relevant phenomena take place in the limit between two different media or hetereogeneities of the same. 

    The unique features of interfaces made them rich in unprecedented phenomena ocurring. These new phenomena happening at interfaces are prevailing in the so-called interface-dominated materials such as nanostructures, where the boundaries are maximized compared to the volume. This novel class of materials are the object of study for new emerging disciplines like Nanoionics or Iontronics, in relation to ions, being the main source of breakthrough concepts to impulse new technologies that meet today's challenges. 

    We recently discovered a completely new strategy for engineering charge transport phenomena at the interface level by controlling the local non-stoichiometry of the compound. This new tool allows radically changing the nature of the charge transport of a material only by playing with its interfaces. A couple of works published in Advanced Materials (cover image) and APL Materials were released this year presenting this approach applied to manganites, which are extremely relevant materials for a collection of devices in the field of energy and information technologies. 

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