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

  • Random diffusivity in cell membranes and connection with receptor function  (2015)

    García Parajo, Maria F. (ICFO)
    Lewenstein, Maciej Andrzej (ICFO)

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    Random diffusivity in cell membranes and connection with receptor function 

    Fundamental biological processes are regulated by molecular transport. The quantification of molecular diffusivity has fundamental importance in studying the function of biological molecules in living cells. This is because mobility is often affected by interactions between the molecule under study and its surroundings, reporting not only on the occurrence of interactions but, more importantly, it allows inferring on its functional role for cell response. One of the most powerful experimental approaches to study the mobility of individual molecules and interactions with the environment in living cells is single particle tracking (SPT).

    Although many cellular components exhibit anomalous diffusion, only recently has this sub-diffusive motion been associated with nonergodic behavior. Nonergodic dynamics refers to the difference between the properties of a particle in time and an ensemble of particles. These findings have stimulated new questions for their implications in statistical mechanics and cell biology. Is nonergodicity a common strategy shared by living systems? Which physical mechanisms generate it? What are its implications for biological function?

    Using SPT we demonstrated that the motion of the pathogen recognition receptor DC-SIGN exhibits nonergodic subdiffusion on living-cell membranes.  Indeed, the receptor undergoes changes of diffusivity, consistent with the current view of the cell membrane as a highly dynamic and diverse environment. Our experimental data could be fully recapitulated using a simple theoretical model based on ordinary random walks that change in space in time. Importantly, by studying different receptor mutants, we further correlated receptor motion to its molecular structure, thus establishing a strong link between nonergodicity and biological function.

    These results underscore the role of disorder in cell membranes and its connection with function regulation. Because of its generality, this approach offers a framework to interpret anomalous transport in other complex media where dynamic heterogeneity might play a major role, such as those found, e.g., in soft condensed matter, geology, and ecology.

  • A new tool to Predict Metastasis of Breast Cancer to the Bone (2015)

    Gomis, Roger (IRB Barcelona)

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    A new tool to Predict Metastasis of Breast Cancer to the Bone

    Bone metastasis is the only type of metastasis that can be controlled, but not cured, by drugs. Treatment is only given once the metastasis has been identified, which is normally too late. Preliminary clinical studies indicate that the same drugs used to treat metastasis could also be used to prevent it, and identifying those patients at risk of developing bone metastasis is therefore very important.

    About one million new cases of breast cancer are diagnosed each year. Preventive treatment for bone metastasis can have unwanted side effects and comes at a high cost, making a broad administration of the drugs an unviable option, even less so considering only 15-20% of patients are likely to develop metastasis over time. In order to implement a well-designed clinical trial, it is needed to know which patients may benefit and which ones will not.

    Experiments in the Growth Control and Cancer Metastasis Laboratory at the Institute for Research in Biomedicine (IRB Barcelona) led by the ICREA Research Professor Roger Gomis, have focused on the analysis of estrogen-receptor-positive breast tumors since they specifically tend to metastasize to the bone, and represent 80% of all breast cancers. The results indicate that the gene MAF triggers a set of functions in the cell that allow metastasis to take place in the bone.

    The researchers analyzed more than 900 clinical samples of primary breast tumors. In tumors in which the MAF gene is altered, the risk of metastasis to the bone is 14 times higher than in those in which it is unaltered. Thus, the biomarker reliably predicts metastasis to the bone. Studying whether it is highly expressed in breast cancer patients to determine whether this also happens in a clinical setting is an important next step. It could improve the quality of life of these patients and the way clinicians manage their cancer. And this is exactly what we the researchers are doing in collaboration with other institutions.

  • HEAR-EU: Computational models of cochlear implants (2015)

    González Ballester, Miguel A. (UPF)

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    HEAR-EU: Computational models of cochlear implants

    A cochlear implant (also known as bionic ear) is a device that completely replaces the hearing system by implantable electronics, a remarkable step towards cyborg technology. It leads to hearing restoration in patients with moderate to severe hearing loss, by direct auditory nerve stimulation. 

    Electrical stimulation of the brain has been extremely successful to date: important examples include cochlear implants and deep brain stimulation (DBS), which are two extremely effective and safe techniques. However, in both cases, the extent of the electrical stimulation and its effect on the brain is not well known. This, combined with the lack of pre-operative measures that predict the outcomes after implantation, results in high variability in the patient’s response. We argue that this variability could be reduced by the use of predictive computational models.

    The aim of the HEAR-EU project (FP7 project coordinated by ICREA Professor Miguel A. González Ballester) is to develop computational tools to improve the prediction of cochlear implantation surgery and, consequently, to enable the improvement of hearing implant designs. As part of this project, in this work we present a framework that combines the use of highly detailed imaging techniques, finite element methods, flexible CAD structures, and a dynamic model of the nerve fibers, thus improving our knowledge of the nervous system–electrode interface.

    We apply our framework to the case of cochlear implants, showing how we can predict nerve response for patients with both intact and degenerated nerve fibers. Then, using the predicted response, we calculate a metric for the usefulness of the stimulation protocol and use this information to rerun the simulations with better parameters, thus leading to optimized patient-specific treatment.

    This work was carried out in collaboration with NASA Ames Research Center in California.

  • Diet, Environment and Respiratory Irritants in the Lower Palaeolithic (2015)

    Hardy, Karen (UAB)

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    Diet, Environment and Respiratory Irritants in the Lower Palaeolithic

    Reconstructing detailed aspects of the lives of Lower Palaeolithic hominins, who lived during the Middle Pleistocene, is challenging due to the restricted nature of the surviving evidence, predominantly animal bones and stone tools. But hominins, just like humans, needed plant foods in order to survive and reproduce. The site of Qesem Cave, Israel, which was inhabited between 420,000-200,000 years ago, has evidence for a wealth of innovative features including the earliest clear evidence worldwide for controlled use of fire.  Analysis of remains embedded in samples of dental calculus from the hominins who lived here found evidence for a range of inhaled and ingested materials. These finds offer an insight into the environment in and around the cave, as inhaled pollen grains from pine trees indicate a forested environment, while micro-charcoal suggests smoke inhalation may have been a problem inside the cave.  Plant fibres and a phytolith may be evidence of oral hygiene activities or of using the teeth to work raw materials. Starch granules and chemical compounds provide a direct link to ingested plant food items, most specifically, the presence of plants containing the essential linoleic and linolenic polyunsaturated fatty acids. Together, these results represent a significant breakthrough towards a better understanding of Middle Pleistocene dietary breadth and highlight some of the challenges facing the adoption of the habitual use of fire for cooking by the Qesem Cave hominins, as well as offering new information on the paleoenvironment surrounding the cave, and new insights into palaeolithic ecological knowledge and technological adaptability.

  • ‘DNA spellchecker’ means that our genes aren’t all equally likely to mutate and cause cancer (2015)

    Lehner, Ben (CRG)

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    ‘DNA spellchecker’ means that our genes aren’t all equally likely to mutate and cause cancer

    Copying the large book that it is our genome without mistakes every time a cell divides is a difficult job. Luckily, our cells are well-equipped to proof-read and repair DNA mistakes. This study showed that mistakes in different parts of our genome are not equally well corrected.  This means that some of our genes are more likely to mutate during our lifetimes and so contribute to disease than others.

    The scientists analysed 17 million ‘single nucleotide variants’ – mutations in just one nucleotide (letter) of the DNA sequence – by examining 650 human tumours from different tissues. These were ‘somatic’ mutations, meaning they are not inherited from parents or passed down to children, but accumulate in our bodies as we age. Such somatic mutations are the main cause of cancer. Many result from mutagens, such as tobacco smoke or ultraviolet radiation, and others come from naturally occurring mistakes in copying DNA as our tissues renew.

    Ben Lehner and his team had previously described that somatic mutations are much more likely in some parts of the human genome, thus damaging genes that may cause cancer. In a new paper they show that this is because genetic mistakes are better repaired in some parts of the genome than in others. This variation was generated by a particular DNA repair mechanism called “mismatch repair” – a sort of a spellchecker that helps fix the errors in the genome after copying. The data showed that the efficiency of this ‘DNA spellchecker’ varies depending on the region of the genome, with some parts of chromosomes getting more attention than others. The study illustrates how data from medical sequencing projects can answer basic questions about how cells work.

  • Nanopaper as an Optical Sensing Platform (2015)

    Merkoçi, Arben (ICN2)

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    Nanopaper as an Optical Sensing Platform

    Cellulose is simple, naturally abundant and low cost. However, cellulose fibres ranging at the nanoscale exhibit extraordinary properties such as flexibility, high crystallinity, biodegradability and optical transparency. The nanomaterial can be extracted from plant cellulose pulp or synthetized by non-pathogenic bacteria. Nanocellulose is under active research to develop a myriad of applications including filtration, wound dressing, pollution removal approaches or flexible and transparent electronics, whereas it has been scarcely explored for optical (bio)sensing applications.

    The team led by Prof. Merkoçi seeks to design, fabricate, and test simple, disposable and versatile sensing platforms based on this material. They designed different bacterial cellulose nanopaper based optical sensing platforms. In the article, it is described how the material can be tuned to exhibit plasmonic or photoluminescent properties that can be exploited for sensing applications. Specifically, they have prepared two types of plasmonic nanopaper and two types of photoluminescent nanopaper using different optically active nanomaterials.

    The researchers took advantage of the optical transparency, porosity, hydrophilicity, and amenability to chemical modification of the material. The bacterial cellulose employed throughout this research was obtained using a bottom-up approach and it is shown that it can be easily turned into useful devices for sensing applications using wax printing or simple punch tools. They also demonstrate how these novel sensing platforms can be modulated to detect biologically relevant analytes such as cyanide and pathogens.

    According to the authors, this class of platforms will prove valuable for displaying analytical information in diverse fields such as diagnostics, environmental monitoring and food safety. Moreover, since bacterial cellulose is flexible, lightweight, biocompatible and biodegradable, the proposed composites could be used as wearable optical sensors and could even be integrated into novel theranostic devices. Paper-based sensors might be exploited in medicine, detection of explosives or hazardous compounds and environmental studies.

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