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

  • Liquid biopsy of cerebrospinal fluid for less invasive and more effective characterization of brain tumors (2015)

    Seoane Suárez, Joan (VHIO)

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    Liquid biopsy of cerebrospinal fluid for less invasive and more effective characterization of brain tumors

    In November 2015, Dr. Joan Seoane's group at the Vall d’Hebron Institute of Oncology (VHIO) published a study in Nature Communications proposing that the cerebrospinal fluid could be used as a liquid biopsy for the early diagnosis, prognosis, therapeutic management and tracking of brain cancer.

     

    The identification of each and every tumor type along with each respective individual molecular makeup is critical in tackling cancer with greater precision. Moreover, the study of how the tumor complexity evolves with time is crucial for the correct treatment of cancer. To date, the analysis of brain tumors has consisted of a biopsy or surgical sampling. Such approaches suppose risk per se and do not necessarily facilitate access to a representative part of the tumor. A new technique, liquid biopsy, has been recently and successfully developed which detects a tumor's specific mutations by means of the analysis of circulating tumor cell-free DNA. 

     

    The liquid biopsy 'policing' of cancer is not only facilitating a more precise treatment selection for each individual patient, but could also help us to be steps ahead of the cancer's next move. Compared to traditional tissue biopsy, it is a much less invasive technique, and represents a significant step forward towards a better detection of cancer mutations, tracking the evolution of the disease, as well as predicting the response to therapy. 

     

    Joan Seoane’s group has discovered that the cerebrospinal fluid is highly enriched in circulating tumor DNA and allows for the characterization of brain tumors. The cerebrospinal fluid flows through the brain parenchyma and the spinal cord and can be sampled by a lumbar puncture (similar to an epidural puncture). The cerebrospinal fluid liquid biopsy opens a novel, pioneering line of research into biomarkers that enable to monitor the progress of the disease and ultimately help to evaluate the effect of treatment and drug effectiveness as the cancer progresses.  

  • Pulsating news of 2015 (2015)

    Torres, Diego F. (CSIC - ICE)

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    Pulsating news of 2015

    Pulsars, being even more massive than the Sun, are very dense neutron stars that are the size of a city. Like lighthouses for the universe, emit radio to gamma-ray waves when they rotate up to hundreds of times per second. This year has been quite busy for pulsar research at ICREA.

    We found the most energetic pulsed photons from a pulsar to date, at TeV energies, and produced the most precise measurement of a pulsar nebula along several orders of magnitude in energy, with the MAGIC telescopes. We worked on detailed theoretical models for the latter emission. We witnessed the first pulsar discovered in another galaxy, as well as orbitally recurrent flaring in a pulsar binary, with Fermi-LAT. Transitional pulsars (which we discovered in 2013) are gamma-ray sources depending on the state they live, and we developed a propeller model that explains how.

    In a series of five theoretical papers published in Monthly Notices of the Royal Astronomical Society this year, we examined synchro-curvature radiation as a mechanism for gamma-ray emission in pulsars. We found that a relatively simple model can reproduce the spectra of practically all gamma-ray pulsars detected by the Fermi-LAT satellite, and that significant correlations arise for the model parameters that can be used to predict the gamma-ray brightness. Fig. 1 below is the main result of this research.

    Magnetars, among pulsars, usually possess very powerful magnetic fields. In 2013, we announced the discovery of a magnetar exceptionally close to the supermassive black hole at the center of the Galaxy. At a distance of 0.3 light years, this magnetar is by far the closest neutron star to a supermassive black hole ever discovered and is likely in its gravitational grip, see Fig. 2. We monitored the magnetar with X-ray satellites since, and this year we revealed that its brightness is dropping more slowly than any other previously observed, and its surface is hotter than expected. We considered starquakes and the bombardment of the surface of the magnetar by charged particles trapped in twisted bundles of magnetic fields above the surface as a way to provide heating, but the mystery still persists.

     

  • The forces that stick cells together (2015)

    Trepat, Xavier (IBEC)
    Guimerà Manrique, Roger (URV)

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    The forces that stick cells together

    Communication between cells is key to the coordinated functioning of organs, and a breakdown in communication is one of the characteristic features of cancer and chronic inflammatory diseases. Traditionally, such loss of communication between cells had been understood to result from purely biochemical factors, such as growth factors and chemokines. Recently, however, this traditional view has been challenged; physics of communication between cells is as important as the chemistry behind it.

    In this study, Roger Guimerà and Xavier Trepat – together withcolleagues at the Technical University of Catalonia (UPC) and the Rovira i Virgili University (URV) – combined molecular biology, nanotechnology and mathematical models to identify the molecules involved in the physical communication between cells. We developed technologies to map in parallel the main physical properties that govern tissue dynamics, including cellular velocities and deformations, as well as inter-, intra-, and extra-cellular forces. We used these tools to study epithelial dynamics while systematically knocking down the main proteins that comprise the intercellular adhesome.

    Global analysis of our data challenged several aspects of the current wisdom in the field. Firstly, we showed that force transmission at cell-cell junctions is not solely mediated by adherens junctions but also by proteins from tight junctions, desmosomes and gap junctions. Secondly, we established that P-cadherin (rather than E-cadherin) controls how much tension is supported by a cell-cell junction. E-cadherin, by contrast, controls how fast tension builds up. Finally, we demonstrated that simple models based on measured concentrations of cadherins and catenins are able to predict intercellular forces with high statistical significance.

  • Climate treaty: Pricing would limit carbon rebound (2015)

    van den Bergh, Jeroen (UAB)

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    Climate treaty: Pricing would limit carbon rebound

    This commentary was written as an advice to the negotations for a climate agreement at the COP21 climate summit in Paris (30 November - 13 December 2015). It raised attention for a neglected issue, namely carbon rebound of climate strategies in the absence of an adequate climate treaty. Energy rebound denotes that saving energy through technological improvements or behavioral changes triggers indirect, additional energy use. Various mechanisms contribute to this: e.g., improvements in energy efficiency make associated energy services cheaper which increases their consumption; saving energy means often saving money which is then spent on other energy-using goods or services; and more energy-efficient technologies diffuse easily to new types of uses or sectors.

    Unilateral national climate policies are not strict enough to control carbon rebound — a side effect of some energy conservation strategies that undercuts net carbon savings. I suggest that a global agreement on variable carbon pricing at the forthcoming climate summit in Paris would reap considerable rebound-related benefits.

    Economy-wide studies indicate that overall carbon rebound is at least 50%, depending on the country (J. Dimitropoulos Energy Policy 35, 6354–6363; 2007). Despite this, the effects of rebound have been largely ignored by the Intergovernmental Panel on Climate Change and at United Nations climate meetings.

    Technical standards do not control rebound effectively: they cover only a small subset of products. For example, when the European Union began phasing out incandescent light bulbs in 2009, light-emitting diodes became so widespread that any energy savings were reduced.

    The most effective way to discourage rebound is through carbon pricing, a policy that underpins all potential energy saving decisions. Any rebound tendency would elicit a higher carbon price under a cap-and-trade permit scheme. A carbon tax would require frequent adjustment to achieve the same outcome. This would be difficult politically, especially in the form of nationally distinct taxes.

  • Ultrafast Graphene (2015)

    van Hulst, Niek F. (ICFO)
    Koppens, Frank (ICFO)

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    Ultrafast Graphene

    The efficient conversion of light into electricity plays a crucial role in many technologies, ranging from cameras to solar cells. It also forms an essential step in data communication applications, since it allows for information carried by light to be converted into electrical information that can be processed in electrical circuits. Graphene is an excellent material for ultrafast conversion of light to electrical signals, but so far it is not known how fast graphene responds to ultrashort flashes of light.

    Researchers at ICFO, in collaboration with MIT & UC Riverside, have developed a graphene-based photodetector capable of converting absorbed light into an electrical voltage at ultrafast timescales. The new device combines the ICFO expertise in both ultrafast pulse shaping and graphene electronics. Finally, facilitated by graphene’s nonlinear photo-thermoelectric response, these elements enabled the observation of femtosecond photodetection response times.

    The ultrafast creation of a photovoltage in graphene is possible due to the extremely fast and efficient interaction between all conduction band carriers in graphene. This interaction leads to a rapid creation of an electron distribution with an elevated electron temperature. Thus, the energy absorbed from light is efficiently and rapidly converted into electron heat. Next, the electron heat is converted into a voltage at the interface of two graphene regions with different doping. This photo-thermoelectric effect turns out to occur almost instantaneously, thus enabling the ultrafast conversion of absorbed light into electrical signals and opening new pathways towards ultra-fast optoelectronic conversion. Clearly, graphene photodetectors show fascinating performances addressing a wide range of applications.

  • A transcription factor that promotes the formation of tumours in the colon (2014)

    Batlle Gómez, Eduard (IRB Barcelona)

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    A transcription factor that promotes the formation of tumours in the colon

    Constitutive activation of WNT signalling in the intestinal epithelium by mutations in genes encoding pathway components such as APC or beta-catenin leads to the formation of adenomas. These precancerous lesions are prevalent in the population and represent the substrate from which colorectal cancer (CRC) develops. An alternative pathway leading to the formation of intestinal tumours is initiated by mutational inactivation of the bone morphogenetic protein (BMP) signalling pathway. Individuals with germline mutations in BMP pathway components such as BMPRI or SMAD4 develop hamartomatous polyps, benign outgrowths of the epithelium that confer high risk of CRC. In addition, genome wide association studies of CRC have identified about 30 common low-risk susceptibility variants, four of which map in genomic regions located near the locus encoding BMP pathway components SMAD7, GREM1, BMP4 and BMP7. In this work, we screen for genes required for maintaining the tumour stem cell phenotype and identify the zinc-finger transcription factor GATA6 as a key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of bona-fide stem cell maker LGR5 in adenoma stem cells whereas it restricts BMP signaling to differentiated tumour cells. We show that the genetic deletion of Gata6 from mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumour stem cells. In human tumours, GATA6 competes with beta-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been linked to increased susceptibility to development of CRC. Therefore, GATA6 creates an environment permissive for CRC initiation by lowering the threshold of BMP signalling required for tumour stem cell expansion.

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