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Seminars, events & talks

Tuesday, 24th May, 2011, 15:30

Computational Biochemistry

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

Friday, 1st April, 2011, 11:00-12:00

Computational Biochemistry

QM and MM Methods: Obtaining an Atomic and Electronic View of Nature

We will present our recent method development to map electronic and atomic coordinates for complex biological processes. 1) The atomic detailed mechanism of long range conformational changes remains a great challenge. Many biologically relevant processes, involving large domain motions or quaternary rearrangement, occur in the millisecond time scale, out of the reach of Molecular Dynamic techniques. PELE (Protein Energy Landscape Exploration), combines protein structure prediction techniques with a metropolis algorithm and is capable of fast mapping the slow motion energy landscape. 2) Electron transfer is one of the simplest but crucial reactions in biochemistry present in almost. Mixed quantum mechanics molecular mechanics methods (QMMM) offer a valuable computational tool for understanding the electron transfer pathway in protein-substrate and protein-protein complexes. By selectively turning on/off different residues in the quantum region, we have developed a novel approach capable of obtaining the electron pathway for short and large range interactions.
Short Cv. Past: PhD 1999 Autonomous University of Barcelona August 2000-August 2003, Postdoctoral Researcher, Columbia University Chemistry Department, New York City, NY (USA) August 2003- July 2006: Assistant Professor, Washington University in St. Louis, School of Medicine, Biochemistry & Molecular Biophysics (USA) Current: ICREA Professor, Life Science Department at the Barcelona Supercomputing Center and Adjunct Professor at Washington University in St. Louis (USA) Advice editor for Biophysical Chemistry, Elsevier Group.

Speaker: VíCTOR GUALLAR - ICREA - Barcelona Supercomputing Center

Room 473.10 PRBB

Monday, 4th October, 2010, 14h - 15h

Computational Biochemistry

Elements of Multiscale nonstandard simulation techniques (workshop on multiscale simulations - 2nd Barcelona School on Biomedical Informatics)

Standard mathematical models of complex dynamical biological processes include elements of ordinary differential equations to capture, for example, biochemical kinetics coupled with continuum partial differential equations models that represent spatial elements such as transport and motion. However, there is increasing interest in nonstandard simulation techniques that capture, for example, discrete stochastic subcellular behaviour or spatial heterogeneity in media via the concept of fractional derivatives. My challenge in 50 minutes is to give an overview of some of the important multiscale modeling and simulation issues associated with these nonstandard approaches.

Speaker: Kevin Burrage (Oxford University and QUT, Brisbane, Australia)

Room PRBB Auditorium

Monday, 4th October, 2010, 12h - 13h

Computational Biochemistry

How Local Network Oscillations lead to Functional Networks during Rest (workshop on multiscale simulations - 2nd Barcelona School on Biomedical Informatics)

Spatiotemporally organized spontaneous low-frequency (< 0.1 Hz) fluctuations have been revealed by the blood-oxygenation level-dependent (BOLD) fMRI signal during rest. Indeed, in the absence of a task, significant correlations between distinct anatomical regions are found. These correlations, referred to as functional connectivity (FC), yield large-scale maps constituting so-called resting-state networks (RSNs). Furthermore, direct measurements of the neuronal activity have revealed similar large-scale correlations, particularly in the slow fluctuations of the power of local field potential gamma frequency range oscillations. Nevertheless, the origin of this highly structured slow dynamics and its relationship with neural activity, particularly in the gamma frequency range, remains largely unknown. To address these questions, we defined a model of brain neural activity taking into account the long range connectivity together with their corresponding conduction delays and instantiating sustained gamma oscillations in the dynamics of its local nodes. We apply the model to the macaque and human measured structural connectivity. In the human case, we search for parameters such that the model best reproduces the human empirical FC obtained at the same nodes. The best agreement is found in a region of the parameter space where the network is globally in an incoherent state but where partial clusters of nodes tend to synchronize. Inside such clusters, the BOLD signal between nodes is found to be correlated, instantiating then RSNs. Between clusters, patterns of positive and negative correlations are found, as in experiments. These results are found to be robust to a number of model parameters.

Speaker: Gustavo Deco (Universitat Pompeu Fabra)

Room PRBB Auditorium

Monday, 4th October, 2010, 15h - 16h

Computational Biochemistry

Multimodel description of the human lungs (workshop on multiscale simulations - 2nd Barcelona School on Biomedical Informatics)

The respiratory system realizes the transfer of oxygen from the outside air to the alveolar membrane, through which it diffuses onto the blood. As pure diffusion is far from being sufficient to realize that transfer, most of it is of advective type, and this advection is triggered by inflation-deflation cycles of the paremchyma.
The mechanical part of the lungs can then be seen as a tree-like domain (conducting airways) embedded in an elastic medium. The flow in the upper part is inertial (incompressible Navier-Stokes equations), whereas inertia can be neglected for deeper branches (Stokes equations), which allows to use Poiseuille’s law for each branch, and consequently Darcy like equations on the corresponding subtrees. We aim at addressing the delicate issues in terms of theory, numerics, and modelling, raised by the coupling of those models (Navier-Stokes, Darcy equations on a network, elasticity equations).

Speaker: Bertrand Maury(Université Paris Sud)

Room PRBB Auditorium

Monday, 4th October, 2010, 16h - 17h

Computational Biochemistry

Multiscale modelling and simulation of drug-induced effects on the heart (workshop on multiscale simulations - 2nd Barcelona School on Biomedical Informatics)

In 1962, Denis Noble published the first mathematical model of a cardiac cell action potential based on the Hodgkin-Huxley formulation.
Since then, computational cardiac electrophysiology has developed into a mature discipline in which advanced computational, mathematical and engineering techniques are used to investigate heart rhythm mechanisms in health and disease.
The causes of cardiac arrhythmias are numerous and include disease, mutations and also drug-induced abnormalities in ionic properties. Of particular concern for regulatory agencies, pharmaceutical industry and society is the fact that certain drugs, in particular those not designed to affect the heart, can exhibit cardio-toxicity (i.e. unwanted side effects), which can put patients with otherwise healthy hearts at risk of developing lethal arrhythmias. In this presentation, we will describe the state-of-the-art in multiscale modelling and simulation of ventricular electrophysiology,and we will illustrate their use in the investigation of drug-induced abnormalities in heart rhythm mechanisms. The ultimate goal of the research described here is to contribute to the improvement of the diagnosis and treatment of cardiac arrhythmias to reduce the burden
they impose to society.

Speaker: Blanca Rodríguez (Oxford University)

Room PRBB Auditorium

Monday, 4th October, 2010, 11h - 12h

Computational Biochemistry

Multiscale modelling and simulation, lessons learned from COAST (workshop on multiscale simulations - 2nd Barcelona School on Biomedical Informatics)

A few years ago, within the COAST project, we started to develop a multiscale model of a challenging VPH application, namely in-stent restenosis (ISR). This resulted in a multiscale modelling paradigm that we coined Complex Automata (CxA). CxA models can be implemented using our Multiscale Coupling Library and Environment (MUSCLE). I will introduce the main ideas behind CxA, propose a taxonomy of multiscale models, and try to indicate the lessons learned for VPH type of applications. Multiscale modelling is one thing, but actually executing your multiscale models on computers is quite another ball game. I will show the example of a MUSCLE implementation of a simplified multiscale model for in-stent restenosis. Tightly coupled three dimensional multiscale models will usually require computing power beyond the desktop. This gave rise to the paradigm of Distributed Multiscale Computing, which is currently under development in the MAPPER project.

Speaker: Alfons Hoekstra (University of Amsterdam)

Room PRBB Auditorium

Monday, 4th October, 2010, 17h - 18h

Computational Biochemistry

The development of computational frameworks to explore the role of the pulsatile haemodynamic environment on the development of cerebral aneurysms for patient-specific arterial geometries (2nd Barcelona School on Biomedical Informatics)

The formation of a cerebral aneurysm is a complex mechanobiological process which is not yet clearly understood. However, the mechanisms that give rise to its development involve the complex interplay between the local mechanical stimuli acting on the arterial wall and the biological processes occurring at the cellular level. The inner surface of the artery is comprised of endothelial cells (ECs). Wall shear stress (WSS) is sensed by the EC and transduced into biochemical signals which activate signalling pathways to control its functionality and the functionality of the artery. The structure of the artery is continually maintained by fibroblasts and vascular smooth muscle cells. These cells secrete connective tissue and matrix degrading enzymes and may up/down-regulate expression levels in response to deviations of mechanical stimuli, e.g. their state of loading from normotensive levels. Recently, Watton et al (2009a, 2010) proposed a framework to couple the evolution of a saccular cerebral aneurysm to the haemodynamic environment. Briefly: the model utilises a realistic constitutive model of the arterial wall and links elastin degradation to deviations of WSS and spatial WSS gradients from normotensive levels; collagen remodels to maintain an equilibrium level of strain and the mass of collagen adapts to simulate fibroblasts responding to deviations of stretch from normotensive levels. However, the model considered idealised arterial geometries and linked arterial growth and remodelling (G&R) to steady flow parameters. In this study we extend the framework to patient-specific arterial geometries and link arterial G&R to mechanical stimuli that arise due to the pulsatile nature of the blood flow. A patient-specific cerebral aneurysm case is identified from clinical imaging data. The imaging data of the cerebral vasculature is automatically segmented and the geometry is subsequently manipulated with ANSYS ICEM: the aneurysm (located on the right internal carotid sinus artery) is removed and replaced by a short cylindrical section which is reconnected to the upstream and downstream arterial sections so that the surface gradients are continuous. It is within this inserted section, hereon referred to as “aneurysmal section”, that the formation of a new aneurysm is simulated. A rigid-wall approach is adopted to solve the pulsatile flow using physiological boundary conditions for the right internal carotid, and middle/anterior cerebral arteries. This enables G&R of the aneurysmal section to be explicitly linked to physiologically realistic haemodynamic stimuli. In addition, a quasi-static approach is used to obtain the geometry of the aneurysmal section at systolic and diastolic pressures, enabling G&R to be explicitly linked to the magnitude of the cyclic deformation of vascular cells. This is the first patient-specific model of cerebral aneurysm evolution that incorporates a realistic constitutive model of the arterial wall and explicitly links G&R to the pulsatile mechanical environment.

The framework provides the basis for further investigating and elucidating the aetiology of the disease. Further sophistications are required. For example, one natural development would be to model the signaling pathways linking the functionality of the cells to the mechanical and chemical environment. Such models could be integrated into conceptual models of aneurysm development (Watton et al 2009b) prior to integration into more sophisticated computational frameworks (Watton et al (2010)).

Speaker: Paul Watton (Oxford University)

Room PRBB Auditorium

Monday, 4th October, 2010, 9.30h - 10.30h

Computational Biochemistry

What is a model, and why not? (workshop on multiscale simulations - 2nd Barcelona School on Biomedical Informatics)

Indiscriminate use of terminology can be counter-productive for formation of concepts and their communication. Questions such as “What is a model?” or “What is a system?” will raise a multitude of answers, when posed to different people. This lecture aims to propose some common ground and a few basic definitions, from which answers to follow-on questions, such as “What is the best model of … [insert system of your choice]?” or “How soon will we have a complete model of …?” will emerge naturally. It will go on to discuss the multi-scale nature of modelling in bio(-medical) research, illustrate scenarios using the example of research into cardiac electro-mechanical interactions, and end with a praise of failure as the key driver of intellectual insight.

Speaker: Peter Kohl (University of Oxford)

Room PRBB Auditorium

Thursday, 5th March, 2009, 11:00

Computational Biochemistry

ByoDyn, analysing dynamics of biochemical networks

Speaker: Adrian Lopez - Computational Biochemistry and Biophysics, GRIB, UPF

Room room 473.10-PRBB

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