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

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  • Infections Contribute to More Than Half of Child Deaths in Developing Countries (2020)

    Bassat Orellana, Quique (ISGlobal)

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    Infections Contribute to More Than Half of Child Deaths in Developing Countries

    The Child Health and Mortality Prevention Surveillance (CHAMPS) network published in 2020 its initial scientific findings, providing reliable data on the causes of death in children under five years of age and stillborn foetuses in five settings in Africa and Asia. The study was co-led by the Barcelona Institute for Global Health (ISGlobal), together with Emory University in Atlanta and the US Centers for Disease Control and Prevention.

    Minimally invasive autopsies were performed on 933 deceased neonates, children <5 years of age and stillborn foetuses at five sites in Bangladesh, Kenya, Mali, Mozambique and South Africa. This autopsy method, developed several years ago by ISGlobal, allows the cause of death to be determined with high precision through the analysis of postmortem tissue samples.

    Notably, the authors of the study were able to describe the entire chain of events leading to death. Two or more conditions were identified in the causal chain for 63% of cases and infection contributed to death in 54% of cases. One of the key features of this study is the granularity of the data we obtained. We were able to identify the infectious pathogens involved and associate them with the histopathological abnormalities observed in the organ tissue. This gave us an almost three-dimensional picture of the processes that led to death, and in a less invasive way than conventional autopsy techniques.

    The high prevalence of Klebsiella pneumoniae in a considerable number of cases of pneumonia, sepsis and meningitis was a key finding of the study. This information could drive the development of new tools and strategies for the prevention or treatment of this pathogen.

    A detailed understanding of all the factors involved in child deaths is essential to estimate the burden of disease, track global progress and develop efficient, cost-effective and, most importantly, evidence-based policies to combat child mortality. The CHAMPS studies will mark a turning point in these efforts, since they provide crucial information for the design and implementation of life-saving health interventions.

  • COLORECTAL CANCER EXPANDS FROM BIOSYNTHETIC CELL NICHES (2020)

    Batlle Gómez, Eduard (IRB Barcelona)

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    COLORECTAL CANCER EXPANDS FROM BIOSYNTHETIC CELL NICHES

    Tissue homeostasis requires controlled protein synthesis rates, and distinct cell types in healthy tissues exhibit different biosynthetic capabilities. In tumors, this regulation is disrupted by oncogenic alterations, many of which enhance the cell biosynthetic machinery, including ribosomal DNA transcription, ribosomal biogenesis, and protein production rates. We however discovered that the vast majority of ribosomal RNA and proteins synthesized in colorectal cancer (CRCs) are contributed by a limited subset of cells positioned immediately adjacent to the stroma. We showed that tumor cells that reside in these biosynthetic niches function as cancer stem cells although often they do not express LGR5 or other stem cell marker genes. In contrast, tumor cell differentiation is characterized by pervasive and permanent loss of biosynthetic capacities. To investigate the role of biosynthetic cells in CRC, we developed a methodology based on the use of CRISPR/Cas9 to edit the genomes of patient-derived organoids to introduce cell-specific ablation cassettes. Using this strategy in CRC models, we showed that lack of the biosynthetic cell compartment irreversibly halts tumor growth and induces tumor differentiation. We propose that zonation patterns of ribosomal DNA transcription and protein synthesis in CRC reflect the existence of a simple stem cell-like hierarchy based on the differential biosynthetic capacity of tumor cells. This model challenges some widely accepted views on the identity and features of stem cells in CRC and may inspire new therapeutic approaches.

  • Bottom-up effects from phytoplankton on fish production in lakes (2020)

    Brucet, Sandra (UVIC)

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    Bottom-up effects from phytoplankton on fish production in lakes

    All ecosystems, and aquatic ones are no exception, are made up of different trophic levels. Predator-prey relationships that are established between more than two of these levels are called trophic cascades and can significantly alter the functioning of ecosystems. These cascades, one of the most studied concepts in ecology, are the topic of the article Energy-based top-down and bottom-up relationships between fish community energy demand or production and phytoplankton across lakes at a continental scale, published by our group.

    Our work analyzes the magnitude of trophic cascades from an energy point of view in lakes using samples from 227 European lakes. The results suggest that bottom-up effects have more effect on ecosystems than top-down effects. That is, the observed effects of primary producers (i.e., those that are food for other species but do not feed on any of them) on the fish that inhabit the lakes are substantially stronger than the effects that fish can produce on these primary producers.

    To reach these conclusions, we used the Metabolic Theory of Ecology to estimate the metabolic metrics of each fish community, as well as to calculate the energy demand and production of each community. From each of the lakes analyzed, we quantified the magnitude of the trophic cascades and established in which direction they have the greatest impact on the ecosystem. In addition, for the first time, generally neglected effects have been taken into account in the comparison of trophic cascades between ponds, such as the metabolic activity of fish. The results are important for the management of the ecological status of European lakes.

  • Energy multi-harvesting with halide perovskites: two for the price of one (2020)

    Catalán Bernabé, Gustau (ICN2)
    Stengel, Massimiliano (CSIC - ICMAB)

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    Energy multi-harvesting with halide perovskites: two for the price of one

    Capturing energy from the environment (aka energy harvesting) is a very active area of research on account of its usefulness for powering sensors, devices in inaccessible locations, or just generally reducing our dependence on non-renewable energy sources. Two of the most common energy-harvesting mechanisms are photovoltaics, which convert sunlight into electricity, and electromechanics, which convert mechanical vibrations into electricity.  These two phenomena are based on, respectively, semiconducting junctions and piezoelectric insulators. Unfortunately, the different material families on which these phenomena are based complicate their integration into single devices.

    This situation, however, has just changed with the discovery of a new effect, photoflexoelectricity, whereby photovoltaic semiconductor materials not only generate electricity when they vibrate, but the amount of electricity generated by the vibration multiplies by orders of magnitude under illumination. In a collaboration between several groups in China, the US and Catalonia, we have shown that halide perovskites, a family of highly efficient photovoltaic materials, display a photoflexoelectric effect whereby their bending-induced electricity is enhanced by light. We also show that photoflexoelectricity is not exclusive to halides but a general property of semiconductors. Photoflexoelectricity thus enables simultaneous electromechanical and photovoltaic energy harvesting in already commonly used photovoltaic materials and has the potential to revolutionize the field of energy harvesting.

  • Potential Applications of Plant Biotechnology against SARS-CoV-2 (2020)

    Christou, Paul (UdL)

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    Potential Applications of Plant Biotechnology against SARS-CoV-2

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for an ongoing human pandemic (COVID-19). There is a massive international effort underway to develop diagnostic reagents, vaccines, and antiviral drugs in a bid to slow down the spread of the disease and save lives. One part of that international effort involves the research community working with plants, bringing researchers from all over the world together with commercial enterprises to achieve the rapid supply of protein antigens and antibodies for diagnostic kits, and scalable production systems for the emergency manufacturing of vaccines and antiviral drugs. Here, we look at some of the ways in which plants can and are being used in the fight against COVID-19.

     

  • A system to induce sexual conversion in malaria parasites (2020)

    Cortés Closas, Alfred (ISGlobal)

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    A system to induce sexual conversion in malaria parasites

    Transmission of malaria from an infected human to a mosquito vector requires that some of the asexually-growing parasites in the blood convert into sexual forms called gametocytes, which are the only form of the parasite that can infect mosquitoes. Gametocytes are resistant to the majority of antimalarial drugs that effectively kill disease-causing asexual forms, implying that successfully treated malaria patients can continue transmitting the disease for several days or even weeks. Therefore, the success of malaria control and eradication efforts largely depends on being able to develop drugs that are effective against gametocytes. This will require a better knowledge of gametocyte biology, but studies on gametocytes are hampered by their low relative abundance and because early sexual forms are morphologically undistinguishable from their asexual counterparts, from which they cannot be separated.

     

    In this article we describe the use of CRISPR-Cas9 technology and an inducible recombinase to generate Plasmodium falciparum parasites in which expression of the master regulator pfap2-g can be conditionally induced, resulting in massive sexual conversion (Fig. 1). Using these engineered parasite lines, we obtained >90% pure, synchronous populations of parasites at the initial stages of sexual development, including previously elusive sexually committed schizonts and sexual rings. To demonstrate the utility of the system, we provide a detailed transcriptomic and phenotypic characterization of these developmental stages, which identified the specific upregulated and downregulated genes that mark early sexual development. Our system will enable the characterization of early gametocytes at multiple additional levels, and also efficient screening of drugs against parasites at different stages of sexual development.

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