Tools
Friday, 7th October, 2011, 11:00-12:00
New approaches for G protein-coupled receptor modulation
G protein-coupled receptors (GPCRs) are one of the most prevailing protein families in the human genome. GPCRs are receptors for sensory signals of external origin such as odors, pheromones, or tastes; and for endogenous signals such as neurotransmitters, (neuro)peptides, hormones, and others. These proteins are key in cell physiology, and their malfunction is commonly translated into pathological outcomes. Thus, GPCRs constitute one of the most attractive drug targets. In the ligand-free basal state, GPCRs exist in equilibrium of conformations, each stabilized by a network of intramolecular interactions. Ligand binding at the native (or orthosteric) site modulates receptor function by stabilizing new interaction networks and establishing new conformational equilibria. Activating ligands, or agonists, stabilize conformational changes in cytoplasmic domains that increase receptor signaling. Conversely, inverse agonists decrease the basal, agonist-independent level of signaling by stabilizing different conformational changes. In addition, ligand binding to an allosteric site (that is topographically distinct from the orthosteric site) might modulate the signalling of the orthosteric ligand. Positive allosteric modulators enhance the response of orthosteric agonists, while negative allosteric modulators decrease the effect. We will show, combining the latest information about GPCR structure with chemical synthesis, site-directed mutagenesis, biophysical experiments and computational modeling, how the binding of the ligand to the allosteric or orthosteric site influences this equilibrium of conformations.
Speaker: Dr. Leonardo Pardo. Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, UAB
Room Seminar Room “Xipre” 173.06 (PRBB – 1st Floor)
Wednesday, 7th September, 2011, 11:00-12:00
Assessment of peptide conformational features by computational methods and the design of peptidomimetics
Peptides are important mediators in the regulation of physiological processes of living organisms, exercising actions as agonists, antagonist or enzyme substrates and inhibitors. Moreover, they have also been successfully used as disruptors of protein-protein interactions. Unfortunately peptides exhibit a low pharmacological profile and small molecule peptidomimetics are helpful alternatives. The process of designing a peptidomimetic using computational methods goes through a deep understanding of the conformational profile of a peptide. These are flexible molecules with a large number of low energy conformations. In this talk I shall address the problem of conformational profile characterization and how this information can be used for peptidomimetic design.
Speaker: Juan Jesús Pérez EQ/UPC
Room Seminar room 173.06 - PRBB
Friday, 15th July, 2011, 11:00-12:00
NMR and metabolomic applications to the development of novel molecularly targeted antineoplastic agents
An increased understanding of the molecular etiology of cancer has enabled the development of novel therapies that are collectively referred to as molecularly targeted agents. Unlike the drugs used in conventional therapy, these agents are designed to specifically interfere with key molecular events that are responsible for the malignant phenotype. The challenges associated with the development of these novel targeted therapies are distinct from those faced in conventional chemotherapy. They include, among other factors, the need to obtain a detailed knowledge of the 3D architecture of the molecular targets, as very often these strategies rely on structure-based approaches. Furthermore, the successful application of these approaches requires the identification of biomarkers that enable a better understanding of the mechanism of action and the clinical effects of these agents, as well as facilitate the selection of patient populations that are most likely to benefit from the treatment. This presentation will review our current strategy to identify novel inhibitors, based on fragment-based screening and 3D structure determination, against protein targets involved in cell invasion and metastasis. This approach relies on the combination of NMR with other biochemical, biophysical and computational approaches. Metabolomics by NMR, a relatively new strategy for measuring the metabolic profile of biological samples, will also be reviewed. This methodology is extremely useful to perform comparative analysis of healthy and diseased individuals, information that can be used to identify disease biomarkers and stratify patients based on molecular subgroups.
Speaker: Dr. Antonio Pineda-Lucena-Centro de Investigación Príncipe Felipe, Valencia (Spain)
Room Seminar Room “Xipre” 173.06 (PRBB – 1st Floor)
Tuesday, 21th June, 2011
Course on Bioinformatics for Integrative Genomics
We are pleased to announce that registration for the Course on Bioinformatics for Integrative Genomics for June 21th- 22th at UPF facilities is now open.The course is organized by the Biomedical Genomics lab of GRIB (IMIM-UPF). The objective of the course is to provide theoretical and practical expertise in the field of bioinformatics for integrative genomics. Attendees will learn how to handle and analyze genomic data to answer specific questions using tools developed in the Biomedical Genomics lab: IntOGen, Gitools and Condel. Registration is free, but limited places available. We strongly recommend you to register asap. To register: send a CV and a motivation letter to Melquíades Calzado(mcalzado@imim.es).
Speaker: Biomedical Genomics lab of GRIB (IMIM-UPF)
Room UPF facilities
Friday, 3rd June, 2011, 11:00-12:00
Unravelling the complexity of molecular kinetics: states, pathways and experimental evidence
Simulations of the conformational equilibrium of macromolecules typically reveal a complex network of conformational states and transition rates between the states. In contrast, experimental results, such as dynamical fingerprints of macromolecules, often seem to indicate two- or three state kinetics. Markov state models, which are an efficient method to capture and summarize the information obtained from molecular simulation, can be used to predict these dynamical fingerprints and to reconcile experiment with simulation. In the first part of the lecture, I will given an overview of how to extract metastable states and dominant pathways from a given Markov model. Then, I will use a four-state model of a protein folding equilibrium to illustrate how dynamical fingerprints can be predicted from a given Markov model. From the equations of this method it becomes evident that (i) there might be no process which corresponds to the common notion of folding; (ii) often the experiment will be insensitive to some of the processes present in the system. These effects cause the difference in complexity between experimental and simulation results. Lastly, it is not only possible to predict dynamical fingerprints, but one can also use Markov models to design experiments to selectively measure specific processes. This will be demonstrated for a fluorescence quenching experiment of the MR121-G9-W peptide.
Speaker: Dr. Bettina Keller (Computational Molecular Biology, Freie Universität Berlin, Germany)
Room Seminar Room “Xipre” 173.06 (PRBB – 1st Floor)
Thursday, 26th May, 2011, 11:00
An integrative approach for epigenetic data analysis
"High-Throughput sequencing (HTS) has revolutionized the study of gene regulation and expression. However, there is a strong need for methods that facilitate the integration of multiple datasets to build predictive models. We present a computational framework to analyze and integrate epigenetic data, which allows the development of predictive models of gene regulation. Within this framework, we provide tools to carry out analysis of HTS data from DNA-protein binding, RNA-protein binding and RNA expression assays. In particular, we have developed a method that can effectively characterize significant changes in epigenetic patterns genome-wide, including promoters, enhancers and genic regions. Furthermore, we provide a tool for building predictive models based on Machine Learning (ML) from multiple datasets. Using the published datasets, we show that our ML methodology allows us to predict the expression change from chromatin properties with 95% accuracy. Additionally, our tools allow the integration of a variety of input datasets and the application of many different ML methods. We finally discuss how this computational framework can be applied to the study of the epigenetic changes in cancer."
Speaker: Eduardo Eyras - Computational Genomics, UPF
Room 473.10 PRBB
Tuesday, 24th May, 2011, 15:30
Improvements in computer simulations in biomedicine and how they are going on-line
Molecular simulations and biochemical kinetics modelling are among the most computing demanding problems in biomedicine. In this talk I will introduce several improvements our group has been developing in the last years, and how they have been applied to a variety of questions proposed by our fellow experimentalists. However, an increasing demand for simple and multiplatform bioinformatics and simulations methods to tackle a variety of problems in biomedicine exists. Thus, the natural move of a research group to make its software widely spread is to create web portals and web services that habilitate others to use its tools in an easy way. We will show the concept of Activ8 as an extremely simple to use and absolutely expandable platform for building computational protocols on-line. Examples of its use will range from research to training.
Speaker: Dr. Jordi Villà i Freixa
Room Sala d’actes, planta baixa, Àrea General HUVH
Tuesday, 24th May, 2011, 10:00 - 14:00
Integrative Biomedical Informatics
Jornada sobre patents en l'àmbit de la Biomedicina
En el marc de la Plataforma Tecnológica Española de Medicamentos Innovadores, copresidida per Ferran Sanz, director del Programa de Recerca en Informàtica Biomèdica de l'IMIM (Institut de Recerca Hospital del Mar), s'organitza el proper 24 de maig a l'Auditori del Parc de Recerca Biomèdica de Barcelona (PRBB), una Jornada sobre patents en l'àmbit de la biomedicina. Aquesta jornada està dirigida pel professor Pascual Segura, agent de la propietat industrial de la Universitat de Barcelona i director del seu centre de patents. L'objectiu de la Jornada és explicar la importància dels drets de propietat industrial, què es pot patentar i sota quines condicions, entre molts altres temes. La inscripció que és gratuïta podeu realitzar-la clicant aquí.
Speaker: Pascual Segura - Universitat de Barcelona
Room Auditori del PRBB
Friday, 6th May, 2011, 11:00
Thesis of Alice Ledda: “Distribution and evolution of short sequence tandem repeats in eukaryotic genomes”
We investigated the use of next generation sequencing data, from the 1000 Genomes Pilot Projects, to quantify microsatellite variability in the human population and discover putative new loci involved in trinucleotide repeat expansion diseases. We analysed microsatellites phylogenetic conservation to learn about the role of selection in shaping microsatellite evolution. The first study concluded that in vertebrate lineages amino acid tandem repeats were more conserved than similar sequences located in non-coding regions. This lead us to the conclusion that evolution was preserving repeats in protein-coding regions. In a second stage we analzed the conservation of microsatellites in different genomic regions, comparing them with the conservation of microsatellite in intergenic region. We concluded that selection was not preserving microsatellites only in exons but also in other genomic regions.
Room room Josep Marull, Dr. Aiguader 80.
Thursday, 5th May, 2011, 11:00 AM
Pyicos: a versatile toolbox for regulatory genomics"
A revolution is taking place in the study of gene regulation: High-throughput sequencing has become the basis of various techniques, like ChIP-Seq, RNA-Seq, CLIP-Seq, and new techniques evolve constantly. But do we need a new specialized tool to analyze each data type? Not necessarily! We propose Pyicos (http://sourceforge.net/projects/pyicos/), a generic tool that can adapt to various data types, by providing operations that are typically required for their manipulation and analysis. Pyicos is open-source and its input are genomic positions obtained from the mapper of choice. We show the high accuracy of Pyicos by comparing it to methods, specifically designed for the analysis of ChIP-Seq, RNA-Seq or CLIP-Seq data. With its flexibility and suitability for integration, Pyicos provides a convenient basis for the study of gene regulation.
Speaker: Sonja Althammer - Biomedical Informatics, UPF
Room 473.10_Aula
- Related links
- http://genome.prbb.cat/wordpress/
