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The eBook "Bioinformatics for High Throughput Sequencing" is one of the highly accessed ones at Springer

Thu, 13 Jun 2013 22:00:00 GMT

Since its online publication on Oct 25, 2011, there has been a total of 10268 chapter downloads for the book "Bioinformatics for High Throughput Sequencing" (edited by Naiara Rodriguez-Ezpeleta, Michael Hackenberg and Ana M. Aransay) on SpringerLink. This means that this book was one of the top 25% most downloaded eBooks in the relevant Springer eBook Collection in 2012.

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Nanoparticles for controlled drug release

Tue, 11 Jun 2013 22:00:00 GMT

- Researchers from CIC bioGUNE are participating in the study of a novel technique that allows medicines to be transported inside nanoparticles.

- Once these nanoparticles reach their target, drug release is controlled by applying a magnetic field.

- This research, which has recently been published in the Journal of Controlled Release, forms part of the European Nanother project, the aim of which is to design new nanoparticle-based drug-release systems for the diagnosis and treatment of cancer.

(Bilbao, june 2013).- Scientists from CIC bioGUNE and the Laboratoire de Chimie des Polymères Organiques (LCPO) in Bordeaux have jointly undertaken a project to develop "smart" nanoparticles. These polymeric particles act as "nanomissiles" against pre-determined targets and allow the drug to be released in a spatially and temporally controlled manner, only releasing their "load" where it is needed. Release of the medication is controlled by applying a localised magnetic field.

Chemists from the LCPO were responsible for generating the nanoparticles, which are approximately the same size as a virus, whereas researchers from CIC bioGUNE were responsible for assessing their efficacy in a cell culture model. This study was recently published in the Journal of Controlled Release.

The technique developed increases treatment efficacy as it allows the medication to be deposited directly in the affected organ, thereby minimising side effects in other organs. The side effects of any chemotherapy treatment generally arise due to the toxic effects of the drugs administered on healthy tissue (for example hair loss). Indeed, these side effects often mean that the optimal dose cannot be used as it would be far too toxic for the patient.

The system developed by the LCPO/CIC bioGUNE team should allow the drug to be released inside the organ when required. The nanoparticles used to transport the medication are iron oxide-containing polymers. As such, a series of "pores" on the surface of the polymer open up when a magnetic field is applied, thus releasing the drug.

This localised release of the medication should reduce its effect on healthy tissue and may mean that the dose received by cancer cells can be increased. The benefits of this method are therefore decreased side effects and increased treatment efficacy. In the words of the CIC bioGUNE researcher Edurne Berra, "application of a localised magnetic field allows release of the drug and increases its cytotoxic effects on cancer cells".

This work has used doxorubicin, a drug widely used in anti-cancer chemotherapy, as a model. However, its conclusions are likely to be simply the starting point for the development of new, smart release systems for other drugs.

Furthermore, as also noted by Dr. Berra, "the system studied should allow drugs other than doxorubicin to be encapsulated, and it may even prove possible to add molecules that recognise a specific type of cancer cell. It may also find a use for the magnetic resonance-based diagnosis of cancer and even for theragnosis, in other words simultaneous diagnosis and therapy".

Nanother

The study undertaken by CIC bioGUNE and LCPO forms part of Nanother, a major European research project coordinated by Gaiker-IK4, which has a budget of 11 million and involves 18 research institutions from nine European countries. The aim of Nanother is to design new nanotechnology-based drug-release systems for the diagnosis and treatment of cancer.

Reference

Magnetic field triggered drug release from polymersomes for cancer therapeutics.

Hugo Oliveira, Encarnación Pérez-Andrésc, Julie Thevenot, Olivier Sandre, Edurne Berra, Sébastien Lecommandoux.

Journal of Controlled Release. Volume 169, Issue 3, 10 August 2013, Pages 165-170

Wed, 15 May 2013 22:00:00 GMT

- Scientists from CIC bioGUNE, the US National Institutes of Health and the Barcelona Supercomputing Centre have revealed a novel mechanism by which this bacterium manipulates our cells in order to survive inside them

- This discovery may lead to new strategies for fighting legionellosis, a disease that can prove fatal

- Legionella, which lives in freshwater environments, enters our body via the airways when we inhale microscopic drops of contaminated water

(Bilbao, May 2013).- The feared Legionella pneumophila is responsible for legionellosis, an infectious disease that can lead to pneumonia. To infect humans, this pathogen has developed a complex method that allows it to camouflage itself and pass unnoticed inside our cells, thus preventing them from fighting against it.
A study led by the Basque bioscience research centre CIC bioGUNE, together with groups from the US National Institutes of Health (NIH) and the Barcelona Supercomputing Centre (BSC), has described a mechanism that helps this bacterium camouflage itself inside human cells for the first time. This study, which was published today in the prestigious journal PLOS Pathogens, has solved the structure of the Legionella pneumophila protein SidD, which interferes with cell-based processes during infection.

Legionella, which lives in stagnant water, enters our body via the airways when we inhale microscopic drops of contaminated water. Once there, it is phagocytosed (in other words "swallowed") by immune system cells but not destroyed. This occurs because the bacterium manages to manipulate the host cell in order to establish a replicative niche in its interior, where it can hide and multiply without being destroyed.

The strategy employed by the microorganism involves releasing up to 300 proteins inside the cell. These proteins hijack many host's own proteins to modulate cellular processes that prevent the bacterium from being destroyed, thus allowing it to pass unnoticed for long enough to allow it multiply.

One such protein, known as SidD, regulates a chemical modification involved in the intracellular camouflage process. The role of this protein has been described in the study by CIC bioGUNE, the NIH and the BSC. Once Legionella has managed to multiply itself, SidD unblocks cell-based processes that allow the infection to progress.

New targets

"Legionella pneumophila is an organism which, over millions of years of evolution, has learned to manipulate host proteins for its own benefit and thus favour infection", explains the CIC bioGUNE researcher Aitor Hierro. "Understanding how it does so", he adds, "may help us to manipulate our own proteins for our benefit".

The discovery of the mechanism that allows the bacterium to survive and grow in our cells may lead to new strategies. According to Hierro, "this discovery not only suggests new targets that may be used to design inhibitors but also reveals molecular mechanisms that could be readapted and used, for example, in the selective transport of molecules of therapeutic utility".

About legionellosis

Legionellosis was given its name in 1976, when an epidemic outbreak of pneumonia was reported amongst the participants at an American Legion convention in Philadelphia (USA). This disease is caused by the bacterium Legionella pneumophila , which lives in stagnant water and is transmitted in the air when we inhale microdrops of contaminated water in suspension.

The most important sources of infection are water systems or cooling towers in large buildings, such as hotels, hospitals or spas. Contamination in one of these installations may cause an outbreak of legionellosis in people living and working nearby.

Infection by this pathogen can cause two diseases with very different prognoses. The most well known is Legionnaire's disease, a severe respiratory infection that may lead to pneumonia and high mortality if a suitable antibiotic-based treatment is not used.

The other disease is known as Pontiac fever, a much less severe disease that progresses with short episodes of high fever and usually cures itself.

Reference

Structural Basis for Rab1 De-AMPylation by the Legionella pneumophila Effector SidD
Yang Chen, Igor Tascón, M. Ramona Neunuebel, Chiara Pallara, Jacqueline Brady, Lisa N. Kinch, Juan Fernández-Recio, Adriana L. Rojas, Matthias P. Machner, Aitor Hierro.

Ikerbasque y CIC bioGUNE convierten euskadi en un referente internacional en biociencias

Sun, 28 Apr 2013 22:00:00 GMT

o Los 12 investigadores Ikerbasque en CIC bioGUNE han captado más de 3 millones de euros y han publicado más de 50 estudios.

o 5 de los 12 investigadores son de origen vasco. Se trata de investigadores que han desarrollado su carrera fuera de Euskadi y que ahora tienen la posibilidad de seguir investigando en el País Vasco.

o Ikerbasque y CIC bioGUNE han renovado su acuerdo de colaboración para los próximos 5 años.

Zamudio, 29 de abril de 2013.- Ikerbasque y CIC bioGUNE han ratificado hoy el acuerdo de colaboración que firmaron en 2007 con el objetivo de facilitar la atracción de talento científico proveniente de todo el mundo para desarrollar su labor en el centro de investigación con sede en el Parque Tecnológico de Bizkaia.

Actualmente hay 12 investigadores Ikerbaque desarrollando su labor en CIC bioGUNE, lo que supone el 55% de sus investigadores principales, 10 de los cuales se encuentran en el centro de forma indefinida. Se trata de investigadores senior con amplia trayectoria investigadora y capacidad de liderazgo. Recientemente se ha incorporado un joven investigador del nuevo programa Ikerbasque Research Fellow dirigido a jóvenes investigadores/as, con experiencia internacional y prometedora carrera científica, así como un profesor visitante de origen italiano, que estará en el País Vasco durante los próximos 12 meses.

Fernando Cossio, director científico de Ikerbasque y Jose M Mato, director del CIC bioGUNE, han sellado hoy el nuevo convenio con vigencia hasta 2017 acompañados de los investigadores Ikerbasque que desarrollan su trabajo en el centro de investigación. Según Fernando Cossio "Biogune es un magnífico ejemplo de que apostar por la investigación, puede suponer, además de los beneficios a medio-largo plazo que son de todos conocidos, retornos inmediatos que repercuten en el beneficio de toda la comunidad en forma de creación de empleo".

Por su parte, el director general de CIC bioGUNE José M Mato realiza una valoración "muy positiva" de la colaboración con Ikerbasque. "Sin Ikerbasque -afirma Mato- CIC bioGUNE sería un centro menos relevante. La colaboración con Ikerbasque nos ha permitido tener una dimensión más internacional y dotarnos de una visión científica más aplicada".

Hasta la fecha, los investigadores Ikerbasque en CIC bioGUNE han publicado más de 50 investigaciones en revistas científicas de prestigio a nivel internacional y han conseguido fondos por valor de 3.320.000. Esta cifra incluye tanto proyectos competitivos como contratos con empresas.

De los 12 investigadores Ikerbasque, cinco de ellos son de origen vasco, lo que muestra la importancia de este tipo de iniciativas para el "rescate de cerebros", ya que se trata de investigadores que han desarrollado su carrera fuera de Euskadi y actualmente tienen la posibilidad de investigar en el País Vasco.

De entre los trabajos desarrollados por los investigadores Ikerbasque y entre las publicaciones más destacadas a lo largo del último año pueden reseñarse los siguientes:

Moléculas que podrían frenar la metástasis del cáncer de colón: la investigación liderada por Paco Blanco junto a Fernando Cossio, director científico de Ikerbasque, ha llevado a diseñar unas moléculas que han conseguido frenar el desarrollo del cáncer de colon y su metástasis en el hígado en un modelo experimental con ratones. Este avance, que podría abrir una nueva vía para el tratamiento futuro de dichas patologías, se ha conseguido creando unas moléculas que interfieren en la adhesión de las células tumorales con otras células del organismo. De esta forma las moléculas frenan tanto el crecimiento del tumor como la diseminación de las células tumorales y su proliferación en otros órganos.

Investigación sobre el Alzheimer a cargo de Joaquín Castilla, Doctor en Ciencias por la Universidad Autónoma de Madrid y que cuenta con más de 10 años de experiencia en centros de Europa y EEUU. Se incorporó a CIC bioGUNE en 2009 como investigador Ikerbasque. El estudio realizado con ratones por los doctores Castilla y Soto ha arrojado un poco más de luz al mostrar que algunas de las anomalías cerebrales asociadas con la enfermedad de Alzheimer pueden estar relacionadas con procesos infecciosos.

Nueva clasificación de los virus por Nicola Abrescia, Doctor en Ciencias por la Universidad Politécnica de Catalunya. Se incorporo a CIC bioGUNE en 2008 como investigador Ikerbasque. En colaboración con otros científicos de las universidades de Oxford y Helsinki, han dado un vuelco a la clasificación habitual de los virus provocando una "revolución conceptual", En el review científico han intervenido, además del Prof. Nicola Abrescia, distinguidos investigadores dedicados al estudio de virus, como el Prof. Dennis Bamford, de la Universidad de Helsinki, el Dr. Jonathan Grimes y el Prof. David Stuart, ambos de la Universidad de Oxford y este último Director de Ciencias de la Vida del sincrotrón Diamond del Reino Unido. Este equipo científico ha presentado un análisis exhaustivo de los datos que han aportado diferentes investigaciones en las últimas dos décadas, y ha propuesto una novedosa manera de clasificar el universo vírico, radicalmente distinta de las que se ha empleado hasta ahora.

Arkaitz Carracedo fue premiado con una beca de la fundación Susan Komen para la investigación en cáncer de mama en el 22 congreso de la "European Association for Cancer Research", así como con el reconocimiento de ser uno de los trabajos en cáncer más relevantes de los presentados en dicho congreso (Proffered paper award). Estos premios reconocen la labor del grupo de investigación en las bases moleculares del cáncer de mama, según la cual el Dr. Carracedo demostró que los requerimientos metabólicos de este tipo de tumor (su nutrición) desempeñan un papel importante en su desarrollo y agresividad. Este trabajo ha sido publicado en una de las revistas de ámbito clínico de mayor impacto internacional "The Journal of Clinical Investigation".

Soluciones sintéticas para combatir infecciones, a cargo de Juan Anguita, Doctor en Sanidad Animal procedente de la Universidad Massachusetts Amherst. Las infecciones provienen de microbios patógenos (virus, bacterias) que se cuelan en nuestro organismo, se multiplican y se dispersan por él, produciendo enfermedades como la difteria, la hepatitis, la neumonía, etc. El propósito del estudio es llegar a manipular la respuesta que favorezca la eliminación de los patógenos, por ejemplo, incrementando la permeabilidad vascular o generando proteínas que atraigan a células encargadas de eliminar a los patógenos.

Discovery of a gene involved in fatty liver disease

Tue, 23 Apr 2013 22:00:00 GMT

- An international research consortium led by CIC bioGUNE has found that the gene SLC2A1 is associated with non-alcoholic fatty liver disorders, whose complete genetic basis is still unclear.

- Non-alcoholic fatty liver disease is one of the leading causes of chronic liver disease in the world.

(Bilbao, April of 2013).- An international research consortium led by CIC bioGUNE has discovered the involvement of a gene in the development of non-alcoholic fatty liver disease (NAFLD). Although the gene concerned (SLC2A1) had never previously been linked to liver disease, it appears to be involved in the development of this disorder. NAFLD is currently one of the leading causes of chronic liver disease in the world.

It was already known that, as well as environmental aspects (lifestyle, diet, etc.), the likelihood of developing NAFLD was also affected by genetic factors, although the genes concerned are poorly defined. The aim of this study was to identify genetic variants associated with this disease in order to gain a better understanding of the genetics behind its development. The final goal of the study was therefore to try identifying new targets for the diagnosis and treatment of this disease.

This work, which was published recently in the leading scientific journal Hepatology, was undertaken by 20 institutions from Spain, France, Germany, Denmark and the USA, with Basque institutions playing a key role. Thus, as well as CIC bioGUNE, the company OWL Genomics, the Physiology Department at the UPV/EHU School of Medicine and the Galdakao Hospital all took part in this research.

The research

The initial phase of the study involved searching for variations in the DNA sequence of 92 genes, which had shown to be likely candidates by previous studies. DNA from 69 patients diagnosed with NAFLD and 217 health individuals was used. Various genes that exhibited significant differences in their sequence were identified and studied again in a different cohort of 451 NAFLD patients and 304 healthy individuals.

The correlation of NAFLD and high frequency of changes in the sequence for SLC2A1 was found at this stage. Once this relationship had been found, it was studied whether the presence of this gene at an RNA level was the same in the livers of healthy individuals and NAFLD patients. This study showed that RNA from the SLC2A1 gene was present at much lower levels in NAFLD patients.

Finally, an in vitro test with hepatocytes (one of the main cell types in the liver) showed that inhibition of SLC2A1 gene expression resulted in much greater accumulation of lipids than in cells with normal levels of this gene, as well as greater oxidative damage. These are the most representative characteristics of liver status in NAFLD patients.

According to the CIC bioGUNE researcher Ana M. Aransay, who headed the project, "involvement of the SLC2A1 gene in NAFLD still needs to be confirmed in other patient populations from other countries", adding that "as NAFLD is a complex disease, our findings must be interpreted in light of the results of other recent studies".

"Thus", continued Aransay, "an understanding of the development of NAFLD must take into account all the causes of this disease, especially genetic and environmental factors, as well as the interaction between them. An interpretation of the interactions that arise will help us to describe the reality of many complex diseases".

NAFLD

NAFLD is a progressive disease that ranges from fatty liver build-up (steatosis) to non-alcoholic steatohepatitis (NASH), which is inflammation around the fats. Non-alcoholic fatty liver disease is the most common liver disease in Europe and the USA, and its prevalence is currently increasing in many other regions of the world, especially Asia and India.

The prevalence of steatosis and NASH in adults in the Western countries is around 30% and 3%, respectively. NASH is the most serious manifestation of NAFLD as around 20% of NASH patients go on to develop cirrhosis within 10 years, with over a quarter of these patients subsequently developing hepatocellular carcinoma (HCC), or liver cancer, after around 10 years.

Reference

Solute Carrier Family 2 Member1 Is Involved in the Development of Nonalcoholic Fatty Liver Disease

Mercedes Vazquez-Chantada, Aintzane Gonzalez-Lahera, Ibon Martinez-Arranz, Carmelo Garcia-Monzon, Manuela M. Regueiro, Juan L. Garcia-Rodriguez, Karin A. Schlangen, Iñaki Mendibil, Naiara Rodriguez-Ezpeleta, Juan J. Lozano, Karina Banasik, Johanne M. Justesen, Torben Joergensen, Daniel R. Witte, Torsten Lauritzen, Torben Hansen, Oluf Pedersen, Nicolas Veyrie, Karine Clement, Joan Tordjman, Albert Tran, Yannik Le Marchand-Brustel, Xabier Buque, Patricia Aspichueta, Jose J. Echevarria-Uraga, Antonio Martin-Duce, Joan Caballeria, Philippe Gual, Azucena Castro, Jose M. Mato, Maria L. Martinez-Chantar, and Ana M. Aransay.

Hepatology Volume 57, Issue 2, pages 505-514, February 2013

The great human protein 'encyclopaedia'

Sun, 24 Feb 2013 23:00:00 GMT

- The Basque research centre CIC bioGUNE is participating in one of the largest international science projects after the Human Genome Project.

- Bodies from all over the world who have joined together to form the Human Proteome Organisation (HUPO) are participating in this project, which aims to identify all proteins expressed in the human body.

- CIC bioGUNE, which already forms part of the HUPO sub-project aimed at discovering the proteins present in the liver, will also take part in the new initiative aimed at cataloguing all representative proteins coded by the genome.

(Bilbao, 25 February 2013).- The Basque bioscience research centre CIC bioGUNE is an active participant in one of the largest collective studies in world science, namely creation of the great encyclopaedia' of the proteins in the human body. This ambitious initiative, which forms part of the international Human Proteome Organisation (HUPO) project, is aimed at deciphering the proteins expressed by our bodies. The challenge faced by this project is similar in size to that of the Human Genome Project, which in 2001 deciphered the DNA sequence of humans and found that it consisted of 20,300 genes.

HUPO is an international non-profit organisation created in 2003 in which the majority of European countries, the USA, Canada, China, Australia, New Zealand, Brazil, South Korea, Thailand, Taiwan and Japan participate. Its aim is to publish a map of the human proteome, in other words to identify all proteins in the human body. Subsequent application of this knowledge in the healthcare field is expected to lead to the identification of new diagnostic markers and the development of new therapies, especially considering that the vast majority of current drugs act on proteins.

HUPO is a large-scale international project that was initially proposed as having an organ-based approach, in other words a total of 13 research sub-projects aimed at identifying the proteins present in plasma (HPPP, Plasma Project) and human organs such as the brain (HBPP, Brain Project) or liver (HLPP, Liver Project) were launched. Indeed, the head of the proteomics platform at CIC bioGUNE, Félix Elortza, has been participating in the Spanish consortium involved in the latter project from the outset.

As the work has progressed, it has been found that concentrating the search for human proteins on organs and plasma has several drawbacks as the proteins expressed in the various organs are very similar. As a result, the project has been redefined somewhat, without abandoning the projects cited above, and, as a result, the HUPO platform has created a new major project to search for the proteins coded by genes, known as the Chromosome-Centric Human Proteome Project (C-HPP).

This major international project, which was launched recently, is intended to identify at least one protein coded by each of the 20,300 genes in the human genome. Genes code proteins that play a specific role. As such, the C-HPP project has been divided into 24 working groups, one for each human chromosome. Chromosomes are segments into which DNA is divided and can contain from a few genes (chromosome Y) to as many as 2000 (chromosome 1).

In order to confront the huge scale of this challenge, each of these working groups comprises various research centres from the same country. The chromosomes were shared out between those countries with the greatest experience in the field of proteomics, the discipline that studies the proteins expressed by a cell, tissue or organism.

A special edition of the Journal of Proteome Research in which the results obtained to date by the C-HPP initiative are described has been published recently.

- Chromosome 16

The Spanish working group was assigned the study of the representative proteins for each gene coded by chromosome 16. The aim of the initial phase of this study is to detect those proteins coded by this chromosome that had not been detected previously. To this end, a total of 16 research centres and institutes came together to form ProteoRed-ISCIII, the Spanish proteomics research network. These centres include CIC bioGUNE, with funding from the BBVA Foundation.

Although the majority of diseases cannot be linked to genes from a single chromosome, it is thought that chromosome 16 codes for genes related to cancer, obesity, neurodegenerative diseases, metabolic diseases, etc. It is estimated that at aproximalety one third of the proteins coded by chromosome 16 have never been detected.

The project, which is still in its preliminary phases, is testing new mass spectrometry methods (an ultra-sensitive technique that allows proteins to be detected and quantified) that should allow a very high level of protein detection and quantification to be achieved. This will allow several proteins to be monitored in a single experiment, thus increasing, for example, our ability to discover new molecular mechanisms and providing the possibility to achieve a better diagnosis.

According to Félix Elortza, "this international project has provided ProteoRed-ISCIII with the opportunity to play an active role in the first human proteome map". "Although the map we generate will only be version 1.0, it will nevertheless allow us to place Spanish proteomics laboratories at the forefront of this scientific achievement and will also help to speed up the development of the highly sensitive analytical methods required by a project of this type", states Dr. Elortza.

"Needless to say, this would result in the development of more complex biomedical projects that will help to clarify currently unresolved problems and result in improved diagnosis, prognosis and discoveries in the field of biomedicine", concludes the CIC bioGUNE researcher.

- Proteins

Proteins are a type of biological macromolecule which, together with lipids, nucleic acids (DNA and RNA) and polysaccharides, are the main building blocks of all living things. Proteins are involved in almost all cell processes and are constructed from a sequence of small molecules (amino acids); the order of this sequence is determined by the genes. In a series of biological processes, cells manufacture proteins, which become authentic cell-based tools with multiple roles (structural, mechanical, immune response, etc.). The sequence of proteins is determined by each of the genes revealed by the Human Genome Project.

References for the study

Spanish human proteome project: dissection of chromosome 16

Segura V, Medina-Aunon JA, Guruceaga E, Gharbi SI, González-Tejedo C, Sánchez Del Pino MM, Canals F, Fuentes M, Casal JI, Martínez-Bartolomé S, Elortza F, Mato JM, Arizmendi JM, Abian J, Oliveira E, Gil C, Vivanco F, Blanco F, Albar JP, Corrales FJ.

Journal of Proteome Research 2013 Jan 4;12(1):112-22.

CIC bioGUNE researchers to take part in the Basque Network of Food Safety Experts

Wed, 20 Feb 2013 23:00:00 GMT

- This network will support the Food Safety Scientific Committee who advise the Basque Government

(Bilbao, 21 february 2013).- CIC bioGUNE researchers -Mikel Valle, Nicola Abrescia, Juan Anguita and Jokin Castilla- will join an expert network providing advice to the Basque Foundation for Agro-food Safety (Elika) to share their knowledge with this Basque public body when needed.

The expert network which the CIC bioGUNE researchers will become part of, will be comprised of experienced specialists, professionals and scientists, operating in fields which are directly or indirectly related to the Agro-food sector. Their role will be to support the Food Safety Scientific Committee (FSSC) by providing their know-how, creating expert groups, assessing specific risks or covering a specific field of knowledge, as and when required. Moreover, the researchers will be in charge of the preparation of progress reports and scientific statements.

The CIC bioGUNE researchers joining this network are Mikel Valle and Nicola Abrescia, of the Structural Biology Unit, and Juan Anguita and Jokin Castilla of the Proteomics Unit.

The FSSC is a consultation body which is part of Elika and advises the Basque Government on scientific matters before decision-making aimed at reducing or minimising risks related to the agro-food chain. With this in mind, this body identifies, evaluates and classifies the health hazards derived from the population's exposure to the physical, chemical or biological agents found in food.

Novel designed molecules could stop colon cancer metastasis

Wed, 13 Feb 2013 23:00:00 GMT

- A Basque research consortium has carried out a study in mice showing that novel synthetic molecules stop the growth of colon cancer and its propagation to the liver.

- This work opens the possibility for the future development of modified molecules with improved pharmacological properties for clinical trials.

(Bilbao, 14th of February, 2013).- A Basque research consortium has managed to stop the development of colon cancer and its liver metastasis in an experimental model using mice. This breakthrough, which could open new avenues for the future treatment of these pathologies, has been achieved by creating molecules that interfere with the tumour cells adhering to other cells in the body. In this way, these molecules stop both the tumour growth and the spreading of tumour cells to other organs and their subsequent proliferation.

The study, published today in the renowned American magazine Journal of Medicinal Chemistry', is based on a previous work by a research group of the University of the Basque Country, which described a series of molecules that reduced metastasis in melanoma (a severe type of skin cancer) in mice. That work opened the possibility of generating new molecules to act on other types of cancer by following a similar strategy. This is what the current research has achieved, applied to colon cancer and liver metastasis.

The Basque research consortium is made up by the Basque research centre in bioscience, CIC bioGUNE, the University of the Basque Country (UPV/EHU), the Institute of Genetics and Molecular and Cellular Biology (IGBMC) from Strasbourg, France and the spin-off company Ikerchem. They have also received the collaboration of researchers from the Institute of Physical Chemistry "Rocasolano" (IQFR), from CSIC, and from the Novartis Institute for BioMedical Research.

"In this project we initially designed inhibitors of the cellular adhesion involved in the metastasis of murine melanoma, and then we carried out the chemical synthesis of these molecules, checking their potency and their biological activity. The surprise was that our calculations predicted that by introducing relatively small changes we could generate new molecules able to inhibit cell adhesion involved in a different type of cancer. This prediction was confirmed by the experimental results, thus suggesting that these techniques of chemical design and synthesis may be applied to other related therapeutic targets", says Dr. Fernando Cossío, professor at the UPV/EHU, co-founder of Ikerchem S.L. and president of the Ikerbasque Executive Committee.

"As well as being relevant for the control of cancer and metastasis, this work shows that in the Basque Country there are teams of researchers in academic institutions and in companies with the necessary experience and collaboration capacity to address multidisciplinary projects of biomedical relevance, by combining synthetic and computational chemistry with the structural analysis of the mechanism of action and the biological validation of the generated molecules", states Dr. Francisco Blanco, Ikerbasque Research Professor at CIC bioGUNE.

Impact of cancer and metastasis

Cancer is the second highest cause of human mortality and its incidence increases with age. Thanks to the progress in early detection and the control of detected tumours, the survival rate has been steadily increased and, in this sense, it is expected that further progress in these two aspects of the disease will be achieved.

Nowadays, 90% of deaths from cancer are caused by the reappearance of the original tumour in a different part of the body, a process known as metastasis. This process takes place when a cancer cell from the original tumour migrates to another organ in the patient's body, generating a new tumour.

Colon cancer, is not among the highest mortality rate cancers, but it often develops metastasis in the liver, which it is. In fact this is the organ where most frequently the metastasis from tumours in other parts of the body appear. This happens because the liver works as a blood and lymph filter and, therefore, cancer cells in these fluids may be trapped in it.

The lethal danger of cancer cells moving around the body is what pushes the researchers to find therapies to stop metastasis.

References for the study:

Design, Synthesis, and Functional Evaluation of Leukocyte Function Associated Antigen-1 Antagonists in Early and Late Stages of Cancer Development

Eider San Sebastián, Tahl Zimmerman, Aizpea Zubia, Yosu Vara, Elyette Martin, Finton Sirockin , Annick Dejaegere , Roland H. Stote , Xabier Lopez, David Pantoja-Uceda, María Valcárcel, Lorea Mendoza, Fernando Vidal-Vanaclocha, Fernando P. Cossío, and Francisco J. Blanco.

Eight years of biosciences

Wed, 16 Jan 2013 23:00:00 GMT

- Research centre CIC bioGUNE is celebrating its eighth anniversary with a conference by Catalan researcher Modesto Orozco

The Basque Center for Cooperative Research in Biosciences, CIC bioGUNE, is eight years old, and to celebrate it has organised a plenary lecture on Friday 18 January by Catalan researcher Modesto Orozco. The conference, which will take place in the building 800 at the Bizkaia Technology Park at 1 pm, is entitled "Simulating DNA from nucleobases to the chromatin" and will deal with the recent breakthroughs in multiscale simulation of DNA, and how these advances can decode a hidden part of the genetic code. Modesto Orozco is one of the greatest experts in the use of computers to describe the structure of proteins and nucleic acids.
The Catalan researcher leads the Molecular Modelling and Bioinformatics group at IRB Barcelona, is a Biochemistry and Molecular Biology professor at the University of Barcelona, director of the Life Sciences Department at the Barcelona Supercomputing Center (BSC), director of the joint computational biology programme at IRB Barcelona/BSC, and director of the Structural Bioinformatics node at the Spanish Institute of Bioinformatics (INB).
Orozco has published more than 350 papers in renowned scientific journals, which have received more than 11,000 citations. As well as many awards, Orozco was given an ERC Advanced Grant in 2012, one of the most prestigious grants given by the European Scientific Council.

Analía Núñez-O'Mara defends her PhD thesis on January 16th, 2013

Tue, 08 Jan 2013 23:00:00 GMT

Analía Núñez-O'Mara will defend her PhD thesis, entitled " HIF Prolil Hidroxilasa 3 (PHD3), un doble centinela en la regulación de HIF: Implicación de la modificación por SUMO ", on January 16th, at 11.30h. The event will take place in "Salón de Grados de la Facultad de Ciencia y Tecnología", at the University of Basque Country.

A new path for the future generation of glucose-measuring biosensors

Wed, 02 Jan 2013 23:00:00 GMT

- CIC bioGUNE researchers have proven the close connection between proteins that were thought to be completely independent and isolated

- This discovery could lead to new glucose measurement methods in blood, which is essential to control diabetes, a chronic disease which affects more than 300 million people worldwide

- Current techniques measure glucose concentration in blood, but other more reliable sensors are being researched, based on other fluids such as urine, for example

(Bilbao, 2013-01-03).- CIC bioGUNE researchers have opened a new path for the future development of biosensors that enable glucose measurement in the blood and also in other fluids that are thought to be more effective, such as urine. For this, a complex scientific process has been developed in which a prevailing paradigm in the scientific community concerning the binding and communication mechanisms between proteins was questioned.

Subcellular communication mechanisms are based on the interaction between proteins, or between proteins and metabolites and other ligands. These phenomena help to explain most of the protein functions in living organisms, but in order to do so it is essential that each protein knows exactly to which ligand it must be bound.

Until now, the scientific community widely believed that there was a double binding mechanism between proteins, which was differentiated and isolated like two independent process: some proteins were bound just with one mechanism called "induced fit" (the protein takes the form of the ligand during the association process), while other proteins were bound exclusively with the so called "conformational selection" mechanism (like a lock that needs a key with defined characteristics, the binding process between a protein and a ligand will take place insofar as its shapes enable said fit).

This project, however, led by Dr Óscar Millet, from the Structural Biology Unit at CIC bioGUNE and published in the November issue of the Journal of the American Chemical Society, refutes this paradigm and states that slight modifications introduced with genetic engineering in the hinge regions between two proteins are enough to alter the actual binding mechanism.

To develop this study, two bacterial periplasmic binding proteins were taken as models. These proteins are bound with a spectacular conformational change (closing two domains round a hinge region) which is similar to the process that carnivorous plants use to trap insects between their fleshy lobes.

"The main result of our work is proving that both mechanisms are intimately connected and that we can go from one to another just by introducing small modifications in the protein," explains Óscar Millet.

"Not only have we understood this mechanism, but we have seen that the difference between this induced fit and the conformational selection is very subtle; they are actually not two independent processes - everything is connected. Nature is always subtle, and small variations to the chemical composition of the hinge lead us from one mechanism to the other," added the CIC bioGUNE researcher.

"This mechanism is completely governed by the hinge region to the point that by exchanging the hinges using genetic engineering, the change of mechanism also happens: the GGBP with the RBP hinge acts with induced fit and vice versa, the RBP with the GGBP hinge binds to the substratum with lock-and-key mechanism," Millet declares.

"By understanding the mechanism by which periplasmic proteins trap glucose to insert it into the cells, these molecules could be used as biosensors", explains Millet. Thanks to these biosensors, glucose concentration could be measured in fluids other than blood, for example urine. This would make the process easier and would provide more reliable data than traditional glucose concentration measurement methods in the blood of diabetes patients.

The techniques that are used today can only give an approximate measurement of blood glucose concentration, as there are other substances that hide it. Any advance, therefore, in the search for new diagnosis methods will improve the control of the disease.

Diabetes

It is very important for diabetes patients to measure their glucose concentration, as diabetes is a serious chronic disorder that affects more than 300 million people worldwide, and 5 million in Spain. This metabolic disease is caused by low production of a hormone - insulin - in the pancreas or when the body does not use this hormone properly. Insulin is involved in the transport of glucose to the interior of the cells, which turn it into useful energy.

In diabetics, the low generation of insulin or inadequate usage in the body leads to an excessive blood glucose concentration and causes many symptoms such as tiredness, weight loss, neuropathies, sight problems and in extreme cases, death.

References for the study

Carbohydrate Affinity for the Glucose-Galactose Binding Protein Is Regulated by Allosteric Domain Motions

Gabriel Ortega, David Castaño, Tammo Diercks and Oscar Millet. Structural Biology Unit, CIC bioGUNE, Bizkaia Technology Park, Building 800, 48160 Derio, Spain

J. Am. Chem. Soc., 2012, 134 (48), pp 19869-19876

Famelab, el certamen internacional de monólogos científicos, llega a España

Mon, 10 Dec 2012 23:00:00 GMT

FameLab nació en 2005 gracias a una idea original del Festival de Cheltenham, cuyo principal objetivo era fomentar la divulgación de la ciencia identificando, formando y dando a conocer nuevos talentos entre los que trabajan en ciencia a través de un formato innovador, el monólogo científico.

Desde 2007, gracias a la asociación con el British Council, FameLab se ha vuelto global, celebrándose a día de hoy competiciones en más de 20 países de Europa, Asia, África y Estados Unidos. A nivel mundial son ya más de 3.800 personas las que han participado en alguna de sus ediciones.

FameLab se propone apoyar y animar a las personas que trabajan en ciencia a utilizar sus habilidades comunicativas para hacer llegar el contenido de su trabajo a la sociedad en su conjunto, no sólo a sus colegas y compañeros.

El concurso consta de las siguientes fases:

1ª fase (Preselección) - Selección de los participantes que pasarán a la segunda fase a partir de las presentaciones orales grabadas en vídeo. Envío de los videos hasta el 31 de enero.

2ª fase (Masterclass) - Los seleccionados en la primera fase recibirán una formación por parte de expertos en técnicas de comunicación que les capacitará para la 3ª fase, además de aumentar sus habilidades comunicativas.

3ª fase (Final nacional e internacional) - Presentación oral realizada delante de un jurado y del público y proclamación por parte del jurado el vencedor de la fase nacional que participará en la final internacional en el Cheltenham Science Festival en junio de 2013.

LKB1: Friend or foe?

Sun, 09 Dec 2012 23:00:00 GMT

- Researchers from CIC bioGUNE have found that LKB1 protein, which is commonly used to inhibit the proliferation of breast, lung and cervical cancers, stimulates the growth of liver cancers in mice.

- This discovery may lead to therapeutic applications in the fight against this type of cancer, which is one of the most dangerous and difficult to treat.

(Bilbao, 10th December 2012).- Researchers from the Metabolomics Unit at CIC bioGUNE, led by Dr. María Luz Martínez Chantar, have discovered that LKB1 protein, which is well known in oncology to inhibit the growth of breast, lung and cervical tumours, has the opposite effect in hepatocellular carcinomas (HCCs), in some cases inducing their malignant transformation in mice.

The study, which was published in the prestigious US journal Gastroenterology lately, has revealed a previously unknown molecular mechanism involved in the development of HCC by showing that the malignancy of this disease may be related to the increased activity of a protein known as liver kinase B1 (LKB1).

As noted by Dr. Martínez Chantar, "in the field of oncology, LKB1 is generally thought to act by inhibiting tumour growth. And this is precisely one of the key discoveries of this research, as in the case of hepatocellular carcinoma, activation of LKB1 appears to stimulate the oncogenic pathways that result in the proliferation of anomalous cells and induce malignant transformation".

HCC, which is responsible for around 90% of all liver cancers, is the fifth most common cancer in the world and the third cause of cancer-related death after lung and gastric cancer. This tumour has a very poor prognosis, even in developed countries, and its incidence is similar to its mortality rate, thus meaning that most patients die within a few months despite recent diagnostic and therapeutic breakthroughs. Furthermore, as it is a very heterogeneous tumour the scientific community has renewed its efforts to establish very precise and personalised therapeutic targets.

Conventional oncological treatment options for HCC are limited as this strongly chemoresistant tumour often develops in cirrhotic livers. Approximately 40% of patients are diagnosed with HCC in an advanced stage and as such have a life expectancy of one year in 29% of cases and two years in 16% of cases.

This cancer is unique in oncology as, despite its high incidence and poor prognosis, until recently there was no effective therapy available. A possible explanation for this fact is the high heterogeneity of the molecular mechanisms involved in the development of this tumour.

"Now we have discovered that LKB1 may play a key role in the development and progress of HCC, our next step will involve a comprehensive study of its potential therapeutic applications", concludes Martínez Chantar.

Reference of the study:

Hepatoma cells from mice deficient in glycine N-methyltransferase have increased RAS signaling and activation of liver kinase B1

Martínez-López N, García-Rodríguez JL, Varela-Rey M, Gutiérrez V, Fernández-Ramos D, Beraza N, Aransay AM, Schlangen K, Lozano JJ, Aspichueta P, Luka Z, Wagner C, Evert M, Calvisi DF, Lu SC, Mato JM, Martínez-Chantar ML.

Gastroenterology. 2012 Sep;143(3):787-98.e1-13. doi: 10.1053/j.gastro.2012.05.050. Epub 2012 Jun 8.

A joint study between the CNIO and CIC bioGUNE identifies metabolomic biomarkers that could prove useful in preventive molecular medicine

Tue, 04 Dec 2012 23:00:00 GMT

- These findings were obtained in a study of 1500 metabolites in blood, thus making it the most in-depth analysis to date in this research field.

- The work, which is published today in the on-line version of the journal Aging Cell, is an important breakthrough in the field of preventive molecular medicine and the identification of new biomarkers for early detection of disease risk.

Madrid, 5 December 2012. A better understanding of the origin of diseases in order to improve their early detection and therefore improve their cure rates is one of the greatest challenges facing biomedicine. Such progress would also benefit what CNIO scientists refer to as preventive molecular medicine, which consists of identifying those individuals who are at highest molecular risk of suffering certain diseases in order to prevent them. Ageing of the body, and therefore the cells and tissues of which it consists, is the most significant risk factor for the majority of diseases in the developed world, including cancer.

A team of scientists from the Spanish National Cancer Research Centre (Centro Nacional de Investigaciones Oncológicas, CNIO), led by its head María Blasco, together with Jose M. Mato, head of the Center for Cooperative Research in Biosciences (CIC bioGUNE), has shown that the metabolic profile of a body indicates its degree of cellular ageing and general health status in mice. These findings may prove to be of great use in the field of preventive molecular medicine as they could indicate health status in a fast and minimally invasive manner, thus helping to prevent diseases or to diagnose them in their early stages.

Metabolism is one of the processes that best defines an organism's general status. As such, in order to study the possible relationship between metabolism and ageing, the authors of this study used a new methodology involving liquid chromatography and mass spectrometry techniques to study up to 1500 metabolites (metabolic intermediaries or products) in very small samples (only 5-10 µL) of blood serum from 130 mice.

"This new technique has allowed us to demonstrate that the metabolic profile of mice depends on their biological age; specifically, we have found that the levels of 48 metabolites vary very significantly with age", states CNIO researcher Bruno Bernardes de Jesús, one of the authors of this study.

When the researchers performed the same analyses in mice expressing a higher level of telomerase, which, according to a study published recently by Blasco's group in the journal EMBO Molecular Medicine, age more slowly, they found that the metabolic signature was very similar to that found in younger mice. The same analyses in telomerase-deficient mice, which age more quickly, gave a metabolic signature which closely resembled that found in older mice.

Recent studies in humans have shown a possible relationship between metabolism and life expectancy. "Our large-scale analyses, which include the largest number of metabolites analysed to date, confirm the theory that the metabolome reliably reflects the biological clock of cells", declares Jose M. Mato, a researcher at CIC bioGUNE.

NEW BIOMARKERS FOR ASSESSING HEALTH STATUS

Ageing is mainly characterised by a metabolic decline that results in a loss of liver, kidney, coronary and heart function as well as a higher risk of cancer. Indeed, some of the 48 metabolites identified in this study have previously been linked to age-related diseases such as Alzheimer's or cardiovascular disease.

The results of this research may prove useful for predicting the overall health status of humans from a small sample of blood. They may also prove useful for preventing the age-related diseases that make up the majority of fatal diseases in the developed world.

In light of their findings, these researchers intend to search for diagnostic biomarkers associated with other health problems with a high socio-economic impact, such as diabetes, obesity or cardiovascular disease.

Reference article:
A metabolic signature predicts biological age in mice. Antonia Tomás-Loba, Bruno Bernardes de Jesus, Jose M. Mato, Maria A. Blasco. Aging Cell (2012). doi: 10.1111/acel.12025

Jevgenia Tamjar defends his PhD thesis on December 3th, 2012

Thu, 29 Nov 2012 23:00:00 GMT

Jevgenia Tamjar will defend his PhD thesis, on December 3th, at 11:30 o'clock. The event will take place in "Sala anexa al Paraninfo", at the University of Basque Country (Leioa).

David Fernández Ramos defends his PhD thesis on December 5th, 2012

Wed, 28 Nov 2012 23:00:00 GMT

David Fernández Ramos will defend his PhD thesis, entitled "New Oncogenic Drivers in Hepatocellular Carcinoma: Role of the RNA Binding Protein Hu Antigen R", on December 5th, at 12 o'clock. The event will take place in "Salón de grados de la facultad de medicina", at the University of Basque Country.

Algunos de los retos pasados y futuros de la Virología Estructural

Tue, 20 Nov 2012 23:00:00 GMT

Los virus se extienden por toda la biosfera. Algunos de ellos son patógenos para los seres humanos y los animales; otros son nuestros aliados al infectar y controlar la proliferación de bacterias indeseadas. Indudablemente estas maquinarias miniaturizadas e ingeniosas comparten nuestra existencia probablemente desde antes de que ocurriera la división en los tres dominios de la vida: Bacteria, Eukarya y Archaea. Sin embargo, no hay fósiles para los virus, por lo que establecer conexiones entre virus basándose en homología de secuencia normalmente no permite ir más allá de la comparación entre miembros de una misma familia viral. Poder determinar relaciones entre virus aparentemente distintos significaría poder conceptualizar y diseñar posible estrategias comunes de defensa antiviral.

La Virología estructural, a través del análisis tridimensional (3D) de las proteínas víricas y de los virus enteros -bien sea por cristalografía de rayos X o bien por microscopía electrónica-, ha facilitado el análisis sistemático y comparativo del plegamiento de las proteínas de la cápsida. Estas proteínas, capaces de constituir la caja fuerte del genoma viral pueden ser consideradas como las huellas del ancestro común.

Link al articulo

¿Podemos poner a dieta el cáncer?

Mon, 19 Nov 2012 23:00:00 GMT

Arkaitz Carracedo de la Unidad de Proteómica nos explica en una entrevista en Radio Euskadi, cómo se produce y desarrolla el cáncer, y cómo las investigaciones sobre el metabolismo de las células tumorales lo señala como un método de detección de tumores y el origen de posibles tratamientos.

Audio: http://t.co/r9kzfrFb

Jornada de divulgación

Wed, 14 Nov 2012 23:00:00 GMT

En la jornada se abordará la relación existente entre la alimentación y la felicidad, así como la influencia en nuestro estado emocional y en el estilo de vida que desarrollemos.

Toda la información relativa al evento, aqui

CIC NETWORK reúne a representantes políticos para debatir sobre política científica

Wed, 10 Oct 2012 22:00:00 GMT

Racionalizar el sistema vasco de ciencia, tecnología e innovación y alcanzar la media europea en inversión en I+D+i para el año 2015 fueron los dos objetivos compartidos por los representantes de EAJ-PNV, PSE-EE, PP y EH Bildu en el II Fórum CIC Network sobre Política Científica celebrado el 11 de octubre en nuestras instalaciones

Forum on Scientific Policy this October 11th at 11:00am

Thu, 04 Oct 2012 22:00:00 GMT

Con motivo de la próxima convocatoria de elecciones al Parlamento Vasco, el próximo día 21 de octubre, la revista CIC Network -impulsada por la red de Centros de Investigación Cooperativa (CIC) de Euskadi- ha convocado un Fórum sobre política científica, en la que participarán representantes de las principales fuerzas políticas que concurrirán a dicha convocatoria electoral (EAJ-PNV, PSE-EE, PP y EH-Bildu).

El Fórum CIC Network sobre Política Científica se celebrará el día 11 de octubre, a las 11.00 horas., en las instalaciones de CIC bioGUNE, en el Parque Tecnológico de Bizkaia (Derio), Edificio 800. El acceso será libre y gratuito, hasta completar aforo. El Fórum será moderado por el director general de CIC bioGUNE y CIC biomaGUNE, José M Mato, y director de la revista CIC Network, y consistirá en una breve introducción por parte de cada uno de los representantes políticos sobre su estrategia en materia de política científica e I+D. Posteriormente, se celebrará un debate con los asistentes a dicha jornada.

La duración de este Forum CIC Network sobre Política Científica será de una hora y media aproximadamente.

II International Workshop held at CIC bioGUNE

Sun, 30 Sep 2012 22:00:00 GMT

- International experts will discuss recent technological advances and the applications of these techniques in a conference entitled "Metabolomics & Proteomics. Technology and Applications" to be held in Derio (1-3 October).

- These disciplines are applied in fields ranging from new drug development to biomarker identification and environmental pollutant detection.

(Bilbao, 1 October 2012).- CIC bioGUNE is shortly to host a conference that will discuss the latest progress in two essential technologies in modern biology, namely metabolomics and proteomics. Over three days (1-3 October), international experts in these fields, which have probably had the greatest impact over the past few years on our understanding of biological systems, will gather under the auspices of the Second International Metabolomics and Proteomics Workshop entitled "Technology and Applications"

The meeting will be held at the site of the Center for Cooperative Research in Biosciences CIC bioGUNE at the Bizkaia Technology Park in Derio and will cover the latest progress in the field of single-cell, high-throughout metabolomics, large-scale protein characterisation or quantification, and the potential applications of these technologies in fields such as pesticide detection in food, novel drug development and biomarker identification.

Metabolomics and proteomics are currently considered to be two key disciplines in the field of systems biology as they allow aspects such as the functioning of organs and living beings to be studied in great detail.

Metabolomics

Metabolomics is the study of metabolites, in other words molecules with a very low molecular mass that are produced during metabolism, including amino acids, sugars or lipids. Metabolism is the term used to describe all the physical and chemical processes in an organism that produce the energy and biomolecules required for life.

"Identifying metabolites helps us to understand how the metabolism in an organ or living being works. This technique will therefore help us to study complex biological processes, the efficacy and toxicity of new drugs or the mechanism by which a disease progresses", states Dr. Juan Falcón, an Ikerbasque researcher at CIC bioGUNE and one of the conference coordinators.

In this edition, Dr. Christoph Borchers, from the University of Vancouver (Canada), will describe the latest progress of our understanding of how our intestinal flora works using metabolomics. Similarly, Dr. Karsten Hiller, from the Biomedical Research Centre in Luxembourg, will present the findings that have allowed his group to characterise a new defence mechanisms in cells that helps them to dispose of the toxic agents produced during metabolism.

The talk by Dr. Rick Dunn, from the University of Manchester, who will present the most recent methodological advances in the study of biological samples of great interest for the diagnosis of metabolic diseases, is also one of the highlights.

Proteomics

Proteomics is the study of the set of proteins expressed by a cell, tissue or organism. As proteins are produced by genes, the sequencing of an organism's genome should allow us to analyse the pattern of numerous proteins simultaneously. "Changes in expression between healthy and diseased samples will allow us to gain a better understanding of the molecular mechanisms of the disease", notes Dr. Félix Elortza, a researcher at CIC bioGUNE and conference coordinator. "Experiments of this type allow us to lay the foundations for detecting new drugs as the majority of drugs used today target a protein", he adds.

The most important speakers in this field include Prof. Richard Simpson, from the Trobe Institute for Molecular Science, (Victoria, Australia), who will discuss the characterisation of exosomes secreted by colon cancer cells, and Dr. Corrales, from CIMA in Pamplona, who will present the latest findings of his proteomics-based study of liver diseases. The presentation by Dr. Juan Pablo Albar, who will describe the Spanish contribution to the detection of all proteins encoded by chromosome 16, an initiative that forms part of the Human Proteome Project (HUPO), in which CIC bioGUNE's proteomics platform is also involved, is also worthy of mention.

First 1st Board Meeting of the UPStream Consortium organized by CIC bioGUNE in Bilbao

Sun, 30 Sep 2012 22:00:00 GMT

CIC bioGUNE leads the UPStream project, an excellence training program for young scientists investigating the biochemical process of ubiquitylation and other related modifications. The 1st Supervisory Board Meeting will take place in the AlhóndigaBilbao during the 1st and the 2nd of October. The event will bring together more than 20 participants, leading scientists in Biomedical research from seven different European countries.

The Centre for Cooperative Research in Biosciences CIC bioGUNE was selected to lead the UPStream project, with an allocated funding of 3.3 million euros, focusing on specific training of 12 young scientists in the biochemical process of ubiquitylation and other related processes. The project will last 48 months and officially started last November. The student hired by CIC bioGUNE joined the team in January this year.

UPStream, coordinated by CIC bioGUNE researcher Rosa Barrio , focuses on a critical and complex field in modern biology: understanding the regulation of post-transcriptional modifications and the ubiquitin-dependent protein degradation system (UPS, ubiquitin-proteasome system), and its potential application in drug development.

First symposium of leading Spanish scientists who use Drosophila in their biomedical studies

Sun, 30 Sep 2012 22:00:00 GMT

More than 40 scientists from 11 centres, including CIC bioGUNE, bear out the strength of the science performed with the fruit fly in Spain.

CIC bioGUNE scientists David Gubb and Rosa Barrio participated in the 1st Spanish Conference Series on the Molecular, Cellular, and Developmental Biology of Drosophila. The conference was held in Aiguablava, Girona, from the 25th to the 28th of September and was organized by Jordi Casanova and Cayetano González, CSIC and ICREA research professors respectively, scientists from the Institute for Research in Biomedicine (IRB Barcelona). The conference brought together for the first time more than 40 leading Spanish scientists of international standing that use Drosophila melanogaster in their biomedical research.

Drosophila melanogaster, popularly known as the fruit fly or vinegar fly, has been used to determine the bases of biology. This tiny insect lies behind the work of six Nobel laureates in medicine and is now one of the key models in biomedical labs throughout the world. For historical reasons, the Drosophila fly has made a fundamental contribution to the progress of science in Spain and international recognition of the same. "In spite of this strength, never before has an event been organised to bring together all the experts in this field in Spain. We are covering a historical gap and show the international dimension of our research", explains Dr. González, head of the Cell Division Laboratory at IRB Barcelona, which is developing the "FlyCan" project, an initiative that has received funding of 2 million euros from the European Research Council (ERC) to further our understanding of cancer using the Drosophila fly.

The symposium seeks to identify synergies and boost opportunities for collaboration between research groups belonging to 11 centres, of which five are in Barcelona (IRB Barcelona, Center for Genomic Regulation, Institut de Biologia Molecular de Barcelona, Institut de Biologia Evolutiva and Universitat de Barcelona), three in Madrid (Centro de Biología Molecular Severo Ochoa (CBM), Instituto Cajal and Universidad Autónoma de Madrid), plus Instituto de Neurociencias de Alicante, Centro Andaluz de Biología del Desarrollo, in Seville, and CIC bioGUNE in the Basque Country.

The congress involves expert groups in cutting-edge fields such as epigenetics and genomics, proliferation and tumour formation and metastasis, hormonal regulation and immunity. Until only a few years ago, almost all research in Spain was undertaken in the CBM, thanks to Antonio García Bellido, who, in 1969, started pioneering studies with this insect. "There are now groups all around Spain and IRB Barcelona has amassed several Drosophila labs that cover a wide variety of biomedical fields" explains Dr. Casanova. Casanova heads the Morphogenesis in Drosophila group, which studies the development of this insect, with special attention on cell migration and its relation with metastatic processes in cancer.

The researchers aim to hold the Spanish Conference Series on the Molecular, Cellular, and Developmental Biology of Drosophila periodically. The conferences are part of an ambitious project at IRB Barcelona headed by Jordi Casanova, Cayetano González and Marco Milán, called the FlyCenter. This interdisciplinary initiative aims to optimize technical resources and scientific platforms for groups working with Drosophila, to organise international meetings, and to perform projects in collaboration with centres worldwide to model human diseases in Drosophila.

CIC bioGUNE y CIC biomaGUNE, dos centros, un objetivo

Mon, 17 Sep 2012 22:00:00 GMT

- Ambos centros de investigación en biociencias y biomateriales cuentan con más de 200 investigadores y han acometido inversiones por valor de 75 M desde 2005.

- Han obtenido 158 M procedentes de programas competitivos de ayuda a la investigación, fundaciones y contratos de investigación con empresas.

- Presentarán sus credenciales en BioSpain 2012 como estandartes de la investigación científica en el ámbito bio'.

(Bilbao, 17 de septiembre de 2012).- Los centros de investigación cooperativa en biociencias y biomateriales, CIC bioGUNE y CIC biomaGUNE respectivamente, presentarán sus credenciales como referentes de la investigación científica en el ámbito bio' en Euskadi, en el marco de BioSpain 2012 - ocuparán los stands D15-D17 del recinto ferial-, que tendrá lugar entre los días 19 y 21 de septiembre en el Bilbao Exhibition Center (BEC).

Ambos centros de investigación, dirigidos por el Prof. José María Mato, tienen como objetivo la promoción de la investigación científica y la innovación tecnológica de primer nivel en el País Vasco, en el marco de la Estrategia Biobasque, de cara a contribuir a la creación y consolidación de un nuevo sector económico basado en las biociencias.

Un indicador del nuevo contexto que ha irrumpido en el País Vasco en los últimos años (2005-2012) es que el número de empresas vinculadas a las biociencias o a la nanotecnología se ha duplicado, pasando de 49 a 80; un sector que en la actualidad genera cerca de 4.000 empleos.

CIC bioGUNE, con sede en el Parque Tecnológico de Bizkaia, y CIC biomaGUNE, con sede en el Parque Tecnológico de San Sebastián, se han erigido en baluartes de la investigación científica en el ámbito de las biociencias y los biomateriales en Euskadi, y aglutinan en su seno a más de 200 investigadores y técnicos de investigación.

Entre los años 2005 y 2012, CIC bioGUNE y CIC biomaGUNE han acometido inversiones por valor de 75 M, vinculadas a infraestructuras y equipamientos en imagen molecular, genómica, proteómica, metabolómica, RMN (Resonancia Magnética Nuclear), microscopía electrónica, etc.

En este sentido, han obtenido alrededor de 158 M procedentes de programas competitivos de ayuda a la investigación de programas regionales, nacionales y europeos, fundaciones y contratos de investigación con empresas.

Las inversiones tienen un fin último, como es dotar a los centros de equipamientos técnicos y materiales punteros para hacer ciencia de primer nivel, en áreas de interés estratégico como, entre otras, nanomateriales biofuncionales, biosuperficies, imagen molecular, metabolismo y enfermedad, cáncer y envejecimiento, enfermedades infecciosas, etc.

Ambos centros destinan anualmente un total de 20 M en investigación, y dedican otros 7,5 M para contratar investigadores académicos, investigadores post doctorales, técnicos e ingenieros, y también para ofrecer oportunidades de formación a doctores y estudiantes de master.

CIC bioGUNE y CIC biomaGUNE cuentan con 30 investigadores principales o group leaders, que han sido reclutados a través de convocatorias internacionales, de los que 17 son investigadores asociados a programas como Ikerbasque, Bizkaia:xede y Ramón y Cajal.

Iñigo Urkullu visita las instalaciones de CIC bioGUNE

Wed, 12 Sep 2012 22:00:00 GMT

El Presidente del Partido Nacionalista Vasco (EAJ-PNV) y candidato a Lehendakari en las próximas elecciones autonómicas del 21 de octubre, Iñigo Urkullu, visitó las instalaciones de CIC bioGUNE el pasado día 11 de septiembre.

El candidato jeltzale', que estuvo acompañado por la parlamentaria Estíbaliz Hernáez, mantuvo una reunión con el director general de CIC bioGUNE y CIC biomaGUNE, José M Mato, y el director financiero de ambos centros, Alfonso Egaña, reunión que sirvió para dar a conocer a Iñigo Urkullu la dimensión y objetivos científicos de los dos centros.

Posteriormente, realizaron una visita por los laboratorios de la Unidad de Biología Estructural de CIC bioGUNE, en la que estuvieron presentes también, entre otros, los investigadores Oscar Millet, Mikel Valle y Joaquín Castilla.

Pubmed ratings place the CIC bioGUNE Animal Units work in the top 10

Tue, 11 Sep 2012 22:00:00 GMT

The publication "Clinical biochemistry parameters in C57BL/6J mice after blood collection from the submandibular vein and retroorbital plexus" (Fernandez et al., 2010), was the third most downloaded article (1903 hits) of the Journal of the American Association of Laboratory Animal Science (JAALAS) from Pubmed Central in 2011 (see table 5 in page 247 in reader survey). JAALAS is recognized as one of the top international journals in the field of laboratory animal medicine.

Full access to article

The therapeutic potential of cellular fat oxidation in bone-marrow transplants and breast cancer

Mon, 03 Sep 2012 22:00:00 GMT

- Dr. Arkaitz Carracedo of Biogune takes part in two studies which provide evidence for a crucial role of the PML protein in the regulation of cellular fat oxidation, with important implications in physio-pathological processes

- The first study, published in The Journal of Clinical Investigation, suggests that PML inhibition could have therapeutic potential in a subset of breast cancers

- The second study, featured in Nature Medicine, reveals the requirement for fat oxidation, which is also regulated by PML, in the generation of blood cells from stem cells

(Bilbao, 4th September 2012) - Altered fat accumulation and metabolism in developed societies is of increasing health and aesthetic concern. There is, however, more to this process than simply the impact of lipid accumulation on the body. Lipids are one of the most concentrated energy sources known, thus making them an invaluable nutrient for our cells under challenging conditions. Despite this, little is known about the impact of fat-oxidation processes on cell fitness.

Two independent studies in which Arkaitz Carracedo, Ikerbasque Research Professor at Biogune, has taken part in collaboration with the world-leading research team headed by Pier Paolo Pandolfi at Harvard Medical School, have unravelled how known and novel components of the lipid oxidation regulation machinery impact cell and body fitness. In these studies, a well-described tumour suppressor, namely promyelocytic leukaemia protein (PML), which ensures that cells behave correctly and keeps cancer cells in check, is shown to be a new regulator of the fat-oxidation process (also known as fatty acid oxidation, or FAO). The metabolic activity of PML, in turn, reveals novel and paradoxical functions for this protein.

The first study, published in the September issue of the Journal of Clinical Investigation, defines the mechanism by which PML modulates FAO (by regulating peroxisome proliferator-activated receptors, PPARs) and shows that alterations in this pathway result in excessive fat accumulation and the development of obesity in mouse models. "Surprisingly, by regulating metabolism, PML exerts a paradoxical activity in breast cancer, where instead of keeping breast cancer cells under control, it provides a selective advantage under conditions of metabolic challenge", says Dr. Carracedo.

This observation is correlated with the increase in PML levels in a subset of breast cancer specimens and its association with poor prognosis. This study therefore provides puzzling evidence of an unexpected activity of PML in breast cancer, where, instead of keeping cancer cells under control, it provides them with the energy they need to survive. "These findings have changed our vision of PML and have led us to study whether drugs used to inhibit PML in leukaemia can also be used to treat breast cancer", adds Arkaitz Carracedo.

The second study, carried out jointly with Dr. Keisuke Ito (now at the Albert Einstein College of Medicine), has defined for the first time the contribution of lipid metabolism to the maintenance and function of haematopoietic stem cells, the source of the haematopoietic lineage. This work, published in the September issue of Nature Medicine, describes how haematopoietic stem cells require high levels of FAO in order to maintain their undifferentiated state. Indeed, the pharmacological or genetic inhibition of this metabolic pathway (which is regulated by PML and PPAR delta), means that such stem cells are no longer able to sustain blood cell supply, whereas its activation enhances the ability of these cells to replenish the haematopoietic compartment in bone marrow transplants.

"The idea that this pathway may be relevant to the function of blood stem cells is really exciting since it opens the door to the possibility that we may be able to reduce the amount of material needed for bone marrow transplants by using drugs that regulate this route. We hope that future research will determine whether such drugs can provide a benefit to the patient", says Arkaitz Carracedo.

What can we learn from these studies? First of all, fat oxidation is of tremendous relevance to both normal and cancer cells. These two studies cover the impact of the process on different aspects of biomedical research, especially obesity, breast cancer and haematopoietic stem cell maintenance. "But, more importantly, the pathway described therein is highly amenable to pharmacological manipulation. PML, PPARs and FAO can be modulated using compounds that are either already available or have already passed toxicity and tolerability evaluations in clinical trials", says Dr. Carracedo.

"As a result, understanding the relevance of this novel pathway in obesity, haematopoietic stem cell maintenance and breast cancer could potentially lead, with further investigation, to the establishment of novel pharmacological approaches to the treatment of related pathologies in the future", concludes Arkaitz Carracedo.

Bibliographic reference:

Nature Medicine:
A PML-PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance
Keisuke Ito, Arkaitz Carracedo, Dror Weiss, Fumio Arai, Ugo Ala, David E Avigan, Zachary T Schafer, Ronald M Evans, Toshio Suda, Chih-Hao Lee & Pier Paolo Pandolfi

Journal of Clinical Investigation:
A metabolic prosurvival role for PML in breast cancer
Arkaitz Carracedo, Dror Weiss, Amy K. Leliaert, Manoj Bhasin, Vincent C.J. de Boer, Gaelle Laurent, Andrew C. Adams, Maria Sundvall, Su Jung Song, Keisuke Ito, Lydia S. Finley, Ainara Egia, Towia Libermann, Zachary Gerhart-Hines, Pere Puigserver, Marcia C. Haigis, Elefteria Maratos-Flier, Andrea L. Richardson, Zachary T. Schafer and Pier P. Pandolfi

Synthetic solutions to combat infections

Mon, 09 Jul 2012 22:00:00 GMT

Biogune researcher, Juan Anguita, in collaboration with scientists of the University of Massachusetts, has proven the efficiency of synthetic antimicrobials.

These synthetic compounds have a double effect, on the one hand, they combat infections directly, and on the other they activate the immune system.

Even in pre-clinical studies, they have become good candidates for the treatment of infectious diseases, such as conjunctivitis, meningitis and pneumonia.

Infections come from microbes (virus, bacteria) that enter our system, multiply and spread through it. These microbes, which produce diseases such as diphtheria, hepatitis, pneumonia, etc., are known as pathogens. The goal of medicine is to act against the consequences of these pathogens in people. Similarly, the goal of scientific research is to better understand their functioning to develop solutions to control these pathogens.

An international team of scientists, including Ikerbasque Biogune researcher, Dr. Juan Anguita, in close collaboration with Dr. Gregory Tew, of the University of Massachusetts Amherst (UMASS), published a paper in the Journal of the American Chemical Society -one of the journals of highest impact in Chemistry -, in which they have proven the effectiveness of synthetic antimicrobial compounds that, in addition to

eliminating infections, stimulate the immune system, which helps fight infection.

The project sought to study the behaviour of certain synthetic compounds, based on natural peptides, which have been developed by a US company (Polymedix), that have a high antimicrobial activity against different micro-organisms.

The research team started to study these compounds based on the function of certain antimicrobial natural peptides that have the aforementioned dual activity, in other words, fighting against external agents while activating the immune system. The idea, therefore, was to imitate the immune response of the human body in a synthetic compound, with a positive result.

To provoke this activation of the immune system, the researchers have focused on macrophages, which are cells that act very quickly at the beginning of an infection, giving prompt response to the disease. Macrophages react immediately when, for example, we injure ourselves, to promote healing. They are also responsible for tattoos becoming permanent marks on our skin, since they are responsible for recognising ink

as a strange object entering the organism.

Good candidates to fight diseases

The result of the study concludes that the dual action of these synthetic compounds can result in a better effectiveness in fighting against infection. Furthermore, the low toxicity of these compounds, has turned them into great candidates for the treatment of a broad range of infectious diseases, with the added advantage that, given the nature of these compounds, the appearance of treatment-resistant strains, as in the case of antibiotics, is improbable or non-existent.

These compounds are still undergoing pre-clinical studies, but they have become good candidates for the treatment of a great range of infectious diseases, including conjunctivitis, meningitis and pneumonia, given the low toxicity and their effectiveness to fight against infections.

"The greatest advantage of these compounds is, on the one hand, the duality of their function, directly achieving the elimination of pathogens (because they are antimicrobial), and indirectly, through the manipulation of the function of macrophages", says Dr. Anguita.

The purpose of this study is to manipulate a response that favours the elimination of these pathogens, for example, increasing vascular permeability or generating proteins attracting cells responsible for eliminating pathogens, such as macrophages and neutrophils. In short, in Dr. Anguita's opinion, "the idea is to generate a two-punch response, with direct elimination and through cell mechanisms, for example, phagocytosis, generating toxic compounds for bacteria like oxygen radicals, etc."

"In this study we measured the stimulating activities of cytokines and chemoattractant products produced by macrophages by a panel of compounds (SMAMPs - Synthetic Mimics of Antimicrobial Peptides), and one of them was identified as a stimulant on its own and in combination with LPS. We observed that this immunomodulatory capacity is due to the modulation of the production of IL-10 regulatory cytokine", concludes Dr. Anguita.

Viruses find new ancestors

Tue, 26 Jun 2012 22:00:00 GMT

- Biogune researchers and scientists from the Universities of Oxford and Helsinki propose a radically different structure-based classification of viruses.

- Virus classification has been traditionally based on their genetic material and on the host cells they infect.

- This new organization shows significant similarities between viruses that infect very different organisms such as bacteria and humans.

We are surrounded by viruses. And we are not referring to those that "infect" our computers. We are referring to those microscopic infectious agents that multiply in the cells of other organisms, like plants, bacteria, archaea and animals, including human beings.

As an example, when we swim in the sea we are surrounded by millions of these microscopic agents (e.g. there are ~10⁷ viruses per millilitre only on the sea surface). We only know an infinitesimal number of these infectious agents, and, of this small group, the scientific community has only managed to decode the 3-D structure of a limited number of them.

Researchers at the Structural Biology Unit at the Biogune, in collaboration with scientists of the Universities of Oxford and Helsinki, have challenged the usual classification of these agents provoking a true "conceptual revolution", in the words of Nicola G.A. Abrescia, Ikerbasque Professor at Biogune and one of the researchers participating in the review published in the prestigious Annual Review of Biochemistry, one of the scientific journals with the highest impact factors.

Viruses are basically composed of a genome (DNA or RNA) and a capsid, in other words, a protein structure that envelopes and protects this genetic material. Some have a lipid vesicle enveloping the capsid and, in other cases, the vesicle is surrounded by the capsid. Until now, viruses were classified considering their genetic material or the type of "hosts" that they infected.

This classification is broadly accepted by the international scientific community. However, this classification has certain inconveniences: it is complex, it does not classify all the known viruses and it does not establish any sort of relation between viruses infecting different types of organisms.

In this study they have shown that some viruses have capsids with very similar proteins, even though they infect completely different organisms. Traditional classifications consider that these viruses have no relationship between themselves, because they do not infect the same type of organisms.

Review

This scientific review has been authored by Prof. Nicola Abrescia, and worldwide recognized scientists involved in the study of viruses such as Prof. Dennis Bamford, of the University of Helsinki, Dr. Jonathan Grimes and Prof. David Stuart, of the University of Oxford and the latter also Director of Life Sciences of the Diamond Synchrotron in the UK.

This scientific team has presented a comprehensive analysis of the data accumulated over the last two decades and have proposed a new way of classifying the viral universe, which is radically different from what has been used until now.

"The publication of this review in this scientific journal represents a recognition of our proposal, since it shows the impact and relevance of this new way of classifying viruses", says Abrescia on the impact of the article by being published in such an internationally renowned journal.

New proposal

In this new proposal they have not considered which organism the viruses infects but its identity, considering as identity (or virus self') the 3-D structure of the protein forming the capsid. Logically, this scientific breakthrough can only focus on the small range of viruses "decoded" by the scientific community, i.e. those viruses in which the structure of the protein of the capsid has been identified.>

Of the 82 families of viruses that had been proposed in a previous classification (2008), the researchers have managed to group almost half in four large families, which implies an important simplification of the classification of the virus world by establishing (until now) the four main families mentioned above.

"The virus taxonomy as it is today is sometimes hard to grasp, we have tried to rationalise it. Apparently unrelated viruses, are now related with our new approach. By using the capsid structure we have generated four viral lineages, which simplifies the vision of the virus world", say Abrescia.

Additionally, the system proposed by the researchers in the Annual Review of Biochemistry allows to relate viruses that were considered completely different since they infect different organisms.

For example, they have noted that, in terms of the structure of the capsid, adenoviruses that infect humans causing respiratory diseases are similar to PRD1, which infects bacteria. With this approach it has been possible to detect a partial similarity between the capsid of herpes virus and phage HK97.

These findings, highlights Abrescia, "could open the door to the use of similar strategies against viruses that had not been considered related so far but that share similar capsid structures."

Ancestral viruses

Another implication deriving from the new classification is the fact that the viruses affecting different domains of life (bacteria, animals, etc.) are so similar, thus indicating a common ancestor origin, which would be prior to the separation in the three domains of life millions of years ago.

In other words, it is believed that all living creatures descend from one shared universal ancestor (LUCA). This organism evolved in different ways, thus originating the current domains (archaea, bacteria y eukaryote).

The fact that some viruses infecting very different domains, such as humans and bacteria, share very similar capsid protein structures, could imply that they come from shared ancestral viral lineages prior to the separation of the living creatures in the aforementioned branches.

Nicola G.A. Abrescia is Ikerbasque Professor hosted by the CIC bioGUNE at the Structural Biology Unit. Abrescia's research is focused on studying very large macromolecular complex such as viruses, with particular emphasis to those viruses with a lipidic vesicle such as Hepatitis C virus and bacteriophage PRD1, using electron microscopy and X-ray crystallography techniques.

Personal info.

References for the study

Structure Unifies the Viral Universe.

Nicola G.A. Abrescia, Dennis H. Bamford, Jonathan M. Grimes, and David I. Stuart. Annual Review of Biochemistry, July 2012.

http://www.annualreviews.org/doi/abs/10.1146/annurev-biochem-060910-095130

CIC bioGUNE to hold exosome expert meeting

Mon, 25 Jun 2012 22:00:00 GMT

- The meeting will gather the Spanish work group that studies exosomes, formed after the last conference in Gothenburg organised by the International Society for Extracellular Vesicles. The group aims to promote the study of exosomes in the field of clinical diagnosis.

- Exosomes are small vesicles secreted by cells towards the outside to transfer material and send signals to other cells. They regulate the immune response and are involved in the development and progression of cancer.

- Exosomes have opened an innovative research area in the field of non-invasive diagnosis of diseases, because they can be isolated in saliva, blood and urine samples

(Bilbao, 26 June 2012).- CIC bioGUNE is holding a meeting of the group of Spanish researchers specialising in exosomes (GEIVEX) on Thursday, 28 June. This group was formed after the international conference on extracellular vesicles, which took place recently in Gothenburg (Sweden). More than 600 research groups from all over the world attended this conference. At the conference, Spanish researchers decided to form a work group to contribute to the dissemination and integration of these small vesicles into the field of clinical diagnosis in Spain.

The following people are attending the meeting, organised by Ikerbasque researcher at CIC bioGUNE, Dr Juan M. Falcón Pérez: Dr Hernando del Portillo, from the CIBEK - Biomedical Research Centre Esther Koplowitz in Barcelona; Dr Francesc Borràs, from the LIRAD-BST in Badalona; Dr Antonio Marcilla, from the University of Valencia; Dr María Yañez-Mo, from the IIS Princesa Health Research Institute in Madrid; and Dr María Mittelbrunn Herrero from the CNIC in Madrid.

The aforementioned researchers will discuss, amongst other topics, ways to promote the study of extracellular vesicles, in collaboration with hospitals, as an innovative biological source of identifying non-invasive markers of diseases. They will also plan specialised courses and national conferences focusing on this field of research.

What are exosomes?

Exosomes are small vesicles secreted by cells towards the outside to transfer material and send signals to other cells. These vesicles take part in different normal biological and pathological processes such as, the regulation of the immune system against different allergens, or in the development and progression of cancer.

Extracellular vesicles are detected in different body fluids such as saliva, blood and urine, and their protein and nucleic acid content provides information on the origin and the physiological condition of the cell releasing the vesicles. This gives them great potential in the area of non-invasive diagnosis of diseases. Furthermore, because many pathogens are able to secrete these vesicles, different infectious diseases may be detected in the early stages, not only in humans but also in animals that are important for agriculture.

Exosomes have great potential for the future in the field of nanotechnology and regenerative medicine, as tools that can be customised for the controlled release of bioactive substances (e.g. genes, proteins or drugs) to a certain type of cell, tissue or organ.

When fat meets inflammation: NK cells are to blame

Sun, 03 Jun 2012 22:00:00 GMT

- Researchers from the Center for Cooperative Research in Biosciences, CIC bioGUNE (Bizkaia), led by Dr. Naiara Beraza, have found that NK cells play a key role in promoting liver inflammation at early stages of non-alcoholic steatohepatitis (NASH), a critical step previous to cirrhosis and hepatocarcinoma development.

- This study, recently published in Hepatology, underlines the therapeutic potential of NK cell inactivation and inhibition of TRAIL expression to counteract the progression of NASH

(Bilbao, 5th of June, 2012).- Obesity, considered nowadays as epidemic in the Western countries, is strongly linked to liver steatosis. Fat accumulation in the liver (steatosis), can be considered as a benign condition in patients and might be chronified for life. However, steatosis may lead to esteatohepatitis; the chronic inflammation of the liver. This condition has strong detrimental consequences for the liver and is considered as the point-of-no-return' of non-alcoholic steatohepatitis (NASH disease) progression.

Inflammation promotes fibrogenesis, cirrhosis and finally hepatocellular carcinoma (HCC). HCC represents the third leading cause of death in cancer patients. All these urge the need to identify the molecular mechanisms leading to chronic inflammation in the context of NASH progression and the identification of new molecular targets for early diagnosis and treatment.

Researchers led by Dr. Naiara Beraza have developed a work in the Metabolomics Unit Lab of Biogune, directed by Dr. Martinez Chantar, that highlights the role of NK cells as the main promoters of inflammation at early stages of NASH development. Moreover, they proved that TRAIL strongly mediates the detrimental role of NK cells.

This work has been published in the journal Hepatology', and uncovers a new mechanism by which TRAIL-producing NK cells promote liver inflammation in steatotic livers from Glycin-N-Methyl-Transferase (GNMT) deficient mice. S-adenosylmethyonine (SAMe) is the main methyl donor of the body and GNMT is the enzyme that catabolizes it. Interestingly, patients with cirrhosis show downregulation of GNMT, which expression is completely absent in HCC.

"TRAIL is a well-know therapeutic tool to treat several types of tumors in patients as this cytokine, produced by NK cells, kills only transformed or virally infected cells. However, our work highlights the detrimental effect of NK cell activation and TRAIL production in steatotic livers as this promotes hepatocyte cell death leading to chronic inflammation; the pathogenic condition that precedes cirrhosis and HCC development. Moreover, our work shows that hepatocytes lacking GNMT, which accumulate lipids, actively express ligands of NK cells leading to the recognition of those hepatocytes as damaged or transformed and thus promoting their death through TRAIL-mediated mechanisms", explains Dr. Beraza.

Complex process

The pathogenesis of NASH is a complex process involving many cellular events; lipid accumulation, apoptosis, inflammation, fibrogenesis and tumorigenesis among others. An important part of the pathogenesis of NASH involves bacterial overgrowth and permeabilisation of the gut, which exposes the liver to a great amount of endotoxin.

"Macrophages are classically described as the main cell compartment to counteract endotoxin-mediated liver injury", explains Dr. Beraza. "Interestingly, we have found that GNMT deficiency sensitizes the liver to endotoxin-mediated liver damage and that this injury is mediated by TRAIL-expressing NK cells whereas macrophages seem to play a less important role in this process. In this direction, we have proven that inactivation of NK cells and/or impairment of TRAIL production protects the liver against bacterial insult at early stages of fatty liver disease".

Overall, the work of the researchers lead by Dr. Beraza defines the essential role of TRAIL-producing NK cells in mediating liver injury when GNMT is absent and points to this cell compartment as potential mediator of chronic inflammation in the onset of NASH progression. Also, data suggest the therapeutic potential of early detection of NK cell activation and further blockade of TRAIL production and activity of these immune cells to counteract liver inflammation in the scenario of liver steatosis. "We have provide further evidences of the relevance of the innate immune system in the biology of the liver and the important role of NK cells in the pathogenesis of NASH", concludes Dr. Beraza.

References for the study:

- Inhibition of NK cells protects the liver against acute injury in the absence of GNMT.

Gomez-Santos L, Luka Z, Wagner C, Fernandez-Alvarez S, Lu SC, Mato JM, Martinez-Chantar ML, Beraza N. Hepatology. 2012 Mar 5. [Epub ahead of print]

Ugo Mayor

Wed, 23 May 2012 22:00:00 GMT

Ugo Mayor, from Laboratory 4 at Functional Genomics Unit, have collaborated in the book "Ubiquitin Family Modifiers and the Proteasome" with the chapter titled "Deciphering tissue-specific ubiquitylation by mass spectrometry".

Abstract

Protein ubiquitylation is a highly conserved, central mechanism to regulate cellular events in all eukaryotes, such as proteasomal degradation, protein trafficking, DNA repair, synaptic plasticity, and immune response. The consequence of protein ubiquitylation is modulated by the structure of ubiquitin (Ub) moiety attached on the substrates, including ubiquitin monomer and diverse polyubiquitin chains with different linkages (N-terminus, K6, K11, K27, K29, K33, K48, and K63). The development of ubiquitin-enrichment strategies coupled with sensitive mass spectrometry enables direct analysis of ubiquitylated proteins in cells, providing an invaluable tool for ubiquitin research. In this chapter, we describe recent technology updates for analyzing tissue-specific ubiquitin conjugates in transgenic models, as well as targeted proteomics methods for quantifying different polyubiquitin chain linkages in any type of -samples, including human tissues.

NCBI link

Chapter available here

New non-invasive test for fatty liver disease diagnosis developed

Mon, 21 May 2012 22:00:00 GMT

- Researchers at Biogune, in collaboration with OWL Genomics, CIBERehd and eleven hospitals and research centres from Spain, France and United States, have developed the first metabolome-based serum test for the non-invasive diagnostic of non-alcoholic fatty liver disease or NAFLD

- Diagnosis for NASH, an advanced NAFLD disease, is presently done trough a liver biopsy, an invasive, subjective procedure with potential complications

(Bilbao, May 23th, 2012).- Researchers at Biogune in collaboration with OWL Genomics, CIBERehd and eleven hospitals and research centres from Spain, France and the United States, have developed the first metabolome-based serum test for the non-invasive diagnostic of nonalcoholic fatty liver disease or NAFLD.

NAFLD is a progressive disease that ranges from the simple accumulation of fat (steatosis), to nonalcoholic steatohepatitis or NASH (inflammation around the fat). NAFLD is the most common liver disease in Europe and the United States and its prevalence is increasing in many other parts of the world, such as Asia and India. The prevalence of steatosis and NASH in Western adults is around 30% and 3%, respectively. NASH is the most serious form of NAFLD, about 20% of NASH patients develop cirrhosis in 10 years, and more than one-fourth of these patients group develop hepatocellular carcinoma or HCC (cancer of the liver) in 10 years.

NASH diagnosis is presently done histologically and requires a liver biopsy. Liver biopsy is an invasive, subjective procedure with potential complications (risk of death about 0.01%) and prone to sample error. Imaging techniques, such as MRI and ultrasound imaging (ecography), perform as well as liver biopsy for fat measurement, but cannot distinguish simple steatosis from NASH. Because these limitations of liver biopsy and imaging techniques, NAFLD patients will benefit from this new noninvasive metabolome-based NASH predictor.

The study analyzed 467 biopsied individuals with normal histology (n=90) or diagnosed with NAFLD (steatosis n=246; NASH=131). Analysis of around 700 serum metabolites (including amino acids, glycerolipids, phospholipids, sphingolipids, fatty acids, acyl carnitines and bile acids) was performed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS). "The analysis of this massive metabolomic information reveals", says José Mato from Biogune, "that NAFLD metabolic signature is dependent on the patients' body-mass index (BMI), indicating that the NAFLD pathogenesis mechanism may be quite different depending on the individual's level of obesity".

A BMI-stratified multivariate model based on the NAFLD serum metabolic signatures was generated to separate patients with and without NASH. This metabolome-based NASH predictor, which presently is commercialized by the Basque company OWL Genomics under the trademark owlliver, correctly established NASH in 94% of the patients.

Metabolomics

Metabolomics is a branch of "omics" research focused in the high-throughput identification and quantification of small sized (< 1500 Da) compounds. While in other "omics" fields, such as genomics, transcriptomics, and proteomics, thousands of targets are routinely identified and quantified at a time few studies have identified and/or quantified more than 30 metabolites simultaneously. Over 4,600 different compounds (http://www.serummetabolome.ca) have been identified in human serum, of which more than 75% are lipids being the majority phospholipids (over 2,000 different molecular species) and glycerolipids (over 1,000 different triglycerides and diglycerides). Using proprietary technology OWL Genomics, in collaboration with Biogune, has introduced the first in vitro serum based diagnostic for steatosis and NASH.

References for the study:

- Obesity dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. Journal of Proteome
J. Barr, J. Caballería, I. Martínez-Arranz, A. Domínguez-Díez, C. Alonso, J. Muntané, M. Pérez-Cormenzana, C. García-Monzón, R. Mayo, A. Martín-Duce, M. Romero-Gómez, O. Lo Iacono, J. Tordjman, R. J. Andrade, M. Pérez-Carreras, Y. Le Marchand-Bruste, A. Tran, C. Fernández-Escalante, E. Arévalo, M. García-Unzueta, K. Clement, J. Crespo, P. Gual, M. Gómez-Fleitas, M. L. Martínez-Chantar, A. Castro, S. C. Lu, M. Vázquez-Chantada, and J. M. Mato

CIC bioGUNE leads European researcher training project

Mon, 19 Mar 2012 23:00:00 GMT

- The Basque research Centre is coordinating UPStream, an excellence training programme for young scientists investigating the biochemical process of ubiquitylation and other related modifications

- The project, with allocated funding of 3.3 million euros, will train 12 young scientists studying biochemical processes related to diseases such as cancer or neurodegenerative diseases.

Training new generations of top scientists is one of the European Union's priorities. To this end, the European Commission funds Initial Training Networks (ITN), prestigious training programmes of excellence for young researchers within the Marie Curie People Programme, who will spearhead the scientific advances of the future.

The Centre for Cooperative Research in Biosciences CIC bioGUNE has been selected to lead one of them - the UPStream project, with an allocated funding of 3.3 million euros, focusing on specific training of 12 young scientists in the biochemical process of ubiquitylation and other related processes. The project will last 48 months and officially started last November. The student hired by CIC bioGUNE joined the team in January this year.

PhD students will be hired for three years by the 15 institutions that are taking part in this consortium, each one a benchmark in its field, including public research centres such as the Centre National de la Recherche Scientifique in France, the University of Frankfurt, and private companies such as the pharmaceutical multinational GlaxoSmithKline.

During this time, hired students will conduct their research in each one of the participating centres in the consortium, and they will also be able to take part in courses and visit laboratories in other participating centres. After 36 months, the young researchers will have enough skills to present their doctoral theses.

One of the key aspects of the project is the secondment of students for short periods to the other research centres that are participating in the UPStream network. The aim is to promote knowledge transfer between laboratories in the different centres, through the experience gained by the students.

Ubiquitin-dependent protein degradation

UPStream, coordinated by CIC bioGUNE researchers Manuel S. Rodríguez and Rosa Barrio, focuses on a critical and complex field in modern biology: understanding the regulation of post-transcriptional modifications and the ubiquitin-dependent protein degradation system (UPS, ubiquitin-proteasome system), and its potential application in drug development.

The biochemical process of ubiquitylation, as well as the modification by other ubiquitin-like proteins, involves attaching ubiquitin, SUMO or NEDD8, to a target protein, and is an efficient way of labelling proteins that will be degraded by the proteasome (protein degradation complex) or will change their interaction with other proteins according to the needs of the cell.

These processes regulate protein function or stability and hey are the centre of many biological processes of medical interest, such as cancer, ageing and neurodegenerative diseases.

According to Rosa Barrio, project co-coordinator, "the UPStream project has been supported by the Marie Curie programme and the consortium gathers some of the best labs in the world studying post-transcriptional modifications. It is very important for CIC bioGUNE to take part in the consortium next to these illustrious labs, and especially as coordinators. This allows us to network with other labs and institutions in Europe. We must take into account that only a limited number of ITN projects are awarded each year and that the labs and institutions that are taking part in this network are world renowned".

Ubiquitin Family Modifiers and the Proteasome

Sun, 18 Mar 2012 23:00:00 GMT

Researchers from Laboratory 3 at Proteomics Research Unit, have collaborated in the book "Ubiquitin Family Modifiers and the Proteasome" with the chapter titled "Isolation of Ubiquitylated Proteins Using Tandem Ubiquitin-Binding Entities".

About this book:

The ubiquitin-proteasome system (UPS) and ubiquitin-related modifiers are not only involved in cellular protein quality control but also in the regulation of many fundamental cellular processes/pathways as well as in their disease-relevant aberrations. Ubiquitin Family Modifiers and Proteasome: Reviews and Protocols presents both novel developments in UPS research and important methods related to the main recent advances in the field of ubiquitin family modifiers. Divided into five convenient sections, this volume focuses on the enzymology and substrate identification of ubiquitin family modifiers, the recognition and chain formation of these modifiers, the analysis of proteasome biogenesis and function, protein quality control, and finally the use of small molecules and strategies to study or manipulate the function of the UPS and of ubiquitin family modifiers, respectively. Written in the highly successful Methods in Molecular Biology^TM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls.

CIC bioGUNE participation in this book:

This book includes state of art protocols written by specialist in the field. A book to have in the laboratories exploring functions regulated by ubiquitin and ubiquitin-like molecules. The capture of ubiquitylated proteins using Tandem Affinity Binding Entities is a method developed by our group that allows the capture of endogenous proteins modified by ubiquitylation without the need to use tagged forms of proteins. Therefore our technology can be used extract these proteins from cell lines, tissues and organs from animal models or samples from patients. Ubiquitylated proteins can be analyzed by simple Western -blot or immunoprecipitation if the identity of the protein (s) of interest is known of by mass spectrometry if they have to be identified.

Book available here

Mad rabbit disease

Mon, 12 Mar 2012 23:00:00 GMT

- Our scientists have shown that rabbits, which were previously thought to be resistant to prion diseases, can also develop such infections.

- This research, led by Dr. Joaquín Castilla, has been published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS) and has resolved a mystery that has been studied for several decades.

- However, the authors of this study consider that an epidemic of mad rabbits similar to that seen in cows in the 1990s is highly unlikely.

(Bilbao, March 13th, 2012).- Rabbits have been considered to be resistant to prion disease for more than 40 years. This certainty was based on the experimental inoculations with prions from various sources to which this species was submitted, which proved to be negative. Furthermore, there is no evidence of transmissible spongiform encephalopathies in these animals in Nature, and no prion diseases have been diagnosed in any of the rabbits from those zoos that used feed contaminated with the agent known to cause this disease in cows, which is able to infect the majority of species in captivity.

All these findings appeared to confirm an exception to the rule that essentially all mammals could develop an infectious and transmissible prion disease. In other words...

Juan Manuel Falcón's conference

Tue, 06 Mar 2012 23:00:00 GMT

Juan Manuel Falcón will participate in the MS Technology Days organized by Waters Corporation between the days 20th and 21st of March that will take place in Madrid and Barcelona with the speach "Metabolomics as a Tool for Preclinical Studies".

Link to the program here.

Juan Manuel Falcón's conference

Wed, 29 Feb 2012 23:00:00 GMT

Juan Manuel Falcón has participated in the conference "Extracellular Microvesicles as Biological Source for Biomarker Discovery", organized by the Luxembourg Center for System Biology, University of Luxembourg the 29th of February and hosted by Karsten Killer and Rudi Balling.

Women and science

Sun, 26 Feb 2012 23:00:00 GMT

Our research, Edurne Berra, will participate in the fisrt edition of the conference "Women and science".

Valentine's PhD defence

Sun, 26 Feb 2012 23:00:00 GMT

Valentine Comaills will defend her PhD thesis, entitled "Retinoic acid and estrogen signalling pathways in tamoxifen resistant breast cancer cells", on March 2nd, at 13.00H. The event will take place in 'Salón de grados de la Facultad de Ciencias', at the University of Basque Country.

A prestigious American foundation will fund research at Biogune into Angelman Syndrome

Sun, 12 Feb 2012 23:00:00 GMT

The group led by Dr. Ugo Mayor aims to identify the protein substrates responsible for this genetic disorder by using a new strategy for capturing neuronal ubiquitin conjugates in the fruit fly.

The March of Dimes Foundation, which will provide 150,000 USD over two years, is a health-related, United States non-profit organisation whose goal is to improve infant health by preventing birth defects and infant mortality.

Angelman Syndrome is a rare disease that affects 1 out of every 15,000 newborns. Infants with AS present delayed development, limited language skills and poor motor coordination.

(Bilbao, 13 February 2012).- The prestigious American March of Dimes Foundation is to fund a research project at the Basque centre Biogune, led by Dr. Ugo Mayor, which aims to identify the protein substrates responsible for the Angelman Syndrome, a genetic disease that affects newborns, by using a new strategy for capturing neuronal ubiquitin conjugates in the fruit fly model system.

The March of Dimes Foundation is a health-related, United States non-profit organisation whose goal is to improve infant health by preventing birth defects and infant mortality. Founded in 1938, March of Dimes provides funding for research programmes, community services, education and promotion.

Mayor's research group at the Biogune bioscience research centre, located in the Bizkaia Technology Park, is devoted to studying the role played by a specific molecular mechanism known as ubiquitination in the development and functioning of the nervous system.

In their most recent paper, published in May 2011, the group reported the active presence of various proteins responsible for catalysing the incorporation of ubiquitin into the nervous system of the fruit fly, a model system which is widely used due to its genetic similarity to humans and having a relatively complex nervous system that is nevertheless fairly easy to study.

One of the proteins identified was found to be homologous to the product of the gene responsible for Angelman Syndrome (AS), a genetic disorder with a prevalence of approximately 1 out of every 15,000 newborns. Infants with AS present delayed development, limited language skills and poor motor coordination, as well as balance and movement problems. People affected with this syndrome also have a tendency to laugh frequently, present attitudes that transmit overwhelming happiness and have a high capacity for receptive, non-verbal communication.

First described in 1965, the cause of AS was subsequently identified in 1997 as the mutation of a gene known as UBE3A (located on chromosome 15q), which codes for an ubiquitin ligase that is responsible for binding ubiquitin molecules to other proteins.

In the opinion of the project leader, Dr. Ugo Mayor, "the substrate proteins modified by this ubiquitin ligase in the brain are still unknown, therefore their identification could help us to understand how the syndromes described come about".

In light of this, Mayor's team, which uses an experimental model that they consider to be suitable for solving this problem, decided to submit a project to the March of Dimes Foundation. The main goal of this project is to identify the substrates of the protein responsible for Angelman Syndrome using a new strategy for capturing neuronal ubiquitin conjugates in the fruit fly model system.

The March of Dimes Foundation will provide 150,000 dollars worth of funding for this research project over the next two years.

"It is plausible that, even when we finally identify the neuronal substrates of UBE3A, we will be unable to develop a treatment for Angelman Syndrome, but if even a small possibility exists, this will only become clear once we understand the molecular mechanisms associated with this disease", concludes Dr. Mayor.

For more information regarding neuronal ubiquitin pathways, browse to laboratory's website.

New therapeutic target to fight liver cancer discovered

Thu, 12 Jan 2012 23:00:00 GMT

Researchers from the Center for Cooperative Research in Biosciences, CIC bioGUNE (Bizkaia), led by Dr. Maria Luz Martínez Chantar, have found a close relationship between high levels of HuR protein and the malignancy of hepatocellular carcinoma through neddylation, a novel molecular process in the research of this pathology.

The study, which was published in the journal Hepatology, has obtained a special mention in the Cancer section of the prestigious journal Nature Reviews Gastroenterology&Hepatology.

This project opens new opportunities for the future development of potential personally-tailored therapeutic applications for the treatment of Hepatocellular Carcinoma.

(Bilbao 13 January 2012).- Hepatocellular carcinoma (HCC) is responsible for most cases of liver cancer; it is the fifth most common cancer in the world and the third cause of death after lung and gastric cancer. CHC is a bad prognosis tumour, even in developed countries. Its incidence is similar to its mortality rate, which means that most patients die within several months, despite diagnosis and therapeutic breakthroughs. It is a heterogeneous tumour and therefore the scientific community is doubling their efforts to establish very precise and personalised therapeutic targets.

A group of researchers of the Metabolomics Unit of CIC bioGUNE, led by Dr. Martinez Chantar, has taken a new step in the study of liver cancer, revealing the molecular mechanism, which was unknown until now, involved in the development of CHC. They observed how the malignancy of this disease may be related with overexpression of a protein, HuR.

The paper, which was published in the journal Hepatology, and that has obtained a special mention in the Cancer section of the prestigious journal Nature Reviews Gastroenterology & Hepatology, has revealed the relationship between overexpression of the protein HuR and the malignancy of Hepatocellular Carcinoma through a completely novel molecular mechanism called neddylation, which opens new opportunities for the future development of potential therapeutic applications. This new route is also applicable to colon cancer, due to the high correlation between both types of tumours.

"Neddylation is an enzymatic reaction that avoids protein degradation, in the biological context, of proteins that are modified by NEDD8 molecule. Just like ubiquitination marks proteins to be degraded, neddylation marks them to stabilise them. Therefore, we pose that these are key to tumour proliferation and development", explains Dr. María Luz Martínez Chantar, researcher at the Metabolomics Laboratory in bioGUNE and project leader.

In this sense, the strategy consisted on keeping the HuR at high expression levels modifying it by neddylation, thus promoting CHC proliferation and malignancy. Consequently, "when we block neddylation or regulate HuR protein levels in liver tumours and in vivo and in vitro hepatoma lines, cell death is induced leading to tumour regression", states Martínez Chantar.

Conventional oncological treatment options for Hepatocellular Carcinoma are limited, since it is a strong chemoresistant tumour, often developing in a cirrhotic liver. Around 40% of patients are diagnosed CHC at a late stage, and short-term prognosis is reserved (survival after 1 year in 29% of cases, and 2 years for 16%). This neoplasm is unique in Oncology, because in spite of its high incidence and bad prognosis, until recently an effective therapy had not been available. A possible explanation to this fact is the high heterogeneity of the molecular mechanisms involved in the development of this tumour.

The next step within this long and complex research process is to find a potential therapeutic application for the identified formula, for which Dr. Martínez Chantar, together with the pharmaceutical Millenium: The Takeda Oncology Company, will use new neddylation inhibitors marketed by the company and currently tested in other type of tumours, in "in vivo" Hepatocellular Carcinoma models (mice), exploring this new therapeutic solution.

"Now that we discovered that neddylation can play a key role in the development and progress of CHC, our next step is delving into a comprehensive study of its potential therapeutic applications" concludes Martínez Chantar.

References for the study:

- Mdm2 regulates HuR stability in human liver and colon cancer through neddylation.
Embade N, Fernández-Ramos D, Varela-Rey M, Beraza N, Sini M, de Juan VG, Woodhoo A, Martínez-López N, Rodríguez-Iruretagoyena B, Bustamante FJ, de la Hoz AB, Carracedo A, Xirodimas DP, Rodríguez MS, Lu SC, Mato JM, Martínez-Chantar ML.
Hepatology. 2011 Nov 16. doi: 10.1002/hep.24795. [Epub ahead of print]

- Cancer: Mdm2-regulated stabilization of HuR by neddylation in HCC and colon cancer-a possible target for therapy.
McLarnon A.
Nat Rev Gastroenterol Hepatol. 2011 Dec 13. doi: 10.1038/nrgastro.2011.241. [Epub ahead of print] No abstract available.
PMID: 22158377

External references:

Diario médico

El Pais (Ed. Pais Vasco)

El Correo

Arkaitz Carracedo: searching the keys of cancer

Tue, 10 Jan 2012 23:00:00 GMT

Small interview to one of our researchers in Teknopolis TV show

SAMe and HuR in Liver Physiology : Usefulness of Stem Cells in Hepatic Differentiation

Tue, 10 Jan 2012 23:00:00 GMT

Hepatic differentiation is a complex process that requires the balanced regulation of multiple pathways. Significant advances have been made in understanding the molecular mechanisms that modulate the onset of hepatogenesis, including the regulatory effect executed by S-Adenosyltmethionine (SAMe), which involves HuR function, recently reported by the Metabolomics Unit of CICbioGUNE (Vazquez-Chantada et al. 2010). Although this and other discoveries contributed to throw light into the tangle of regulatory mechanisms that govern this process, an overall understanding of their synchronicity and complementarity is still limited. Over the last years, this biological event was tried to be efficiently in vitro reproduced by priming embryonic stem cells, mesenchymal stem cells, liver progenitor cells or, more recently, induced-pluripotent stem cells towards a hepatocyte lineage and/or complete hepatocyte maturation by different combinations of growth factors and matrixes.

The interest on defining an efficient device that enables the specific hepatic fate of stem/progenitor cells is not only based on the usefulness for studying the molecular basis of hepatocyte differentiation per se but also on its potential to provide a continual source of liver cells for therapeutic and pharmaco-toxicological purposes.

The new book Methods in Molecular Biology; Liver Stem Cells reviews the role of a putative stem cell and liver-specific stem cell in regeneration and carcinogenesis and sums up the advantages and disadvantages of the different in vitro hepatic differentiation systems published to date, providing valuable protocols. These protocols in combination with the methods used in current days to elucidate cell signaling pathways described by Martinez-Chantar´s group, become this book on a gold standard on this topic, representing an attractive approach to uncover the underlying mechanisms that govern liver development.

Book available here

Molecular Machines in Biology

Tue, 20 Dec 2011 23:00:00 GMT

Mikel Valle and Xabier Agirrezabala have collaborated in the new book edited by Joachim Frank with the chapter entitled "Structure and dynamics of the ribosome as revealed by cryo-electron microscopy".

About the book:

The concept of molecular machines in biology has transformed the medical field in a profound way. Many essential processes that occur in the cell, including transcription, translation, protein folding and protein degradation, are all carried out by molecular machines. This volume focuses on important molecular machines whose architecture is known and whose functional principles have been established by tools of biophysical imaging (X-ray crystallography and cryo-electron microscopy) and fluorescence probing (single-molecule FRET). This edited volume includes contributions from prominent scientists and researchers who understand and have explored the structure and functions of these machines. This book is essential for students and professionals in the medical field who want to learn more about molecular machines.

Book available here

Bioinformatics for High Throughput Sequencing

Thu, 03 Nov 2011 23:00:00 GMT

Ana María Aransay and Naiara Rodríguez-Ezpeleta, with the collaboration of Michael Hackenberg, have published their new book, Bioinformatics for High Throughput Sequencing.

About the book

- The book looks at all aspects of next generation sequencing data analysis, and focuses on the practical issues.
- Guidelines are given for the analysis of the data obtained from each experiment.
- A close look at a rapidly expanding type of facility that will soon be available in almost every laboratory worldwide.

The ultimate goal of bioinformatics is to extract biological knowledge out of the large amount of information generated by the scientific community. The chapters compiled in this volume will allow both biologists and computer scientists to understand the significance and potential of this discipline in the analysis of high throughput sequencing data. An essential reference book, not only for serving as guideline for the comprehension of the main data analysis steps, but also for providing new insights into existing software and inspiration to develop new applications.

Book available here

2nd Health Innovation Conference: The value of prevention

Wed, 26 Oct 2011 22:00:00 GMT

The conference took place on Thursday 27 October, at the Basque Government's Health Office in Bilbao, and involved two debates - one on "Biomarkers for early diagnosis" and another on "Prevention: evidence and perspectives".

(Bilbao, 26 October 2011).- Scientific research experts, medical professionals and health managers have gathered today, 27 October, in Bilbao, as part of the 2nd Health Innovation Conference, with the aim of analysing the situation and future challenges of prevention.

The 2nd Health Innovation Conference is organised by entities such as the Spanish Foundation of Health Sciences, CIC bioGUNE, Tomás Pascual Institute and the Basque Regional Health Department. It took place last Thursday from 9 am to 2 pm, in the Assembly Hall at the Basque Regional Health Office (Alameda Rekalde 39).

The aim of the conference was to consider and debate about the value of prevention, from the point of view of researchers, managers and health professionals. In this sense, topics such as biomarkers for early diagnosis, results and evidence in this matter, as well as the future of prevention were covered.

The conference began at 9.30 am with presentations by Julián Pérez Gil, president of Osakidetza; Ricardo Martí Fluxá, president of the Tomás Pascual Institute; and José M Mato, president of CIC bioGUNE, CIC biomaGUNE and trustee of the Foundation of Health Sciences.

The event included two debates: the first one, "Biomarkers for early diagnosis", was moderated by Iñigo Aizpurua, Pharmacy deputy director for the Basque Government, with interventions by Jonathan Barr, head of Metabolomics Dept. at Owl Genomics, and Jose Asúa, head of Knowledge Management and Assessment for the Basque Government's Health Department.

The second debate took place from 12 to 2 pm, with the title, "Prevention: evidence and perspectives", and was moderated by Juan Goiria, president of the Academy of Medical Sciences of Bilbao. Speakers included Gonzalo Grandes, head of the Teaching Unit at the Family and Community Medicine Department of the Basque Government; Ramón Cisterna, head of the Microbiology Service in Basurto Hospital; and Santiago Esnaola, head of Epidemiological Analysis Service at the Directorate of Knowledge and Management of the Basque Government's Health and Consumption Department.

The event was closed by the deputy minister of Health of the Basque Government, Olga Rivera.

View programme on PDF: 2nd Health Innovation Conference: The value of prevention

2nd health innovation cycle

Mon, 17 Oct 2011 22:00:00 GMT

The second health innovation cycle, conducted by Fundación Ciencias de la Salud, will take place on the 27th of october, 2011.

Discovery of a cell mechanism that reduces effectiveness of breast cancer treatment

Sun, 09 Oct 2011 22:00:00 GMT

- Researchers from Massachusetts General Hospital, Harvard Medical School and CIC bioGUNE discover a complex cell mechanism activated by a protein - HOXB9 - that becomes an obstacle for radiation effectiveness.

- The study was recently published in Proceedings of the National Academy of Sciences (PNAS)

(Bilbao, October 2011).- Scientists all over the world continue to focus their research on breast cancer. As a consequence, knowledge of the behaviour of tumour cells is growing, as well as of their interactions with the microenvironment. There are, however, many questions still unanswered.

A new collaborative study carried out by the laboratory of Dr María Vivanco, researcher at the Cell Biology and Stem Cells Unit in the Center for Cooperative Research in Biosciences, CIC bioGUNE, and the groups led by Dr Zou and Dr Maheswaran in Boston, has provided insight into one of these mysteries: a cell mechanism that explains how a protein - called HOXB9 - helps cancer cells to avoid the attack of treatments such as radiation, and prevents the therapy from having the desired effect on certain types of breast cancer.

The study was recently published in Proceedings of the National Academy of Sciences (PNAS) The study shows that cells that express higher levels of the HOXB9 transcription factor are more likely to survive the radiation used as breast cancer treatment.

A complex mechanism induced by this protein has been discovered, which manages to activate a whole chain of cell processes in which different proteins - such as ATM kinase, amongst others - intervene, and which make certain cancerous cells more resistant to treatment. Dr Vivanco explains, "when the tumour is exposed to radiation it induces DNA damage - a phenomenon that results in formation of double-stranded DNA breaks - leading the cells to respond and try to repair the damage caused in the DNA using another mechanism - called the DNA damage response," by activating ATM kinase. In this way, the cell cycle is stopped and the DNA is repaired in order to maintain chromosome stability.

HOXB9 expression causes an increase in survival of cells that have been exposed to radiation. This higher resistance occurs because of the acceleration of response to radiation and its higher recovery capacity after DNA damage. On the other hand, reduction of the levels of this protein, leads to increased cell sensitivity to radiation. Furthermore, the growth factor TGFbeta (a HOXB9 target) is also involved. Therefore, HOXB9 facilitates DNA repair by activation of the TGFbeta signalling pathway, which elevates ATM phosphorylation, accelerates DNA damage response and radiation resistance.

The published research is the continuation of another study carried out last year by CIC bioGUNE, Massachusetts General Hospital and Harvard Medical School, which showed that this same protein (HOXB9) is overexpressed in breast cancer and that its expression levels are associated with high tumour grade.

News

The eBook "Bioinformatics for High Throughput Sequencing" is one of the highly accessed ones at Springer

Nanoparticles for controlled drug release

Ikerbasque y CIC bioGUNE convierten euskadi en un referente internacional en biociencias

Discovery of a gene involved in fatty liver disease

The great human protein 'encyclopaedia'

CIC bioGUNE researchers to take part in the Basque Network of Food Safety Experts

Novel designed molecules could stop colon cancer metastasis

Eight years of biosciences

Analía Núñez-O'Mara defends her PhD thesis on January 16th, 2013

A new path for the future generation of glucose-measuring biosensors

Famelab, el certamen internacional de monólogos científicos, llega a España

LKB1: Friend or foe?

A joint study between the CNIO and CIC bioGUNE identifies metabolomic biomarkers that could prove useful in preventive molecular medicine

Jevgenia Tamjar defends his PhD thesis on December 3th, 2012

David Fernández Ramos defends his PhD thesis on December 5th, 2012

Algunos de los retos pasados y futuros de la Virología Estructural

¿Podemos poner a dieta el cáncer?

Jornada de divulgación

CIC NETWORK reúne a representantes políticos para debatir sobre política científica

Forum on Scientific Policy this October 11th at 11:00am

II International Workshop held at CIC bioGUNE

First 1st Board Meeting of the UPStream Consortium organized by CIC bioGUNE in Bilbao

First symposium of leading Spanish scientists who use Drosophila in their biomedical studies

CIC bioGUNE y CIC biomaGUNE, dos centros, un objetivo

Iñigo Urkullu visita las instalaciones de CIC bioGUNE

Pubmed ratings place the CIC bioGUNE Animal Units work in the top 10

The therapeutic potential of cellular fat oxidation in bone-marrow transplants and breast cancer

Synthetic solutions to combat infections

Viruses find new ancestors

CIC bioGUNE to hold exosome expert meeting

When fat meets inflammation: NK cells are to blame

Ugo Mayor

New non-invasive test for fatty liver disease diagnosis developed

CIC bioGUNE leads European researcher training project

Ubiquitin Family Modifiers and the Proteasome

Mad rabbit disease

Juan Manuel Falcón's conference

Juan Manuel Falcón's conference

Women and science

Valentine's PhD defence

A prestigious American foundation will fund research at Biogune into Angelman Syndrome

New therapeutic target to fight liver cancer discovered

Arkaitz Carracedo: searching the keys of cancer

SAMe and HuR in Liver Physiology : Usefulness of Stem Cells in Hepatic Differentiation

Molecular Machines in Biology

Bioinformatics for High Throughput Sequencing

2nd Health Innovation Conference: The value of prevention

2nd health innovation cycle

Discovery of a cell mechanism that reduces effectiveness of breast cancer treatment

Pubmed ratings place the CIC bioGUNE Animal Units work in the top 10