IRB Barcelona - NEWS

IRB Barcelona receives 20% of the ERC Advanced Grants awarded in Spain

irbbarcelona.org — Tue, 24 Jan 2012 12:00:00 +0100

Professors Cayetano González, Angel R. Nebreda and Modesto Orozco have each been awarded an ERC Advanced Grant, the first two in the category of Life Sciences and the last one in Physical Sciences and Engineering.

Only 13% of European researchers who have presented a project in the 2011 call passed the screening process.

Each project will receive funding of approx. 2.5 million euros over five years.

The European Research Council (ERC) has awarded three ERC Advanced Grants to the Institute for Research in Biomedicine (IRB Barcelona), which account for 20% of the 15 grants awarded to centres in Spain, according to information provided by the European research organisation. Likewise, the ERC statistics for the 2011 call reveal that of the 2284 projects presented, 294 passed the screening process, which represents a success rate of 13%. Advanced Grants are the most competitive in Europe both in terms of funding and in terms of the reduced number of consolidated European researchers able to achieve one. Another favourable piece of information for the centre is that it has had a 100% success rate, presenting three projects and receiving funding for all three.

Drs. Cayetano González and Angel R. Nebreda, ICREA professors at IRB Barcelona, will address the projects focused on cancer, “FliesCan” and “p38Cancer” respectively. These projects fall into the Life Sciences category. In contrast, “SimDNA”, the project presented by Dr. Modesto Orozco, full professor at the University of Barcelona, addresses the computational simulation of nucleic acids and is included in the Physical Sicences and Engineering category.

Tumours modelled on the fruit fly

In the project “FliesCan” –acronym of “Modelling Cancer Traits in Drosophila”-, the Cell Division Lab headed by Dr. Cayetano González will study tumour growth and aneuploidies (incorrect distribution of chromosomes during cell division). Dr. González will use the brain tumour development model in Drosophila melanogaster flies, a field in which he has contributed with seminal works in Nature, Dev Cell and Science. In spite of their anatomical and physiological differences, solid tumours in humans and flies show the same behaviour: they are caused by cells that break away from the normal process; they show uncontrolled growth; they become immortal; they are invasive; and they eventually kill the host. Given that the Drosophila fly is easy to use in the lab and its genetics are widely documented, it is an efficient model with which to study the malignant characteristics of human tumours. The “FliesCan” project has a double objective: to identify new ways by which to inhibit tumour growth and to determine the origin and function of aneuploidies and changes in the number of gene copies in tumour growth. The evaluation panel has also highly rated the great transfer potential of the project’s results to clinical practice as “FliesCan” includes the screening of drugs with possible therapeutic value.

P38 during tumor development

Dr. Angel Nebreda is an international authority on the p38 protein kinase family, which he co-discovered in 1994. These proteins acts as cell signal transmitters and they affect the activities of many other proteins and control highly complex processes that determine cell behaviour. Over a long career, Dr. Nebreda, head of the Signalling and Cell Cycle Lab at IRB Barcelona, has demonstrated the link between p38 and various kinds of cancer in successive articles in high impact journals. The “P38Cancer” project seeks to unravel the role of p38 in the development of tumours. The project combines studies in biochemistry and cancer cell biology, pharmacology, and genetic analyses. In summary, “p38Cancer” will address the key issues in cell signalling that control tumour growth, with the goal to contribute to a more rational development of cancer treatment.

The SimDNA project

The full name of Dr. Orozco’s project is “Advanced multiscale simulation of DNA”. SimDNA comprises three parts: the development of theoretical models and algorithms for computational simulations at several scales of resolution; the implementation of computational programmes; and the experimental validation of the predictions. The objective is to provide information about the structure and physical properties of nucleic acids and how these features explain the function of these molecules. Through SimDNA, the international scientific community will be provided with a series of computational tools that will unravel the behaviour of nucleic acids. The most direct application is in the field gene expression regulation and in epigenetics. In other words, the tools developed in the SimDNA project will allow scientists to fully understand the mechanisms that control gene expression.

BRIEF BIOGRAPHIES

Cayetano González (Madrid, 1957) received his PhD in Biology from the “Universidad Autónoma de Madrid”. He did his postdoctoral studies at the “Centro de Biología Molecular Severo Ochoa” in Madrid and at the David Glover laboratory at the Imperial College of London, University of Cambridge. During this time he focused his research on cell cycle regulation using the Drosophila melanogaster, a field in which he has contributed with seminal works in Nature, Dev Cell and Science. After four years as principal co-investigator at Dundee University, in Scotland, in 1994 he set up his own lab at the European Molecular Biology Laboratory, in Heidelberg. While in Germany he started his research into the relation between asymmetrical stem cell division and tumour growth. In 2004, after a year at the CNIO, he moved his lab to IRB Barcelona, where he has extended his cancer studies by modelling tumours in Drosophila. His contributions to all these fields are recognised worldwide, and most of his publications over the last ten years figure in the F1000, an association of scientists that compile rankings for articles. Also, his articles have been the focus of comments and reviews in several scientific journals. He holds two patents and has co-founded two Biotech enterprises, Cellzome (in Heidelberg) and EnVivo Pharmaceuticals (in Boston). He is a member of EMBO and of the editorial committee of several scientific journals and international financing agencies.

Angel Rodríguez Nebreda (Benavente, Zamora) studied Biology at the University of Salamanca and earned his PhD in 1986 from the same university. In 1987, he moved to the USA, where he did a 4-year post-doctoral stage at the National Institutes of Health. In 1992 he returned to Europe to join the group headed by Tim Hunt, 2001 Nobel Laureate in Medicine, at the Cancer Research UK Clare Hall Laboratories, in the UK. He set up his own group at the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany) in 1995. Nine years later, in 2004, Nebreda joined CNIO, and as of July 2011 he forms part of the critical mass of researchers at IRB Barcelona, where he is BBVA Foundation Cancer Research Professor. He is the author of more than 120 publications in leading scientific journals and 2 patents. Furthermore, he has directed 12 doctoral theses. He co-founded the biotech company Cellzome. He was elected an EMBO member in 2003 and has been the editor of the FEBS Letters and Biochemical Journal. He has served on the scientific advisory committees of several organisations, including the Association for International Cancer Research (AICR).

Modesto Orozco heads the Molecular Modelling and Bioinformatics group at IRB Barcelona. He is a senior professor in Biochemistry and Molecular Biology at the University of Barcelona, director of the Life Sciences Department at the Barcelona Supercomputing Center (BSC), director of the Joint IRB Barcelona/BSC Computational Biology Programme, and director of the Structural Biology node of the Instituto Nacional de Bioinformática (INB).

Dr. Orozco is a European leader in the simulation of biological systems and an international authority in the theoretical study of macromolecular systems, especially nucleic acids (DNA and RNA). During his career he has published more than 300 scientific articles and developed a series of computational programmes and algorithms that are used by the scientific community worldwide. His articles have received about 9,000 citations with an elevated impact factor, as reflected by a Hirsch index of 51, thus positioning him as one of the most visible chemists and computational biologists in the world. Dr. Orozco is an editor and editorial member of the most prestigious international scientific journals in his field of expertise. He has also served or is serving on several evaluation panels in Spain, Europe and the United States and he is an external consultant to a number of pharmaceutical companies. Dr. Orozco’s research has been awarded various national and international prizes and receives funding from the Marcelino Botín Foundation.

Better than the natural hormone

irbbarcelona.org — Fri, 20 Jan 2012 12:00:00 +0100

Researchers at IRB Barcelona synthesize an analogue of somatostatin that shows greater stability in blood and is more selective than the natural hormone. This compound could compete with the somatostatin analogues currently used in the treatment of certain kinds of cancer and other diseases.

For several decades the pharmaceutical industry has been interested in achieving peptide analogues —similar molecules with improved properties— of the natural hormone somatostatin. This hormone and another two analogue compounds, octreotide and lanreotide, are used for the treatment of several kinds of neoplasia, such cancer of the thyroid, pancreas and prostate, in diseases associated with the growth hormone, for example in gigantism, and in digestive hemorrhages. Headed by Antoni Riera (University of Barcelona) and Maria Macias (ICREA Research Professor), a team of researchers at IRB Barcelona, in collaboration with the company BCN Peptides, has designed a peptide that is ten times more stable in blood than the natural hormone and is more active than the two analogues currently available on the market. The success of the design lies in the substitution of two sequences in the natural sequence for two non-natural amino acids. Angewandte Chemie, the second highest ranking journal in chemistry, has published the article in the advanced online edition and has selected it for the inside cover in the first issue of February.

“The use of the natural hormone has two disadvantages: it degrades rapidly in the organism (2-3 minutes) and it has a wide spectrum of activities. Thus when attempting to correct certain diseases without affecting the normal function activated by the natural hormone, it is important to develop compounds that show greater stability in blood and that are more selective in their action. What we have obtained in the lab is a peptide that fulfills these two objectives”, explains Antoni Riera, head of the Asymmetric Synthesis Lab oratory at IRB Barcelona, where the new compound has been synthesized. “Also, it could be developed into a drug rapidly because this type of molecule does not usually cause toxicity”, the scientist adds.

The study performed by Drs. Riera and Macias also provides for the first time structural data on the many conformations of the natural hormone somatostatin. The hormone adapts its structure depending on the function that it performs, which is determined by its interaction with distinct receptors (five receptors have been characterized to date). These multiple conformations make it impossible to obtain a single structure for somatostatin either in solution or using X-ray diffraction techniques. “Through the resolution of the structure of the compounds synthesized and comparison with data on the natural hormone”, explains Maria Macias, head of the Protein NMR Spectroscopy Laboratory, “we have unraveled one of the active conformations of somatostatin in its interactions with one of the receptors, specifically SSTR2”. For the authors of the study, it has been both the innovative chemical synthesis of the molecule and the new structural approach combined with functional assays that have allowed a more rational design of analogues of the natural hormone. According to these researchers, this study opens the way for further designs of analogues that would be selective in their interaction with other receptors.

The first author of the article is Pablo Martín–Gago, a PhD student at IRB Barcelona, and the study has involved ten other researchers, among these three from the company BCN Peptides and three from the University of Alcalá de Henares.

Reference article

Fine-tuning the π-π Aromatic Interactions in Peptides: Somatostatin Analogues Containing Mesityl Alanine.

Martín-Gago P, Gomez-Caminals M, Ramón R, Verdaguer X, Martin-Malpartida P, Aragón E, Fernández-Carneado J, Ponsati B, López-Ruiz P, Cortes MA, Colás B, Macias MJ, Riera A.

Angew Chem Int Ed Engl. 2012 Jan 5. doi: 10.1002/anie.201108928. [Epub ahead of print]

Project to develop a new treatment for brain cancer

irbbarcelona.org — Thu, 12 Jan 2012 12:00:00 +0100

The “Generalitat de Catalunya” awards funds to a research on glioblastomas conducted by VHIO and IRB Barcelona.

A collaborative project run by the Institute for Research in Biomedicine (IRB Barcelona) and Vall d’Hebron Institute of Oncology (VHIO) has received one of the funding concessions of the first call of the “Prova’t” programme, promoted by the “Generalitat de Catalunya” (Autonomous Government of Catalonia). “Prova’t” seeks to boost the transfer of results from research centres in Catalonia to the productive sector.

The project will develop a new therapeutic strategy for glioblastoma, a very aggressive type of brain cancer with poor prognosis. This research involves the work of scientists Meritxell Teixidó and Ernest Giralt, at IRB Barcelona, and Joan Seoane at VHIO.

“Prova’t” is promoted by the “Institució dels Centres de Recerca de Catalunya” (CERCA), an organisation affiliated to the Department of Economy and Knowledge, with the support of the Secretary for Universities and Research. In this first call, CERCA will assign a total of 1.5 million euros to seven research projects.

Link to the PR issue by the "Generalitat de Catalunya" (in Catalan language)

Link to Ernest Giralt lab

Link to Joan Seone lab at VHIO