Spain
Spain

Time filter

Source Type

News Article | December 2, 2016
Site: phys.org

Since it is based on a different principle, this method complements conventional tools and allows going forward in the path of rational drug design. ICREA researcher Xavier Barril, from the Faculty of Pharmacy and Food Sciences and The Institute of Biomedicine of the University of Barcelona (IBUB), has led this project, which has the participation of professor Francesc Xavier Luque and PhD student Sergio Ruiz Carmona, members of the same Faculty. The improvement on efficiency and effectiveness in the discovery of drugs is a key target in pharmaceutical research. In this process, the target are molecules that can be added to a target protein and modify its behavior according to clinical needs. "All current methods to predict if a molecule will join the wished protein are based on affinity, that is, in the complex's thermodynamic stability. What we are proving is that molecules have to create complexes that are structurally stable, and that it is possible to distinguish between active and inactive by looking at what specific interactions are hard to break", says Professor Xavier Barril. This approach has been applied in software that identifies molecules with more possibilities to join the targeted protein. "The method allows selecting molecules that can be starting points to create new drugs", says Barril. "Moreover, -he continues- the process is complementary with existing methods and allows multiplying five times the efficiency of the current processes with lower computational prices. We are actually using it successfully in several projects in the field of cancer and infectious diseases, among others". A new vision for the protein-ligand drugs This work introduces a new way of thinking regarding the ligand-protein interaction. "We don't look at the balancing situation, where two molecules make the best possible interactions, but we also think how the complex will break, which the breaking points are and how we can improve the drug to make it more resistant to separation. Now we have to focus on this phenomenon to understand it better and see if by creating more complex models we can still improve our predictions", says the researcher. The team of the University of Barcelona is already using this method, which is open to all the scientific community. Explore further: New therapeutic target for diseases caused by lack of oxygen More information: Sergio Ruiz-Carmona et al. Dynamic undocking and the quasi-bound state as tools for drug discovery, Nature Chemistry (2016). DOI: 10.1038/nchem.2660


News Article | December 15, 2016
Site: www.eurekalert.org

Bits of wood recovered from a 1.2-million-year-old tooth found at an excavation site in northern Spain indicate that the ancient relatives of man may have use a kind of toothpick. Toothbrushes were not around yet, if the amount of hardened tartar build-up is anything to go by. An analysis of the tartar has now yielded the oldest known information about what our human ancestors ate and the quality of their diet. According to study leader Karen Hardy of the Catalan Institute for Research and Advanced Studies (ICREA) and the Universtat Autònoma de Barcelona, what they ate was consumed raw, and shows that 1.2 million years ago hominins did not yet know how to use fire to prepare food. The findings are published in Springer's journal The Science of Nature. The teeth investigated by Hardy's team come from one of the two oldest hominin remains yet to be found in Europe. The piece of jawbone found in 2007 at the Sima del Elefante excavation site in Spain's Atapeurca Mountains is between 1.1 million and 1.2 million years old. Sima del Elefante is part of several archaeological and palaeontological sites that together represent a history that is between 300,000 years and 1.2 million years old. Dental calculus or tartar, a form of hardened plaque, was found on all but one of the teeth examined. A minute sample of tartar from one of the teeth was removed using an ultrasonic scalar, and then analyzed to recover the microfossils trapped in it. These included several types of fibres, including tiny pieces of non-edible wood, plants and animal tissue. A scale from a butterfly's wing and a fragment of an insect leg was also detected. One of the two types of fungal spores recovered is similar to the modern day plant pathogen Alternaria, which is associated with asthma and hay fever. The wood fibres come from a groove at the bottom of the tooth, called the interproximal groove, which is thought to be caused by regular tooth picking. Previously, the oldest known example of this type of dental hygiene came from the remains of a much younger 49,000 year old Neanderthal. Some of the starch granules trapped in the tartar suggest the hominins may have eaten grass seeds. From the conifer pollen grains present, Hardy's team deducts that the hominin lived close to a forest. "It is plausible that these ancient grasses were ingested as food," says Hardy. "Grasses produce abundant seeds in a compact head, which may be conveniently chewed, especially before the seeds mature fully, dry out and scatter." According to Hardy, the intact nature of the starch granules and the uncharred fibres found show that the hominins did not yet know how to use fire with which to cook raw food. The teeth examined had been worn down and showed signs of heavy use that suggest the teeth were used to grip and chew raw materials. Hardy concludes, "Our evidence for the consumption of at least two different starchy plants, in addition to the direct evidence for consumption of meat and of plant-based raw materials suggests that this very early European hominin population had a detailed understanding of its surroundings and a broad diet." Reference: Hardy, K. et al. (2016). Diet and environment 1.2 million years ago revealed through analysis of dental calculus from Europe's oldest hominin at Sima del Elefante, Spain. The Science of Nature. DOI 10.1007/s00114-016-1420-x


News Article | January 20, 2016
Site: phys.org

Active in situ control of light at the nanoscale remains a challenge in modern physics and in nanophotonics in particular. A promising approach is to take advantage of the technological maturity of nanoelectromechanical systems (NEMS) and combine the technology with on-chip optics, but the integration of such small devices with optical fields remains difficult. In a recent work published in Nature Communications, ICFO researchers Dr. Antoine Reserbat-Plantey, Kevin G. Schadler, and Dr. Louis Gaudreau, led by ICREA Professors at ICFO Frank H. L. Koppens and Adrian Bachtold and ICFO Professor Darrick Chang, have presented a novel type of hybrid system consisting of an on-chip graphene NEMS suspended a few tens of nanometres above nitrogen-vacancy centres (NVCs), which are stable, single-photon emitters embedded in nanodiamonds. Their work has confirmed that graphene is an ideal platform for both nanophotonics and nanomechanics. For their study, the researchers fabricated such an original hybrid device for the first time. Due to its electromechanical properties, graphene NEMS can be actuated and deflected electrostatically over few tens of nanometres with modest voltages applied to a gate electrode. The graphene motion can thus be used to modulate the light emission by the NVC, while the emitted field can be used as a universal probe of the graphene position. The optomechanical coupling between the graphene displacement and the NVC emission is based on near-field dipole-dipole interactions. The researchers could see that the coupling strength increases strongly for shorter distances and is enhanced because of graphene's two-dimensional (2D) character and linear dispersion. These achievements hold promise for selective control of emitter arrays on-chip, optical spectroscopy of individual nano-objects, integrated optomechanical information processing, and opens new avenues toward quantum optomechanics. More information: Antoine Reserbat-Plantey et al. Electromechanical control of nitrogen-vacancy defect emission using graphene NEMS, Nature Communications (2016). DOI: 10.1038/ncomms10218


News Article | December 19, 2016
Site: www.prnewswire.co.uk

El Instituto de Oncología Vall d'Hebron acelera los ensayos clínicos del primer anticuerpo terapéutico de su clase para el cáncer BARCELONA, España y TORONTO, 19 de diciembre de 2016 /PRNewswire/ -- Mosaic Biomedicals SL anunció hoy una fusión con Northern Biologics Inc. que permitirá el desarrollo acelerado de MSC-1, un anticuerpo humanizado que se espera comenzar a utilizar en ensayos clínicos en varios tipos de tumor en 2017, con múltiples sitios previstos a lo largo de Europa y Norteamérica. MSC-1 es el primer anticuerpo de su clase con objetivo en el factor inhibidor de leucemia (LIF), una citoquina pleiotrópica que se sobreexpresa en ciertos tumores sólidos. LIF promueve la progresión del cáncer por regulación del microambiente tumoral, así como induciendo la auto-renovación en células iniciadoras del tumor. Iniciar el trabajo sobre el papel de LIF en la oncogénesis y el descubrimiento de MSC-1, fue realizado bajo la dirección de Joan Seoane, Ph.D., cofundador de Mosaic y director de investigación traslacional del Instituto de Oncología Vall d'Hebron (VHIO). Versant Ventures ha ampliado su compromiso de serie A con la empresa y Celgene Corp. ha ejercido una opción para adquirir ciertos derechos al programa MSC-1 bajo su acuerdo existente con Northern Biologics. Después de las operaciones, la financiación completa está en el lugar para el desarrollo clínico temprano de MSC-1, además de una cartera preclínica de anticuerpos terapéuticos. El Dr. Seoane, que se ha unido a la junta directiva de la compañía fusionada, comentó: "Esta fusión es una manera fantástica para el equipo de Mosaic Biomedicals de unir fuerzas con Northern y reunir el capital, conocimientos, talento y liderazgo internacional necesarios para desarrollar los anticuerpos terapéuticos más eficaces lo antes posible." "Con el apoyo de socios clave y la fuerza financiera para dar a MSC-1 la mayor posibilidad de éxito, este acuerdo representa una oportunidad sin precedentes para que Mosaic alcance su pleno potencial," añadió la Dra. Judit Anido, co-fundadora de Mosaic y miembro del equipo ejecutivo. El Dr. José Baselga, también co-fundador de Mosaic, será el presidente y asesor médico de la junta científica de la nueva compañía de fusión. Beneficio para los pacientes y un motor económico para la sociedad Mosaic se estableció por el Dr. Seoane de VHIO, un centro integral de cáncer dentro de la privilegiada ubicación del Hospital Universitario Vall d'Hebron. Investigadores y médicos-científicos de VHIO adoptan un modelo de investigación puramente traslacional, trabajando como equipos multidisciplinarios para acelerar y promover terapias personalizadas y dirigidas contra el cáncer. Mosaic es la primera empresa derivada de VHIO, en asociación con ICREA y el Instituto de Investigación Vall d'Hebron (VHIR). "La financiación pública proveniente del programa Retos de Colaboración, ENISA, CDTI y ERC´s PoC, entre otros, han sido esenciales en la creación de Mosaic, para traducir rápidamente el descubrimiento científico en beneficios para el paciente. La empresa también se convertirá en un motor económico para devolver valor a la sociedad que ha invertido en investigación del cáncer," dijo el Dr. Seoane y la Dra. Anido, que también agradecen el apoyo recibido del primer Business Angels y amigos que creyeron en el proyecto desde el principio y proporcionaron fondos para los pasos de configuración inicial. La posterior inversión de Versant y Caixa Capital Risc, estimuló más desarrollo de Mosaic Biomedicals y condujo a MSC-1 al borde de los ensayos clínicos. La fusión con Northern Biologics y nueva inversión significativa ha aumentado aún más las ambiciones del equipo y traerá el proyecto a una emocionante nueva etapa de desarrollo clínico. "Nada de esto hubiera sido posible sin el excelente trabajo en equipo - desde mi grupo de investigación en particular, trabajando diariamente en lo que realmente importa, es decir, empujando los límites en la ciencia del cáncer. Esta tremenda empresa, ahora apoyada por óptimas condiciones financieras y técnicas, nos permitirá continuar avanzando y mejorar en última instancia el tratamiento y la atención de un creciente número de pacientes con cáncer," dijo el Dr. Seoane. Acerca de Mosaic Biomedicals Mosaic Biomedicals es una empresa de Barcelona que desarrolla tratamientos personalizados contra el cáncer con un doble mecanismo de acción para eliminar las células madre cancerosas y reactivar el sistema inmune del tumor. Mosaic es una empresa derivada del Instituto de Oncología Vall d'Hebron, Institució Catalana de Recerca i Estudis Avançats (ICREA) y el Instituto de Investigación Vall d'Hebron (VHIR), respaldado por Versant Ventures, Caixa Capital Risc y varios inversores. Acerca de Northern Biologics Northern Biologics se lanzó en junio de 2014 por Blueline Bioscience, una incubadora de biotecnología canadiense respaldada por la firma de capital de riesgo Versant Ventures, en colaboración con la Universidad de Toronto y el University Health Network's Princess Margaret Cancer Centre. Con sede en el MaRS Discovery District de Toronto, la empresa está desarrollando una cartera de tratamientos basados en anticuerpos para oncología y fibrosis.


News Article | December 28, 2016
Site: www.medicalnewstoday.com

In spite of the many drugs available to treat breast cancer, resistance continues to be a problem. Based on the study of cell signalling networks, the cell signals that drugs alter when they reach their target molecule, an exhaustive in silico analysis of the pairing of 64 therapeutic agents used to treat breast cancer (half already in use and the other half in clinical testing phase) has allowed researchers at the Institute for Research in Biomedicine (IRB Barcelona) to identify 10 new and previously untested combinations that hold potential for the treatment of breast cancer. Seven of the 10 combinations tested in breast tumour cells in vitro have shown a high level of synergy (the joint effect is greater than the sum of the individual effects) and one of these combinations has been validated in mice. The results in mouse models indicate that the combination of raloxifene and cabozantinib, two drugs prescribed by oncologists, "dramatically" boost the anti-tumour effects of each of the two drugs, as the authors explain in Cancer Research, the journal that has published the results in its advanced online edition. Patrick Aloy, ICREA researcher and head of the Structural bioinformatics and network biology lab at IRB Barcelona, says, "we identify many more synergistic combinations in silico than combinatorial assays do until now with high-performance lab techniques, and we can provide experimental details. This implies that prior computational analyses give better results and are more reliable". The researchers point out that in 70% of the combinations tested, the joint effects of the two drugs is "much much greater" than the effect of each alone, and therefore the same effect could be achieved with a smaller dose. In this case, when scientists tested combined raloxifene and cabozantinib treatment in mice, they observed that the tumour shrank by 60%, while the individual effect of each drug merely prevented further tumour growth. Moreover, with the combination, a dose 3 and 25 times smaller, respectively, can be used compared to current treatments. "This in itself is very important because drugs are in fact toxic and are used to kill cells. If, by using a smaller dose, a greater - or even the same - chemotherapeutic effect is achieved, it is a significant advantage with respect to reducing the side effects experienced by patients," says Aloy. "Also, in principle, resistance would be avoided or delayed," he comments. In cancer treatment, including breast cancer, one of the problems faced by patients and oncologists is the onset of treatment resistance. Cancer cells become "insensitive" to the drugs that should kill them. Resistance arises because the cancer cell, via the development of random mutations, learns to evade the effect of the drug. In 15% of cases, alternative molecular signalling pathways are activated to allow the tumour cells to divide again or to evade programmed cell death. Combined therapy using two or more drugs emerges as a promising approach to tackle this kind of resistance. "Our analyses have allowed us to predict the signalling pathways that are inactivated by the joint action of two drugs," explains Samira Jaeger, postdoctoral fellows and first author of the study. The scientists validated at the molecular level that the molecules predicted in the in silico model were indeed inhibited. "By combining drugs, we aim to attack the tumour cell simultaneously from various flanks, thus making it more difficult for the cell to resist treatment, as the pathways that allow it to survive and proliferate will be knocked out the same time," she explains. Having validated the computational network model, the scientists have three research lines running. First, and with the aim to move towards clinical applications, they will test combined treatment with raloxifene and cabozantinib in tumours taken from patients and transplanted in mice. For this purpose, and as in the study just done, they will work in collaboration with ICREA researcher Angel R. Nebreda, a member of the Oncology Programme at IRB Barcelona. Second, with the same aim to find more effective treatments for breast cancer, the lab will focus on pairing an anti-tumour agent and a drug administered for other conditions, such as those used to treat diabetes and high blood pressure. Finally, Aloy's lab is fine-tuning an experimental method that will allow them to validate the combined therapies that show the greatest long-term efficiency in treating resistance. This study has been funded by the European Research Council (ERC Consolidator grant), the Ministry of Economy and Competitiveness and FEDER funds, a EU Marie Curie COFUND grant and the Generalitat de Catalunya. Article: Quantification of pathway crosstalk reveals novel synergistic drug combinations for breast cancer, Samira Jaeger, Ana Igea, Rodrigo Arroyo, Victor Alcalde, Begoña Canovas, Modesto Orozco, Angel R. Nebreda and Patrick Aloy, Cancer Research, doi: 10.1158/0008-5472.CAN-16-0097, published 22 November 2016.


News Article | November 23, 2016
Site: www.eurekalert.org

A group of researchers at the Centre for Genomic Regulation (CRG) and the Pompeu Fabra University (UPF) in Barcelona, Spain, have developed a new technology that sheds light on the HIV infection and offers a first glance at the expression landscape of the HIV in the human genome. After entering the genome of an infected cell, a fraction of the viruses becomes dormant and hence escapes detection by our immune system. These viruses escape therapy treatment and remain a threat for the patient because, at a later time, they will spontaneously awaken and restart the infection cycle. Many current therapies and available drugs aim to reactivate latent HIV in the hope of clearing the latent virus population. Unfortunately, none of the proposed therapies have proved as yet effective to cure infected patients. Foreign viral DNA is silenced in the human genome by the host chromatin, which is a complex of DNA and proteins wrapping and condensing the DNA to form chromosomes. Chromatin silencing is mediated by several mechanisms and now a team of researchers led by Guillaume Filion, group leader of the Genome Architecture laboratory at the CRG, have developed a technology aimed at discovering the role of the chromatin silencing in the response of latent HIV to the currently available drugs. As reported in Nature Structural and Molecular Biology today, they developed a technology called B-HIVE, which allowed them to map the HIV inserts within the human genome as well as to measure their expression levels. "We barcoded a population of viruses with a genetic identifier. With the barcodes, we were able to link an individual virus to its chromosomal location" explains Filion, the leading author of this study. Genetic barcoding works like the barcodes of food products in supermarkets: after all the items are labeled, each individual item can be identified by its specific code. "Also, we were able to measure their expression levels and showed that the response of HIV to reactivation therapies partly depends on the integration site in the human genome. For the first time, it shows the practical relevance of the chromatin context in the fight against HIV", states the researcher. With the use of this new technology, the researchers were able to show that different HIV reactivation drugs reactivate HIV from different locations within the chromosome. In other words, these drugs are more selective than previously thought. "Having this technique in hand, we can now search for the best drug mix that can reactivate all the latent viruses that up to now were hiding from the antiretroviral drugs in use today and make them susceptible to destruction. Our study suggests to orient future investigations towards the development of drugs with complementary targets" says Heng-Chang Chen, CRG researcher and first author of the study. "This is a big step forward and will definitely boost HIV cure research as well as our understanding of the dormant state of HIV called latency," adds enthusiastically Andreas Meyerhans, an HIV researcher co-authoring this paper and ICREA research professor at the UPF. The new genome-wide maps of HIV expression address a fundamental question that has so far remained unresolved and it provides insight into a basic principles of gene regulation. Hopes are that it will become a favourable and advantageous resource for data analysts interested in clinical applications. While exciting times seem to lay ahead for the researchers, society as a whole can now hope that this exceptional research will be translated into benefit for the community of HIV-infected individuals.


Home > Press > New chip could bring highest level of encryption to any mobile device: First use of quantum technology to create a random number generator that is both tiny and fast Abstract: Random number generators are crucial to the encryption that protects our privacy and security when engaging in digital transactions such as buying products online or withdrawing cash from an ATM. For the first time, engineers have developed a fast random number generator based on a quantum mechanical process that could deliver the world's most secure encryption keys in a package tiny enough to use in a mobile device. In The Optical Society's journal for high impact research, Optica, the researchers report on their fully integrated device for random number generation. The new work represents a key advancement on the path to incorporating quantum-based random number generators -- delivering the highest quality numbers and thus the highest level of security -- into computers, tablets and mobile phones. "We've managed to put quantum-based technology that has been used in high profile science experiments into a package that might allow it to be used commercially," said the paper's first author, Carlos Abellan, a doctoral student at ICFO-The Institute of Photonic Sciences, a member of the Barcelona Institute of Science and Technology, Spain. "This is likely just one example of quantum technologies that will soon be available for use in real commercial products. It is a big step forward as far as integration is concerned." The new device operates at speeds in the range of gigabits per second, fast enough for real-time encryption of communication data, such as a phone or video calls, or for encrypting large amounts of data traveling to and from a server like that used by a social media platform. It could also find use in stock market predictions and complex scientific simulations of random processes, such as biological interactions or nuclear reactions. Shrinking the truly random The random number generators used today are based on computer algorithms or the randomness of physical processes -- essentially complex versions of rolling dice over and over again to get random numbers. Although the numbers generated appear to be random, knowing certain information, such as how many "dice" are being used, can allow hackers to sometimes figure out the numbers, leaving secured data vulnerable to hacking. The new device, however, generates random numbers based on the quantum properties of light, a process that is inherently random and thus impossible to predict no matter how much information is known. Although other researchers have developed quantum random number generators, they have all been either larger or slower than the device reported in the Optica paper. "We have previously shown that the quantum processes taking place exhibit true randomness," said Valerio Pruneri, who led the collaborative research effort. "In this new paper, we made a huge technological advance by using a new design that includes two lasers that interfere with each other in a confined space. This makes the device smaller while keeping the same properties that were used in the past experiments." Creating a practical device The researchers used photonic integrated circuit (PIC) technology to create two quantum number generators that together measure 6 by 2 millimeters. PIC technology offers a way to integrate photonic components -- such as the lasers and detectors used by the new quantum random generator -- onto a chip with a small footprint and low power consumption. Most importantly, PIC-based devices can be integrated with traditional electronics, which could allow the random number generator to be used with the driving, reading and processing electronics necessary for computation or communications. "We proved that quantum technologies are within practical reach by exploiting PICs," said Pruneri. "Quantum random number generation as well as quantum cryptography and other quantum-based technologies will benefit from PIC-based technology because it allows one to build commercial and innovative products. Ours is a first demonstration." This work was a multi-institutional effort that included researchers from ICFO-The Institute of Photonic Sciences, VLC Photonics S.L., Universitat Politècnica de Valencia, ICREA- Institució Catalana de Recerca i Estudis Avancats, all in Spain, as well as Politecnico di Milano in Italy. About The Optical Society Founded in 1916, The Optical Society (OSA) is the leading professional organization for scientists, engineers, students and entrepreneurs who fuel discoveries, shape real-life applications and accelerate achievements in the science of light. Through world-renowned publications, meetings and membership initiatives, OSA provides quality research, inspired interactions and dedicated resources for its extensive global network of optics and photonics experts. For more information, visit osa.org/100. About Optica Optica is an open-access, online-only journal dedicated to the rapid dissemination of high-impact peer-reviewed research across the entire spectrum of optics and photonics. Published monthly by The Optical Society (OSA), Optica provides a forum for pioneering research to be swiftly accessed by the international community, whether that research is theoretical or experimental, fundamental or applied. Optica maintains a distinguished editorial board of more than 40 associate editors from around the world and is overseen by Editor-in-Chief Alex Gaeta, Columbia University, USA. For more information, visit Optica. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article | November 29, 2016
Site: www.eurekalert.org

The Fas protein can either inhibit or promote the controlled cell death (apoptosis), depending on the isoform in which it occurs. Together with international colleagues, researchers from the Helmholtz Zentrum München and the Technical University of Munich have elucidated how this decision is guided. These results provide new insights into the molecular mechanisms of tumor diseases and have now been published in eLife. Please find a video of the PI explaining the story here: https:/ We know the problem: When assembling the parts and pieces of furniture purchased at a store, everyone uses the same blueprint. Nevertheless, the end product can differ greatly in the course of assembling the whole product over several intermediate steps. Something quite similar can happen during the production of proteins from genes. The genome (the blueprint) is first transcribed into a messenger molecule, the mRNA, and then translated into proteins (furniture). However, the mRNA can be altered and trimmed during intermediate steps in a process called alternative splicing, so that ultimately different proteins are produced from the same blueprint. An interesting example of alternative splicing is the mRNA of the Fas gene*. Depending on which intermediate steps take place, the finished protein can either prevent or promote controlled cell death (apoptosis). "The right balance between these opposing results is dependent on the cell type and can also lead to uncontrolled cell growth and cancer when alternative splicing is dysregulated," explains Professor Michael Sattler, Director of the Institute of Structural Biology (STB) at Helmholtz Zentrum München. In collaboration with Professor Juan Valcárcel Juárez of the Centre de Regulació Genòmica (CRG) in Barcelona, he and his team have now gained insight into which intermediate steps are taken and how these lead to different isoforms of the Fas protein. "The focus of our interest was the protein RBM5, which often exhibits mutations in lung tumors," says Dr. André Mourão of the STB. "RBM5 helps to bring the spliceosome to the mRNA by binding to a spliceosomal protein", explains coauthor Dr. Sophie Bonnal of the CRG Barcelona. In this central position, RBM5 decides which isoform of Fas is expressed and thus controls the balance between the two different isoforms.** "By employing nuclear magnetic resonance (NMR) spectroscopy at the Bavarian NMR Center in Garching, we were able to elucidate the spatial structure of RBM5-OCRE in complex with SmN (a protein present in the spliceosome) and to understand exactly how these interaction occurs," states Sattler, who directed the study.*** To confirm their findings, the scientists mutated the corresponding interaction residues of the proteins and observed that the interactions no longer took place in the test tube and that the splicing activities of RBM5 in cell culture was impaired. "The process of alternative splicing affects numerous essential functions and processes in an organism, and dysregulation can trigger cancer. That is why it is very important to precisely understand the mechanisms that regulate these processes," explains Sattler, summarizing the results. According to the authors, only a few protein interactions that influence alternative splicing by binding to spliceosomal proteins have been analyzed in such structural depth. In the future, the researchers want to determine exactly how RBM5 binds to the mRNA and whether there are additional interactions with the spliceosome, which consists of numerous other components. * Fas is also known as CD95 or APO-1. Depending on whether a specific region (exon 6) is contained in the mRNA or not, a membrane-bound pro-apoptotic protein or a soluble isoform arises in the cell interior, which counteracts apoptosis. As a pro-apoptotic protein, Fas prevents errant cells from multiplying uncontrolled, whereas the anti-apoptotic isoform leads to the proliferation of such cells. ** The name is an acronym for RNA Binding Motif 5. RBM5 is a protein, which is demonstrably dysregulated in different cancers (especially in the lungs). *** A so-called OCRE (octamer repeat of aromatic residues) domain of the protein RBM5 binds to the C-terminus of the spliceosomal protein SmN and is thus important for the regulation of the alternative splicing. Background: In addition to his work at Helmholtz Zentrum München, Prof. Dr. Sattler holds the chair of Biomolecular NMR Spectroscopy at Technische Universität München. He heads the Bavarian NMR Center, which is jointly operated by TUM and HMGU (http://www. ). The Institució Catalana de Recerca i Estudis Avançats (ICREA) in Barcelona in Spain (http://www. ) and the Institut de Génétique Moléculaire de Montpellier in France also participated in the study. Publication: Mourão, A. & Bonnal, S. & Soni, K. & Warner, L. et al. (2016): Structural basis for the recognition of spliceosomal SmN/B/B' proteins by the RBM5 OCRE domain in splicing regulation. eLife, doi: 10.7554/eLife.14707 https:/ The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www. The Institute for Structural Biology (STB) investigates the spatial structures of biological macromolecules, their molecular interactions and dynamics using integrated structural biology by combining X-ray crystallography, NMR-spectroscopy and other methods. Researchers at STB also develop NMR spectroscopy methods for these studies. The goal is to unravel the structural and molecular mechanisms underlying biological function and their impairment in disease. The structural information is used for the rational design and development of small molecular inhibitors in combination with chemical biology approaches. http://www. Technical University of Munich (TUM) is one of Europe's leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 40,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, combined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany. http://www. Contact for the media: Department of Communication, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel. +49 89 3187 2238 - Fax: +49 89 3187 3324 - E-mail: presse@helmholtz-muenchen.de Scientific Contact at Helmholtz Zentrum München: Prof. Dr. Michael Sattler, Helmholtz Zentrum München - German Research Center for Environmental Health, Institute for Structural Biology, Ingolstädter Landstraße 1, 85764 Neuherberg, Tel. +49 89 3187 3800, E-mail: sattler@helmholtz-muenchen.de


Far from just reading the information contained in the human genome, and in order to fully understand how it works, researchers aim to know the ins and outs of all the elements in this tiny regulated gear. Many laboratories, consortia and projects are devoted to get a global view of the functional regions of the genome and to know in which cell types genes are active. Intriguingly, only a small fraction of the human genome (around 2%) contains genes encoding for proteins, which are the building blocks of the cell. The remaining 98% is important for regulation, meaning that it is involved in controlling when and where genes are active. This large portion of the genome produces RNA molecules, called non-coding RNAs, which differ in size, structure and function. As the different types of non-coding RNAs can interact with proteins in different ways, big efforts have been put into investigating them. Until now, there were no computational tools available to handle very long RNA sequences and studying them through experimental methods is at present a huge challenge. In a recent article published in Nature Methods, researchers at the Centre for Genomic Regulation in Barcelona (Spain), in collaboration with scientists at EMBL's site in Monterotondo (Italy) and the California Institute of Technology (US), introduced a new computational tool to predict protein interactions with long non-coding RNAs, which they validated using advanced experimental techniques. "Long non-coding RNAs interact with various proteins to mediate important cellular functions. Trying to identify these interactions can be a good starting point in order to understand the role of these molecules in the normal functioning of the cell but also in disease," explains Gian Gaetano Tartaglia, ICREA research professor at the Centre for Genomic Regulation (CRG) and principal investigator of this article. The new computational tool, which is called Global Score, allows scientists to predict where, along the sequence of a non-coding RNA, a protein will establish a physical contact. To do so, this algorithm integrates not only the global propensity of the protein to bind a particular RNA but also the local features of such a binding. "The structure of the RNA is absolutely important when predicting protein interactions. Our main challenge was to be able to work with RNA sequences regardless of their length in order to keep a complete view of their structural properties when looking for protein partners," adds Davide Cirillo, post-doctoral researcher at the CRG and first author of the paper. "The algorithm we have developed integrates this information and allows us not only to predict protein partners but also to prioritize them for experimental validation. This methodological advance will be crucial to better study long non-coding RNAs and their functions", concludes the researcher. This work highlights, again, the relevant contribution of bioinformatics and computational biology to advance knowledge and their key role boosting and accelerating research in the life sciences. More information: Davide Cirillo et al, Quantitative predictions of protein interactions with long noncoding RNAs, Nature Methods (2016). DOI: 10.1038/nmeth.4100


News Article | February 24, 2017
Site: www.eurekalert.org

New algorithm helps scientists prioritize binding partners for experimental validation, which will contribute to our understanding of the role of long non-coding RNAs in normal cell function and in disease Far from just reading the information contained in the human genome, and in order to fully understand how it works, researchers aim to know the ins and outs of all the elements in this tiny regulated gear. Many laboratories, consortia and projects are devoted to get a global view of the functional regions of the genome and to know in which cell types genes are active. Intriguingly, only a small fraction of the human genome (around 2%) contains genes encoding for proteins, which are the building blocks of the cell. The remaining 98% is important for regulation, meaning that it is involved in controlling when and where genes are active. This large portion of the genome produces RNA molecules, called non-coding RNAs, which differ in size, structure and function. As the different types of non-coding RNAs can interact with proteins in different ways, big efforts have been put into investigating them. Until now, there were no computational tools available to handle very long RNA sequences and studying them through experimental methods is at present a huge challenge. In a recent article published in Nature Methods, researchers at the Centre for Genomic Regulation in Barcelona (Spain), in collaboration with scientists at EMBL's site in Monterotondo (Italy) and the California Institute of Technology (US), introduced a new computational tool to predict protein interactions with long non-coding RNAs, which they validated using advanced experimental techniques. "Long non-coding RNAs interact with various proteins to mediate important cellular functions. Trying to identify these interactions can be a good starting point in order to understand the role of these molecules in the normal functioning of the cell but also in disease," explains Gian Gaetano Tartaglia, ICREA research professor at the Centre for Genomic Regulation (CRG) and principal investigator of this article. The new computational tool, which is called Global Score, allows scientists to predict where, along the sequence of a non-coding RNA, a protein will establish a physical contact. To do so, this algorithm integrates not only the global propensity of the protein to bind a particular RNA but also the local features of such a binding. "The structure of the RNA is absolutely important when predicting protein interactions. Our main challenge was to be able to work with RNA sequences regardless of their length in order to keep a complete view of their structural properties when looking for protein partners," adds Davide Cirillo, post-doctoral researcher at the CRG and first author of the paper. "The algorithm we have developed integrates this information and allows us not only to predict protein partners but also to prioritize them for experimental validation. This methodological advance will be crucial to better study long non-coding RNAs and their functions", concludes the researcher. This work highlights, again, the relevant contribution of bioinformatics and computational biology to advance knowledge and their key role boosting and accelerating research in the life sciences.

Loading ICREA collaborators
Loading ICREA collaborators