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 24 publications 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
  • Deciphering the mechanism that determines organ size and shape (2020)

    Milán Kalbfleisch, Marco (IRB Barcelona)

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    Deciphering the mechanism that determines organ size and shape

    Morphogens are distributed throughout tissues in a concentration gradient, informing cells about the "location” within a tissue and providing instructions on how these cells should develop. Several studies have reported that these morphogens are also responsible for the growth of these tissues. While the presence of morphogens along a gradient defines the spatial distribution of the different structures, the study headed by the Milán lab has used the developing wing primordium of Drosophila to demonstrate that the gradient itself is not indispensable to promote growth. The two morphogens addressed in this study, namely Dpp and Wg (the orthologues of BMP and Wnt in vertebrates), promote the growth of the fly wing, but through two independent and non-interchangeable pathways. Dpp stimulates growth along the anteroposterior axis in a unique and exclusive manner, while Wg favours proliferative activity along the proximodistal axis.  The work carried out by Lara Barrio and Marco Milán demonstrates that the capacity of these morphogens to promote growth in two distinct directions is due to their restricted  expression in two perpendicular bands and to the need for both to be present for the tissue to grow. These findings thus reveal the mechanism through which organ proportions are regulated by morphogen activity. Given the high genetic and mechanistic conservation between flies and humans, these discoveries pave the way for new research lines into congenital malformations and other diseases

  • Entanglement of 15 trillion hot, strongly-interacting atoms (2020)

    Mitchell, Morgan W. (ICFO)

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    Entanglement of 15 trillion hot, strongly-interacting atoms

    Quantum entanglement is a process by which microscopic objects like electrons or atoms lose their individuality to become better coordinated with each other.  Entanglement is at the heart of quantum technologies that promise large advances in computing, communications and sensing, for example detecting gravitational waves. Entanglement is also thought to play an important role in macroscopic quantum phenomena such as superconductivity.

    Entangled states are famously fragile: in most cases even a tiny disturbance will undo the entanglement. For this reason, current quantum technologies take great pains to isolate the microscopic systems they work with, and typically operate at temperatures close to absolute zero. Here, in contrast, we heated a collection of atoms to 450 Kelvin, millions of times hotter than most atoms used for quantum technology. Moreover, the individual atoms were anything but isolated; they collided with each other every few microseconds, and each collision set their electrons spinning in random directions.

    We then used a laser to monitor the magnetization of this hot, chaotic gas. The magnetization is caused by the spinning electrons in the atoms, and provides a way to study the effect of the collisions and to detect entanglement. What we observed was an enormous number of entangled atoms – about 100 times more than ever before observed.  We also saw that the entanglement is non-local – it involves atoms that are not close to each other. Between any two entangled atoms there are thousands of other atoms, many of which are entangled with still other atoms, in a giant, hot and messy entangled state.

  • Developing kidney organoids to reveal how the coronavirus ravages the body (2020)

    Montserrat Pulido, Núria (IBEC)

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    Developing kidney organoids to reveal how the coronavirus ravages the body

    The generation of organoids is one of the biggest scientific advances in regenerative medicine. Here by exposing human pluripotent stem cells into inductive signals mirroring those found during embryonic kidney development I lead my team to derive mini-kidneys which upon single cell profiling showed to contain multiple cell clusters capturing important features of the human developing kidney. Upon extensive characterization we aimed to understand how SARS-Co-V2 interacts and infects human kidney cells. Our collaborative work also exploited vascular organoids to explore these questions. Moreover, we could validate a therapy able to reduce substantially viral load in both kidney and vascular organoids.

    This international collaboration led to more than 250 press communications (including TV, radio and web), being recently awarded by the ATRESMEDIA group and Fundación AXA with the award “Constants and Vitals” as the Best biomedical publication of 2020. Our collaboration with Professor Josef Penninger (Director of Life Science Institute at University British Columbia in Vancouver and IMBA in Vienna) and Professor Ali Mirazimi (Karolinska Institutet, Sweden) has also materialized in the obtention of different grants aiming to exploit organoid technology to target SARS-CoV-2-cell interactions, including ISCIII, IMI-H2020 and Fundación BBVA calls during 2020. 

     

  • A group of superior stem cells resists aging and maintains regeneration (2020)

    Muñoz-Cánoves, Pura (UPF)

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    A group of superior stem cells resists aging and maintains regeneration

    Skeletal muscle regeneration depends on a muscle stem cell population (satellite cells) in a dormant or quiescent state, a situation that can be triggered by damage or stress to form new muscle fibres and expand in new stem cells. The regenerative functions of these stem cells are known to decline with ageing.

    In this work we have identified a physiological mechanism that maintains the regenerative capacity of muscle stem cells, and surprisingly resists the passage of time far more than expected, until geriatric age. 

    Our in vivo experiments showed that all muscle stem cells, despite being quiescent, are not equal, identifying a subgroup of muscle stem cells that maintains its regenerative capacity over time, declining only at geriatric age. Our results have shown that this subgroup of quiescent stem cells has a greater regenerative capacity through the activation of the FoxO signalling pathway (previously associated with longevity), which maintains the expression of a youthful gene programme throughout life; however, at geriatric age, FoxO activation in this subgroup of cells is lost, causing their loss of functionality.

    The physiological mechanism maintaining the regenerative capacity of muscle stem cells over aging provides a novel approach for rejuvenating interventions. Compounds modulating this mechanism may rejuvenate aged muscle stem cells, opening the way to improve the health of elderly people who are debilitated by the loss of muscle mass. It may also be beneficial for recovering muscle mass loss in neuromuscular diseases, infectious or inflammatory diseases or cachexia associated to cancer.

     

  • Distal but functional: new tools for computational enzyme design (2020)

    Osuna Oliveras, Sílvia (UdG)

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    Distal but functional: new tools for computational enzyme design

    Enzyme Design: Enzymes are biomolecules capable of speeding the chemical reactions that take place in our body by many orders of magnitude, making them compatible with life. They are considered the most efficient catalysts known on Earth. Unfortunately, natural enzymes are not well suited for the industrial demands. Enzyme design aims to solve this limitation by introducing changes (i.e. mutations) in the natural enzyme sequence. 

    One of the most successful strategies for designing new enzymes for industrially-relevant reactions and conditions is experimental laboratory evolution. Although highly powerful, it has also a high economical cost associated, which hampers the extensive application of enzymes in industry. Computational enzyme design has the potential of predicting the set of specific changes required for novel enzymatic function, but so far none of the available strategies has been able to provide new enzymes with efficiencies rivaling those of natural and laboratory engineered enzymes. 

    Predicting distal functional mutations: The mutations introduced in many laboratory evolution experiments are often located all around the enzyme structure, which contrasts with computational enzyme design that reduces the problem into alterations in the region where the reaction happens (also called the active site). 

    How can we rationally predict distal activity-enhancing mutations? Given the large number of possible positions to mutate in natural enzymes, the computational prediction of such distal mutations impacting function has been proven to be extremely challenging. We have developed new computational tools that allow, for the first time, the prediction of mutations in the enzyme active site, but also at positions located distal from where the reaction occurs. This has been achieved by accurately considering the enzyme ability to adopt multiple conformations key for their enzymatic function.

  • FATal ATTRACTION: mammalian lipid droplets attract and kill intracellular pathogens (2020)

    Pol, Albert (IDIBAPS)

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    FATal ATTRACTION: mammalian lipid droplets attract and kill intracellular pathogens

    Background: In all eukaryotic cells, lipid droplets (LDs) store and supply essential lipids to produce signaling molecules, membrane building blocks, and metabolic energy. Common parasites (e.g. trypanosomes and Plasmodium falciparum), bacteria (e.g. mycobacteria and Chlamydia), and viruses (e.g. hepatitis C and dengue) induce and target LDs during their life cycles. The current view is that LDs support infection, providing microorganisms with substrates for effective growth. Rationale: Successful innate defense is critical for survival, and host species have efficiently co-evolved with pathogens to develop a plethora of immune responses. Multiple cues, including cellular stress and danger-associated molecular patterns such as lipopolysaccharide (LPS), induce LD formation. Thus, LD localization and dynamics may potentially be advantageous for organizing an intracellular host defense. Here, we have investigated the possibility that mammalian LDs have a direct and regulated role in innate immunity. Results: We show that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is upregulated during polymicrobial sepsis and by LPS. In response to infection, multiple host defense proteins, including interferon-inducible GTPases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD–bacterial contacts. Conclusions: We demonstrate that LDs comprise a first line intracellular defense. They act as a molecular switch in innate immunity, responding to danger signals by both reprogramming cell metabolism and eliciting protein-mediated antimicrobial mechanisms. In view of the widespread resistance to current antibiotics, this study helps decipher molecular mechanisms involved in antimicrobial defense that could be exploited for development of new anti-infective agents.