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

  • Sweet mysteries of nature: computer simulations unravel how carbohydrates form (2011)

    Rovira Virgili, Carme (PCB)

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    Sweet mysteries of nature: computer simulations unravel how carbohydrates form

    Fifty per cent of our daily calorie intake comes from carbohydrates, our "biological fuel". Moreover, carbohydrates influence cell-to-cell communication, the functioning of the immune system, the ability of various infectious agents to make us sick, and the progression of cancer.

    One of the most important reactions in the metabolism of carbohydrates is the formation of the glycosidic bond, i.e. the covalent linkage between simple monosacharides (monomers) to build polysaccharides such as glucogen, starch or celulose (polymers).

    Most glycosidic bonds are synthesized in nature from sugars that are activated by a cofactor (mostly, a nucleotide). The enzymes responsible for this action are glycosyltransferases (GTs), which form the glycosidic bond by transferring a sugar molecule from a donor molecule (an activated sugar) to an acceptor molecule (typically another sugar). These enzymes can operate with retention or inversion of the configuration of the carbon atom of the glycosidic bond they form. The mechanism of inverting GTs is well known, but the mechanism of retaining GTs has remained one of the most puzzling aspects in the field of glycobiology.

    It had been proposed that the enzyme helps the reaction by binding to the donor molecule. Still, the lack of clear experimental evidence led scientists to think of an extremely unusual "front-face" type mechanism, in which the reaction takes place on a single "face" of the sugar. This mechanism has been surrounded by much controversy, since in principle it implies that two covalent bonds are forming and breaking, respectively, in the same region of space.

    By means of ab initio molecular dynamics techniques and the use supercomputers (BSC), the PCB researchers demonstrated that the "front-face" type mechanism is feasible thanks to the formation of a positively-charged species (a carbocation) with an extremely short half-life that moves quickly from the donor to the acceptor.

    The modelled enzyme is glycosyltransferase trehalose-6-phosphate synthase (OtsA), which participates in the final synthesis of trehalose, a disaccharide of great importance in nature. Given their absence in mammalian biology, trehalose synthesising and processing enzymes offer attractive inhibition targets.

    Glycosyltransferases are responsible for the structure of many carbohydrates and, therefore, the knowledge of their mechanism of action will help to modify their function, thereby improving the synthesis of known carbohydrates and new structures. It will also contribute to th

  • The cell dance: a minuet or a mosh? (2011)

    Trepat, Xavier (IBEC)

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    The cell dance: a minuet or a mosh?

    The physical forces that guide how cells migrate--how they manage to get from place to place in a coordinated fashion inside the living body-- are poorly understood. Our group devised, for the first time, a technique to measure these forces during collective cellular migration. Using this technique we reached the surprising conclusion that the cells fight it out, each pushing and pulling on its neighbors in a chaotic dance, yet together moving cooperatively toward their intended direction.

    Until now it was known that cells could follow gradients of soluble chemical cues, called morphogens, which help to direct tissue development, or they could follow physical cues, such as adhesion to their surroundings. Fundamental studies of these and other mechanisms of cellular migration have focused on dissecting cell behavior into ever smaller increments, trying to get to the molecular roots of how migration occurs. In contrast, we decided to work at a higher level--the group level--and focused on the forces that cells exert upon their immediate neighbors.

    Collective cellular migrations are necessary for multicellular life; for example, in order for cells to form the embryo, cells must move collectively. Or in the healing of a wound, cells must migrate collectively to fill the wound gap. But the migration process is also dangerous in situations such as cancer, when malignant cells, or clumps of cells, can migrate to distant sites to invade other tissues or form new tumors. Understanding how and why collective cellular migration happens may lead to ways to control or interrupt diseases that involve abnormal cell migration. To this aim, we developped a measurement technology called Monolayer Stress Microscopy, which allows us to visualize the nanoscale mechanical forces exerted at the junctions where individual cells are connected.

    We initially thought that as cells are moving--say, to close a wound--the underlying forces would be synchronized and smoothly changing so as to vary coherently across the crowd of cells, as in a minuet. Instead, we found the forces to vary tremendously, occurring in huge peaks and valleys across the monolayer. So the forces are not smooth and orderly at all; they are more like those in a `mosh pit'--organized chaos with pushing and pulling in all directions at once, but collectively giving rise to motion in a given direction. We named this new phenomenon "plithotaxis," a term derived from Greek "plithos" suggestive of throng, swarm or crowd.

  • Antennas for Light (2011)

    van Hulst, Niek F. (ICFO)

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    Antennas for Light

    Antennas are all around in our modern wireless society: they are the front-ends in satellites, cell-phones, laptops, etc., that establish the communication by sending and receiving signals, typically MHz-GHz. Characteristic for any town is the chaotic forest of TV antennas covering roofs: metal bar constructions forming sub-wavelength structures, optimized to receive (or send) directional electro-magnetic fields with the wavelengths of the TV/radio signal. Can the proven antenna technology be scaled up towards the optical domain, i.e. from some 100 MHz towards typically a million times higher frequency of around 500 THz? Inevitably, this implies scaling down to a million times smaller structures, with dimensions of typically 100 nm, requiring nanofabrication accuracy down to a few nm. Moreover metals at optical frequencies are far from ideal, very dispersive and usually lossy. These are definite challenges in scaling antennas towards visible light, but the promise is clear: light, despite its submicron wavelength, is conventionally guided by rather bulky elements, such as lenses, mirrors and optical fibres. Optical antennas convert freely propagating optical radiation into localized energy, and vice versa. They enable the control and manipulation of optical fields at the nanometre scale, comparable to the scale of electronic integrated circuitry, and hold promise for enhancing the performance and efficiency of photodetection, light emission and sensing. Indeed this has motivated the exploration of modern nanofabrication methods, such as focussed electron and ion beams, to fabricate nanostructures and antennas with optical resonances. Although many of the properties and parameters of optical antennas are similar to their radiowave and microwave counterparts, they have important differences resulting from their small size and the resonant properties of metal nanostructures. The review in Nature Photonics, by Lukas Novotny (Inst. Optics, Rochester, USA) and Niek van Hulst (ICFO, Barcelona), describes recent developments in the field, discusses the potential applications and identifies the future challenges and opportunities.

  • Feel the heat? Choose your 3' end (2011)

    Vilardell Trench, Josep (CSIC - IBMB)

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    Feel the heat? Choose your 3' end

    (The following has been taken from Science "Editor's Choice" Sept 30, 2011, Vol 333, p. 1802; written by Guy Riddihough)
    Many eukaryotic genes contain noncoding sequences--introns--that must be removed before translation. The 5' slice site is determined by base-pairing interactions with the U1 snRNA of the spliceosome, a large ribonuclear-protein complex that catalyses the removal of introns. How the spliceosome finds the other (3') end of the intron--nominally marked by no more than the dinucleotide sequence AG--is less clear.
    While studying a budding yeast gene, Meyer et al. found that the potential destabilization of an RNA secondary structure downstream othe intron branch point (a sequence critical in the splicing reaction) had an adverse effect on splicing. Analyzing the RNA folding potential of sequences between the intron branch point and the 3' splice site for 282 yeast introns revealed that a substantial fraction had the potential
    to form secondary structures. In vivo, the RNA secondary structure functioned to bring distant 3' splice sites within a specific distance window, which is neither too close to nor too far from the intron branch point, thus allowing effec- tive 3' splicing to occur and implying that the spliceosome has a limited "reach." For another gene, choice of the 3' splice site is influenced by temperature, which is sensed through the thermal stability of the RNA secondary structure, implying that such structures can function in a regulatory capacity.

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