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News Article | April 20, 2017
Site: www.eurekalert.org

CRG scientists have discovered that the impact of environmental change can be passed on in the genes of tiny nematode worms for at least 14 generations -- the most that has ever been seen in animals Led by Dr Ben Lehner, group leader at the EMBL-CRG Systems Biology Unit and ICREA and AXA Professor, together with Dr Tanya Vavouri from the Josep Carreras Leukaemia Research Institute and the Institute for Health Science Research Germans Trias i Pujol (IGTP), the researchers noticed that the impact of environmental change can be passed on in the genes for many generations while studying C. elegans worms carrying a transgene array - a long string of repeated copies of a gene for a fluorescent protein that had been added into the worm genome using genetic engineering techniques. If the worms were kept at 20 degrees Celsius, the array of transgenes was less active, creating only a small amount of fluorescent protein. But shifting the animals to a warmer climate of 25 degrees significantly increased the activity of the transgenes, making the animals glow brightly under ultraviolet light when viewed down a microscope. When these worms were moved back to the cooler temperature, their transgenes were still highly active, suggesting they were somehow retaining the 'memory' of their exposure to warmth. Intriguingly, this high activity level was passed on to their offspring and onwards for 7 subsequent generations kept solely at 20 degrees, even though the original animals only experienced the higher temperature for a brief time. Keeping worms at 25 degrees for five generations led to the increased transgene activity being maintained for at least 14 generations once the animals were returned to cooler conditions. Although this phenomenon has been seen in a range of animal species - including fruit flies, worms and mammals including humans - it tends to fade after a few generations. These findings, which will be published on Friday 21st April in the journal Science, represent the longest maintenance of transgenerational environmental 'memory' ever observed in animals to date. "We discovered this phenomenon by chance, but it shows that it's certainly possible to transmit information about the environment down the generations," says Lehner. "We don't know exactly why this happens, but it might be a form of biological forward-planning," adds the first author of the study and CRG Alumnus, Adam Klosin. "Worms are very short-lived, so perhaps they are transmitting memories of past conditions to help their descendants predict what their environment might be like in the future," adds Vavouri. Comparing the transgenes that were less active with those that had become activated by the higher temperature, Lehner and his team discovered crucial differences in a type of molecular 'tag' attached to the proteins packaging up the genes, known as histone methylation.* Transgenes in animals that had only ever been kept at 20 degrees had high levels of histone methylation, which is associated with silenced genes, while those that had been moved to 25 degrees had largely lost the methylation tags. Importantly, they still maintained this reduced histone methylation when moved back to the cooler temperature, suggesting that it is playing an important role in locking the memory into the transgenes.** The researchers also found that repetitive parts of the normal worm genome that look similar to transgene arrays also behave in the same way, suggesting that this is a widespread memory mechanism and not just restricted to artificially engineered genes.


News Article | April 20, 2017
Site: www.chromatographytechniques.com

Scientists at the Centre for Genomic Regulation (CRG) in Barcelona and the Josep Carreras Leukaemia Research Institute and The Institute for Health Science Research Germans Trias i Pujol (IGTP) in Badalona, Spain, have discovered that the impact of environmental change can be passed on in the genes of tiny nematode worms for at least 14 generations—the most that has ever been seen in animals. The findings will be published on Friday, April 21, in the journal Science. Led by Ben Lehner, group leader at the EMBL-CRG Systems Biology Unit and ICREA and AXA professor, together with Tanya Vavouri from the Josep Carreras Leukaemia Research Institute and the Institute for Health Science Research Germans Trias i Pujol (IGTP), the researchers noticed that the impact of environmental change can be passed on in the genes for many generations while studying C. elegans worms carrying a transgene array -- a long string of repeated copies of a gene for a fluorescent protein that had been added into the worm genome using genetic engineering techniques. If the worms were kept at 20 degrees Celsius, the array of transgenes was less active, creating only a small amount of fluorescent protein. But shifting the animals to a warmer climate of 25 degrees significantly increased the activity of the transgenes, making the animals glow brightly under ultraviolet light when viewed down a microscope. When these worms were moved back to the cooler temperature, their transgenes were still highly active, suggesting they were somehow retaining the "memory" of their exposure to warmth. Intriguingly, this high activity level was passed on to their offspring and onwards for seven subsequent generations kept solely at 20 degrees, even though the original animals only experienced the higher temperature for a brief time. Keeping worms at 25 degrees for five generations led to the increased transgene activity being maintained for at least 14 generations once the animals were returned to cooler conditions. Although this phenomenon has been seen in a range of animal species - including fruit flies, worms and mammals including humans - it tends to fade after a few generations. These findings represent the longest maintenance of transgenerational environmental "memory" ever observed in animals to date. "We discovered this phenomenon by chance, but it shows that it's certainly possible to transmit information about the environment down the generations," says Lehner. "We don't know exactly why this happens, but it might be a form of biological forward-planning," adds first author of the study and CRG Alumnus, Adam Klosin. "Worms are very short-lived, so perhaps they are transmitting memories of past conditions to help their descendants predict what their environment might be like in the future," adds Vavouri. Comparing the transgenes that were less active with those that had become activated by the higher temperature, Lehner and his team discovered crucial differences in a type of molecular "tag" attached to the proteins packaging up the genes, known as histone methylation. Transgenes in animals that had only ever been kept at 20 degrees had high levels of histone methylation, which is associated with silenced genes, while those that had been moved to 25 degrees had largely lost the methylation tags. Importantly, they still maintained this reduced histone methylation when moved back to the cooler temperature, suggesting that it is playing an important role in locking the memory into the transgenes. The researchers also found that repetitive parts of the normal worm genome that look similar to transgene arrays also behave in the same way, suggesting that this is a widespread memory mechanism and not just restricted to artificially engineered genes.


News Article | April 20, 2017
Site: www.chromatographytechniques.com

Scientists at the Centre for Genomic Regulation (CRG) in Barcelona and the Josep Carreras Leukaemia Research Institute and The Institute for Health Science Research Germans Trias i Pujol (IGTP) in Badalona, Spain, have discovered that the impact of environmental change can be passed on in the genes of tiny nematode worms for at least 14 generations—the most that has ever been seen in animals. The findings will be published on Friday, April 21, in the journal Science. Led by Ben Lehner, group leader at the EMBL-CRG Systems Biology Unit and ICREA and AXA professor, together with Tanya Vavouri from the Josep Carreras Leukaemia Research Institute and the Institute for Health Science Research Germans Trias i Pujol (IGTP), the researchers noticed that the impact of environmental change can be passed on in the genes for many generations while studying C. elegans worms carrying a transgene array -- a long string of repeated copies of a gene for a fluorescent protein that had been added into the worm genome using genetic engineering techniques. If the worms were kept at 20 degrees Celsius, the array of transgenes was less active, creating only a small amount of fluorescent protein. But shifting the animals to a warmer climate of 25 degrees significantly increased the activity of the transgenes, making the animals glow brightly under ultraviolet light when viewed down a microscope. When these worms were moved back to the cooler temperature, their transgenes were still highly active, suggesting they were somehow retaining the "memory" of their exposure to warmth. Intriguingly, this high activity level was passed on to their offspring and onwards for seven subsequent generations kept solely at 20 degrees, even though the original animals only experienced the higher temperature for a brief time. Keeping worms at 25 degrees for five generations led to the increased transgene activity being maintained for at least 14 generations once the animals were returned to cooler conditions. Although this phenomenon has been seen in a range of animal species - including fruit flies, worms and mammals including humans - it tends to fade after a few generations. These findings represent the longest maintenance of transgenerational environmental "memory" ever observed in animals to date. "We discovered this phenomenon by chance, but it shows that it's certainly possible to transmit information about the environment down the generations," says Lehner. "We don't know exactly why this happens, but it might be a form of biological forward-planning," adds first author of the study and CRG Alumnus, Adam Klosin. "Worms are very short-lived, so perhaps they are transmitting memories of past conditions to help their descendants predict what their environment might be like in the future," adds Vavouri. Comparing the transgenes that were less active with those that had become activated by the higher temperature, Lehner and his team discovered crucial differences in a type of molecular "tag" attached to the proteins packaging up the genes, known as histone methylation. Transgenes in animals that had only ever been kept at 20 degrees had high levels of histone methylation, which is associated with silenced genes, while those that had been moved to 25 degrees had largely lost the methylation tags. Importantly, they still maintained this reduced histone methylation when moved back to the cooler temperature, suggesting that it is playing an important role in locking the memory into the transgenes. The researchers also found that repetitive parts of the normal worm genome that look similar to transgene arrays also behave in the same way, suggesting that this is a widespread memory mechanism and not just restricted to artificially engineered genes.


News Article | April 20, 2017
Site: phys.org

Scientists at the Centre for Genomic Regulation (CRG) in Barcelona and the Josep Carreras Leukaemia Research Institute and The Institute for Health Science Research Germans Trias i Pujol (IGTP) in Badalona, Spain, have discovered that the impact of environmental change can be passed on in the genes of tiny nematode worms for at least 14 generations—the most that has ever been seen in animals. The findings will be published on Friday, April 21, in the journal Science. Led by Dr Ben Lehner, group leader at the EMBL-CRG Systems Biology Unit and ICREA and AXA Professor, together with Dr Tanya Vavouri from the Josep Carreras Leukaemia Research Institute and the Institute for Health Science Research Germans Trias i Pujol (IGTP), the researchers noticed that the impact of environmental change can be passed on in the genes for many generations while studying C. elegans worms carrying a transgene array - a long string of repeated copies of a gene for a fluorescent protein that had been added into the worm genome using genetic engineering techniques. If the worms were kept at 20 degrees Celsius, the array of transgenes was less active, creating only a small amount of fluorescent protein. But shifting the animals to a warmer climate of 25 degrees significantly increased the activity of the transgenes, making the animals glow brightly under ultraviolet light when viewed down a microscope. When these worms were moved back to the cooler temperature, their transgenes were still highly active, suggesting they were somehow retaining the 'memory' of their exposure to warmth. Intriguingly, this high activity level was passed on to their offspring and onwards for 7 subsequent generations kept solely at 20 degrees, even though the original animals only experienced the higher temperature for a brief time. Keeping worms at 25 degrees for five generations led to the increased transgene activity being maintained for at least 14 generations once the animals were returned to cooler conditions. Although this phenomenon has been seen in a range of animal species - including fruit flies, worms and mammals including humans - it tends to fade after a few generations. These findings, which will be published on Friday 21st April in the journal Science, represent the longest maintenance of transgenerational environmental 'memory' ever observed in animals to date. "We discovered this phenomenon by chance, but it shows that it's certainly possible to transmit information about the environment down the generations," says Lehner. "We don't know exactly why this happens, but it might be a form of biological forward-planning," adds the first author of the study and CRG Alumnus, Adam Klosin. "Worms are very short-lived, so perhaps they are transmitting memories of past conditions to help their descendants predict what their environment might be like in the future," adds Vavouri. Comparing the transgenes that were less active with those that had become activated by the higher temperature, Lehner and his team discovered crucial differences in a type of molecular 'tag' attached to the proteins packaging up the genes, known as histone methylation. Transgenes in animals that had only ever been kept at 20 degrees had high levels of histone methylation, which is associated with silenced genes, while those that had been moved to 25 degrees had largely lost the methylation tags. Importantly, they still maintained this reduced histone methylation when moved back to the cooler temperature, suggesting that it is playing an important role in locking the memory into the transgenes. The researchers also found that repetitive parts of the normal worm genome that look similar to transgene arrays also behave in the same way, suggesting that this is a widespread memory mechanism and not just restricted to artificially engineered genes. Explore further: Study shows how epigenetic memory is passed across generations More information: Klosin et al. Transgenerational transmission of environmental information in C. elegans. Science. April 21 2017. science.sciencemag.org/cgi/doi/10.1126/science.aah6412


Researchers from ICN2's Phononic and Photonic Nanostructures (P2N) Group at the UAB campus have published a study in which the complex dynamics, including chaos, of optical nonlinearities, are controlled by using optomechanical crystals and changing the parameters of the excitation laser. This discovery might allow the codification of information by introducing chaos into the signal. Optomechanical crystals are designed at nanoscale to allow the confinement of photons and mechanical motion in a common physical volume. Such structures are being studied in complex experimental setups and might have an impact in the future of telecommunications. The interaction of the photons and the mechanical motion is mediated by optical forces leading to a strongly modulated beam of continuous-wave light after interacting with an optomechanical crystal. In optomechanics, optical nonlinearities are usually regarded as detrimental and efforts are made to minimise their effects. ICN2 researchers suggest using them to transport codified information. Initiatives such as PHENOMEN, a European project led by ICN2, lay the foundations of a new information technology combining photonics, radio-frequency (RF) signal processing and phononics. Researchers from the Phononic and Photonic Nanostructures (P2N) Group, led by the ICREA Research Prof. Dr Clivia Sotomayor-Torres at the Institut Català de Nanociència i Nanotecnologia (ICN2), published an article in Nature Communications presenting the complex non-linear dynamics observed in a silicon optomechanical crystal. Dr Daniel Navarro-Urrios is the first author of this study describing how a continuous-wave, low-power laser source is altered after traveling through one of these structures combining optical and mechanical properties of light and matter. The paper reports on the nonlinear dynamics of an optomechanical cavity system. The stable intensity of a laser beam was affected by factors such as thermo-optic effects, free-carrier dispersion and optomechanical coupling. The number of photons stored in the cavity affects and is affected by these factors, creating a chaotic effect that researchers were able to modulate by smoothly changing the parameters of the excitation laser. The authors demonstrate accurate control to activate a heterogeneous variety of stable dynamical solutions. The results of this work set the foundations of a low-cost technology reaching high security levels in optical communications using chaos-based optomechanical cryptographic systems. It is possible to introduce dynamical changes in the light beam traveling through an optical fiber by using an optomechanical crystal. The original light conditions could be reestablished if the parameters of the excitation laser and the optomechanical crystal that introduced those dynamical changes are known. Thus, by linking via optical fibers two integrated chips containing equivalent optomechanical cavities, it is possible to secure information by introducing chaos into the light beam at the emitting point and suppressing it at the reception point. Explore further: An optomechanical crystal to study interactions among colocalized photons and phonons More information: Daniel Navarro-Urrios et al. Nonlinear dynamics and chaos in an optomechanical beam, Nature Communications (2017). DOI: 10.1038/ncomms14965


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 | 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 | 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.


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

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