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.


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  • Citizen science reveals first comprehensive snapshot of the oral microbiome through age and lifestyle factors (2022)

    Gabaldón Estevan, Toni (CRG)

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    Citizen science reveals first comprehensive snapshot of the oral microbiome through age and lifestyle factors

    Oral health is connected to the entire human body. For this reason, saliva contains a lot of useful information. The results of  the citizen-science project  'Saca la Lengua' provide a dictionary that helps interpret the language of the oral microbiome so that, one day, using a saliva test could be as routine as blood or urine tests. The study analyzed the saliva of 1,648 people between 7 and 85 years of age located all over Spain. The study found that teenagers have a highly biodiverse oral microbiome that varies greatly between individuals. Middle-aged people had lower biodiversity as well as a generally homogeneous composition, representing a stage of high stability. From the age of 60, biodiversity and the differences between individuals increased considerably due to the establishment of rare opportunistic species, almost all of which are linked to oral diseases such as periodontitis. To understand the environmental and/or lifestyle characteristics that influence the oral microbiome, study participants completed a questionnaire that examined 80 different aspects of lifestyle habits, diet, hygiene and health. Factors associated with major changes in the oral microbiome were found to be linked to chronic diseases such as cystic fibrosis or conditions such as Down syndrome, followed by lifestyle habits such as smoking. Each of these factors changed the microbiome in a particular way, resulting in a specific signal. People with celiac disease, hypertension or those that used antibiotics also changed their oral microbiome in specific ways, although to a lesser extent.The impact of social and family relationships also influenced the composition of the oral microbiome. Members of the same family – for example, parents and children, or two brothers or sisters – have a more similar microbiome compared to two people from different families. The association exists even among members of the same class in school, a finding that leads us to hypothesise that sharing the same environment, even for a few hours a day, can significantly affect the oral microbiome.

  • Understanding the dynamics of molecular condensates in living cells (2022)

    García Parajo, Maria F. (ICFO)

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    Understanding the dynamics of molecular condensates in living cells

    Phase separation is a physical mechanism by which two mixed liquids form distinct phases, just as the oil separates from water to form droplets. This phenomenon occurs in many different scenarios, ranging from biological systems to quantum matter. Strikingly, it has been recently shown that liquid-liquid phase separation regulates a multitude of biochemical processes in living cells by creating molecular condensates. These condensates operate as versatile biochemical hubs intervening in several aspects of cellular processes, promoting or damping biological reactions. 

    An important example of such condensates is the transcription factors (TF), proteins that bind to specific DNA sequences to regulate gene transcription. By forming phase-separated TF condensates the cell could promote gene expression at will. Although there has been some progress in understanding this phenomenon, studying phase separation in living nuclei at the required spatial and temporal resolution is extremely challenging. For this reason, the biophysics of transcription factor (TF) condensation remains highly unexplored with most experiments so far being restricted to either fixed cells or to in-vitro settings.

    In a joint collaboration between the groups of Miguel Beato at CRG, Maciej Lewenstein and Maria Garcia-Parajo at ICFO, we investigated the physics of TF condensates by combining single-molecule experiments with theory and simulations. Using cutting-edge single molecule approaches and machine learning algorithms we followed the diffusion, growth dynamics, and sizes of a particular type of TF condensates in living cells. We found that at a short times, condensates grow in a classical fashion as any phase-separated system. Intriguingly, at longer times, the condensates stopped growing and remained as nanoscale-sized droplets. By developing a theoretical model and performing extensive simulations, we demonstrated that condensate growth dynamics and nanoscale-size arrested growth is regulated by molecular escaping from condensates. This mechanism of stochastic escaping provides an exquisite control of condensate size in nonequilibrium systems such as living cells.


  • A quantum approach to engineering of two-dimensional metamaterials (2022)

    García de Abajo, Francisco Javier (ICFO)

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    A quantum approach to engineering of two-dimensional metamaterials

    Having new methods to synthesize previously non-existing materials constitutes a challenge with important consequences for technological progress in general. Unfortunately, there is a limited suite of methods for material design, essentially consisting in changing the chemical composition and the microscopic structure of already existing materials. This work introduces a disruptive approach to materials design, producing radical modifications in the electronic properties, the optical response, and the thermal conduction of a thin atomic layer, and essentially rendering a previously non-existing material. The new method relies on imprinting a so-called quantum phase on the material’s electrons by means of non-contact interaction with an external structure. The latter does not need to produce external fields, in contrast to electric or magnetic doping schemes, so the present approach is highly noninvasive. This method is thus exploiting a genuinely quantum effect to modify, with a substantial degree of control, the material’s properties. In particular, the work demonstrates, based on rigorous theory, that electronic gaps are opened in a doped thin superconductor by the aforementioned quantum interaction with a neighboring neutral structure, and this in turn produces radical changes in the optical response, as well as a metal-insulator transition in its electrical behavior, accompanied by a thermal conductor-insulator transition. In brief, this work introduces a viable, disruptive, conceptually novel approach to materials design, thus enriching the limited suite of tools that are currently available to engineer materials for application in the design of nanodevices.

  • Ferroelectricity or ferroelasticity? That is the question about metal halide perovskites (2022)

    Goñi, Alejandro R. (CSIC - ICMAB)

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    Ferroelectricity or ferroelasticity? That is the question about metal halide perovskites

    Since the irruption of metal halide perovskites (MHPs) in the field of photovoltaics (PV) about a decade ago, these semiconductor materials have been the focus of attention worldwide. They triggered an intense research activity among scientists striving for a steady increase in energy conversion efficiencies, which have recently reached values beyond 25%. MHPs are really attractive because they are produced and processed by scalable, low-cost, energy-saving solution-based methods like organic semiconductors but they exhibit optoelectronic properties rivaling those of their inorganic counterparts. The nature of the peculiar optoelectronic properties underlying such astounding performance is still controversial. The existence of ferroelectricity in MHPs and its alleged impact on photovoltaic activity have fueled an intense debate, in which unanimous consensus is still far from being reached.

    The aim of this work is two-fold: On one hand, we finally settle the controversy about ferroelectricity by exposing the main experimental and theoretical facts and revising their interpretation from the alternative point of view of ferroelasticity. In particular, we aim to convey the message that a ferroelectric polarization cannot be sustained when the A-site cation dynamics is fully unleashed, in frank contrast to the formation of ferroelastic domains. On the other hand, we discuss the possible impact of the ferroic behavior of MHPs on the charge-carrier generation and transport, taking into account the magnitude of the observed effects in comparison with competing ones like polaron formation and ion migration.

  • A study model for Ewing sarcoma in Drosophila (2022)

    González Hernández, Cayetano (IRB Barcelona)

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    A study model for Ewing sarcoma in Drosophila

    Ewing sarcoma is the second most frequent bone tumour in children, adolescents, and young adults. There is no specific treatment for this disease and the long-term survival of patients with metastatic or relapsed Ewing sarcoma is very low.

    Ewing sarcoma is caused by a single oncogene that results from the fusion of two genes. Although a variety of genes may be involved, the  fusion protein oncogene EWS-FLI is the most frequent . All attempts to develop experimental animal models of Ewing sarcoma in mice (expressing the EWS-FLI oncogene) have failed.

    Prompted by the need for a genetically tractable model that could be used to study the disease, we have teamed up with trhe laboratory of Dr. Jaume Mora, scientific director at the IRSJD Pediatric Cancer Center Barcelona (PCCB), to  engineer Drosophila transgenic strains that express a mutant variant of the human oncogene called EWS-FLIFS. Remarkably, we have found that expression of the human EWS-FLIFS protein in certain types of Drosophila cells triggers the same oncogenic pathways known to account for EWS-FLI oncogenic activity in human patients.

    Building upon their new transgenic Drosophila line, we have rewired two oncogenic pathways used by EWS-FLI, such that when triggered by the presence of EWS-FLIFS, they result in the expression of a fluorescent protein that would otherwise never be expressed. Thus, rather than tumour growth, wes use fluorescence as a read-out of EWS-FLI oncogenic activity. This simple genetic trick greatly facilitates the implementation of massive genetic and chemical screens to identify "modifiers" that inhibit EWS-FLI's oncogenic activity as inhibitors of the appearance of fluorescence.

    Genetic screens based on this new model will make it possible to discover critical proteins required for EWS-FLI to exert its oncogenic function, hence expanding our knowledge of the molecular basis of the disease, as well as identifying new putative therapeutic targets.  Chemical screens may identify compounds that could serve as lead molecules for the development of therapeutic drugs.



  • How does the cell open and close electron taps? (2022)

    Gorostiza Langa, Pau (IBEC)
    Rovira Virgili, Carme (UB)

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    How does the cell open and close electron taps?

    Researchers at the Institute for Bioengineering of Catalonia (IBEC) have achieved a nanoscale view of the electron transport between redox partner proteins of the respiratory chain, allowing for a better understanding of their regulation by phosphorylation.

    Mitochondria play a key role in cellular energy production. They are membrane-bound cell organelles found in almost all eukaryotic cells (animals, plants, and fungi). Their main function in animal cells is to convert nutrients into chemical energy, stored in the form of adenosine triphosphate molecules, through a process called cellular respiration, which includes a tightly regulated electron transport chain. In addition to this function, mitochondria are also responsible for other functions, such as inducing cell death in response to stress events. How does the cell open and close the "taps" that control electron transport through these processes?

    A previous study by IBEC demonstrated that the transfer of electrons between mitochondrial proteins cytochrome c and cytochrome bc1takes place at a distance through the aqueous solution, via a charge conduit established between them. This new study reveals how this process is regulated by phosphorylation (addition of a phosphate group near the redox active site of cytochrome c).

    The researchers combined the analysis of electron transport at the molecular level with the measurement of protein-protein interaction forces, leading to a better understanding of the effects of cytochrome c phosphorylation on the molecular regulation of the mitochondrial respiratory chain. They discovered that phosphorylation impairs electron transport by disrupting the charge conduit and increasing the affinity between cytochrome c and cytochrome bc1, thus leading to the formation of bottlenecks in the process, and slowing the flow of electrons in the chain.

    These results also highlight the biological relevance of long-distance charge transport between redox proteins through the aqueous solution and contribute to the understanding of interprotein electron transfer.