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

  • Cost-efficient nanodevices for pathogens detection (2019)

    Merkoçi, Arben (ICN2)

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    Cost-efficient nanodevices for pathogens detection

    There is an urgent need for the development of cost-efficient devices for in-field detection of pathogens. Nanobiosensors are a very good alternative for such applications. The first example is an integrated label-free in situ isothermal amplification/detection based on the use of screen-printed electrodes modified with gold nanoparticles and employing impedance for diagnostic of a plant disease (Citrus tristeza virus, CTV). The developed in-situ isothermal amplification/detection sensor showed advantages in terms of simplicity, sensitivity, and portability together with allowing quantitative analysis of nucleic acid. The proposed biosensor is of high potential interest for in-field applications for plant pathogen early detection, which would overcome the limitations of classical molecular methods such as PCR (polymerase chain reaction). The second example includes a fast and reliable way to detect pathogenic bacteria. The developed assay is based on the conversion of an electrochemical signal into a more convenient optical readout for the visual detection of Escherichia coli (E.coli). By electropolymerizing polyaniline (PANI) on an indium tin oxide screen-printed electrode (ITO SPE), we achieved not only the desired electrochromic behavior but also a convenient way to modify the electrode surface with antibodies (taking advantage of the many amine groups of PANI). Applying a constant potential to the PANI-modified ITO SPE induces a change in their oxidation state, which in turn generates a color change on the electrode surface. The presence of E. coli on the electrode surface increases the resistance in the circuit affecting the PANI oxidation states, producing a different electrochromic response. Using this electrochromic sensor, we could measure concentrations of E. coli spanning 4 orders of magnitude with a limit of detection of 102 colony forming unit per 1 mL (CFU mL−1) by the naked eye and 101 CFU mL−1 using ImageJ software. In this work we show that merging the sensitivity of electrochemistry with the user-friendliness of an optical readout can generate a new and powerful class of biosensors, with potentially unlimited applications in a variety of fields.

  • Identifying the Achilles heel of RAS-malignant tumors (2019)

    Milán Kalbfleisch, Marco (IRB Barcelona)

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    Identifying the Achilles heel of RAS-malignant tumors

    More than 30% of all human tumors arise from mutations that encode a RAS protein essentially locked in a constitutively activated form. Despite more than three decades of effort by Academia and Industry, only recently have effective RAS inhibitors started to be identified. We have used the fruit fly Drosophila as model system to identify strategies to specifically eliminate tumor cells that activate this oncogene. We have presented evidence that RAS drives active cell proliferation through the regulation of the G1-S transition, induces DNA damage, and most interestingly, silences the response to this damage by blocking the DNA damage response (DDR) pathway as well as the induction of cell death by the tumor suppressor protein Dp53. Given the inherent induction of DNA damage and additional blockade of the DDR at different levels by the RAS oncogene, we have used genetic or chemical inhibition of ERK activity coupled to ionizing radiation as a therapeutic approach to selectively eliminate RAS-malignant tissues. In particular, we have used TRAMETINIB, a drug prescribed for human melanoma, to inhibit the ability of RAS to block cell death, thus leading to the elimination of malignant tumors—selectively and by cell death—without affecting the development of organs or the flies themselves. Our results open up the possibility of combining radiation therapies with RAS inhibitors to selectively eliminate tumor cells.

     

  • Single-photon, single-atom matchmaking (2019)

    Mitchell, Morgan W. (ICFO)

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    Single-photon, single-atom matchmaking

    Single trapped atoms are greatly valued in quantum technology. They are ideal standards because they are the same everywhere in the world, they make extraordinary sensors and clocks, and they can be used as nodes in quantum information networks and quantum computing. Because an atom is a truly tiny quantity of matter, special techniques must be used to interface them even to ordinary laser beams. In these works, we approached the problem of strongly coupling a single trapped atom to individual photons and to photon pairs. We built an optical system of four high numerical-aperture lenses around a single 87Rb atom held in an “optical tweezer” trap. This allowed us to shape the photons’ wave-fronts to match the atom’s radiation pattern, to ensure both efficient absorption of single photons by a single atom, and efficient collection of photons emitted by the atom. At the same time, we developed the world’s first source of entangled photon pairs, both of which are resonant to optical transitions in the 87Rb atom. These new technologies enable study of light-matter interactions at the level of individual quanta, of interest to both quantum technologies and other technologies based on light mattter interactions, e.g. super-resolution imaging.  

     

  • Accelerating the derivation of kidney organoids from human pluripotent stem cells (2019)

    Montserrat Pulido, Núria (IBEC)
    Trepat, Xavier (IBEC)

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    Accelerating the derivation of kidney organoids from human pluripotent stem cells

    The generation of organoids is one of the biggest scientific advances in regenerative medicine. Here, by lengthening the time that human pluripotent stem cells (hPSCs) were exposed to a three-dimensional microenvironment, and by applying defined renal inductive signals, we generated kidney organoids that transcriptomically matched second-trimester human fetal kidneys. We validated these results using ex vivo and in vitro assays that model renal development. Furthermore, we developed a transplantation method that utilizes the chick chorioallantoic membrane. This approach created a soft in vivo microenvironment that promoted the growth and differentiation of implanted kidney organoids, as well as providing a vascular component. The stiffness of the in ovo chorioallantoic membrane microenvironment was recapitulated in vitro by fabricating compliant hydrogels. These biomaterials promoted the efficient generation of renal vesicles and nephron structures, demonstrating that a soft environment accelerates the differentiation of hPSC-derived kidney organoids. This work has recieved the prestigious award Íñigo Álvarez de Toledo in Basic Nephrology 2019. It has also been highlighted as a News and Views in the same journal Nature Materials and as an Editorial Comment in the prestigious journal Nature Reviews in Nephrology.

  • Keep-on moving: Evaluating the multiple conformations of enzymes (2019)

    Osuna Oliveras, Sílvia (UdG)

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    Keep-on moving: Evaluating the multiple conformations of enzymes

    Enzymes are proteins that are capable of accelerating the chemical reactions by as many as seventeen orders of magnitude. These molecules that have the ability to speed reactions are called catalysts. 

    How do enzymes work? The understanding of the enormous catalytic power of biocatalysts still corresponds to one of the grand challenges of chemical biology. Experimental and computational evidences have demonstrated that enzymes can adopt multiple conformations in solution, which are key for their function. We have demonstrated that by evaluating the multiple conformations that enzymes adopt by means of computational tools such as Molecular Dynamics (MD) simulations their mechanism of action can be elucidated. Additionally, these simulations can be used for predicting which changes in their structure (mutations) are required for novel activity. 

    New target for liver cancer treatment: Our computational studies have provided further evidence for the structural and functional similarity between different p38 kinases. One of the kinase enzymes, p38gamma, was found to present similitudes with another group of proteins known as CDKs, which have been known for a long time to be responsible for regulating the cell division cycle. This study demonstrates that p38gamma could be a new pharmacological target for liver cancer.

     

    New enzymes for the synthesis of contraceptive hormones: Many of the drugs used to treat diseases have limitations in the production process. In most cases, many by-products are obtained that have no pharmacological activity, dramatically reducing the production efficiency. In a recent study we aimed to produce a key intermediate in the synthesis of drugs used as contraceptive hormones, Levonorgestel or Gestodene. X-ray crystallography studies together with computational tools made possible the design of a new Alcohol Dehydrogenase (ADH) enzyme for the efficient synthesis of the steroid hormone precursors. We found dramatic differences in the mobility of a region of the enzyme that was essential for enhancing the enzyme activity towards these industrially-relevant substrates. 

  • Changes in the CO2 regulating capacity of the Southern Ocean (2019)

    Pelejero Bou, Carles (CSIC - ICM)

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    Changes in the CO2 regulating capacity of the Southern Ocean

    Today, the world’s oceans absorb about one-third of the CO2 that we humans are putting into the atmosphere from the combustion of fossil fuels. Among them, the Southern Ocean is the one that contributes most to this sequestration. Almost half of all the oceanic CO2 uptake takes place in the Southern Ocean. This absorption is, of course, very positive; otherwise we would have significantly higher CO2 concentrations in the atmosphere, with the consequent enhanced global warming. However, the Southern Ocean has not always operated in this way. This is what we have discovered in this study, which provides a reconstruction of the CO2 regulating capacity of the Southern Ocean over the last 25.000 years. For this, we analyzed specific isotopic ratios of planktonic microfossils (Fig. 1) and several key organic compounds from a deep sea sediment core recovered south of Tasmania (Fig. 2). With these analyses we reconstructed the evolution of parameters such as seawater temperature (from long chain alkenones) and the acidity (from boron isotopes) in the past. With them, we calculated the variability of the dissolved CO2 in seawater which, by comparison with the record of atmospheric CO2 from Antarctica ice cores, allowed us to determine the CO2 sink or source role of the Southern Ocean during the last glacial to interglacial transition. The results show that the Southern Ocean surface waters in the studied location were a net sink for atmospheric CO2 during glacial times and up until about 12.000 years ago, when they became a net source of CO2 for about 8.000 years. In this varying regulatory role of the Southern Ocean, key factors were the changes in primary productivity and the intensity of marine currents. This study helps to understand the variability of this regulatory role of the Southern Ocean but also alerts about the future capacity of this ocean to continue to absorb CO2, which should not necessarily continue to be as favorable as today. In the event that its capacity to act as a CO2 sink decreased in the future, the global projections on the emissions of this greenhouse gas would be altered to even more alarming levels than the current ones.

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