Xavier Barril is visiting the PRBB this friday to give a seminar on the title topic.

Here it comes a short abstract of the talk:

The combination of increased availability of structural information, major boosts in computational power and methodological developments is
taking structure-based drug discovery to a higher level. I will present the main research lines of the group, focussing on the development of a new type of docking scoring functions and the elucidation of structure-kinetics relationships. Together with new experimental methods, these type of tools will enable the discovery of drugs with more diverse and effective mechanisms of action.

PRBB-CRG Seminar Reminder: Monday February 20: Nir Ben Tal, University of Tel Aviv, Israel

Today we will host the visit of Dr. Nir Ben Tal, from the Department of Biochemistry and Molecular Biology, The George S.Wise Faculty of Life Sciences, Tel Aviv University, Israel.

The seminar is included in the PRBB-CRG conference series and is open to everybody in the PRBB interested in the subject. It will be at 12 in the seminar room Marie Curie on the ground floor of the PRBB.

Seminar Title: “Human Copper transporter 1: Model Structure, functional dynamics and Selectivity”
Host: Dr.Jordi Villà-Freixa, GRIB, UPF

I reprduce here the original letter sent by Rafael Pulido, from the CIPF, where he explains the current loss of jobs at his institution. This is a warning on the starting to be dramatical situation of the Spanish research system, a system that has consolidated in the last decades as probably the most active in the South of Europe.

ERE EN EL CIPF DE VALENCIA

Estimados compañer@s,

Sorprendentemente, la mayor parte de los científicos españoles sigue sin saber que en el Centro de Investigación Príncipe Felipe (CIPF) de Valencia se ha puesto en marcha, hace dos semanas, un severísimo ERE (sí, leéis bien: un expediente de regulación de empleo) que va a dejar en la calle a más de 100 personas de este centro de investigación (entre personal científico y de apoyo). La causa aducida para el ERE es de tipo económico, debido principalmente a la reducción de más del 50% en el presupuesto de funcionamiento del CIPF, que procede de la Conselleria de Sanitat de la Generalitat Valenciana. El ERE presentado contempla el cierre de 16 laboratorios, 14 líneas de investigación y la mayoría de los servicios tecnológicos, lo que supone el despido de todo el personal científico de los grupos (sí, leéis bien: de todo el personal científico, incluidos los técnicos, becarios, investigadores principales…) y la cancelación y renuncia, por parte del CIPF, de todos los proyectos de esos grupos (sí, leéis bien: proyectos del MICINN, FIS, etc). El resto de laboratorios no se libra, y su personal también se reducirá drásticamente. En tales circunstancias, las agencias financiadoras ya han empezado a anunciar la retirada de las subvenciones de proyectos concedidas a los grupos, porque consideran que éstos no podrán llevar a cabo la investigación para la que fueron concedidos los proyectos. Por si fuera poco, en paralelo a este ERE se ha abierto otro expediente que contempla una reducción salarial, para los que se queden en el centro, de hasta el 60%. El CIPF, que aspiraba a ser el buque insignia de la investigación biomédica en la Comunidad Valenciana, se ha convertido en pocos años, gracias a una nefasta gestión y al abandono de las subvenciones por parte de la Generalitat, en el barco fantasma de la ciencia española. Es la primera vez que un ERE de tal magnitud se aplica a un centro de investigación en Europa, posiblemente en el mundo, y sus consecuencias para la investigación biomédica en España, y sobre todo en la Comunidad Valenciana, van a ser devastadoras. Recibís este correo porque creemos que toda la comunidad científica (investigadores, sociedades científicas, agencias financiadoras, etc) tiene que ser conocedora de esta situación. Por favor, difundid este mensaje en vuestra red de contactos científicos porque, sorprendentemente, la mayoría de los profesionales que hacen ciencia en España siguen sin estar informados del ERE del CIPF. Adjuntamos dos “pósters” (castellano e inglés) que también os animamos a difundir.
Podéis obtener fácilmente información sobre el ERE del CIPF en cualquier buscador, o accediendo a nuestro blog: http://concienciavalencia.blogspot.com

Un saludo

Rafael Pulido Investigador Jefe del Laboratorio de Biología Molecular del Cáncer del CIPF Presidente del Comité de Empresa del CIPF

The CBBL team has been awarded in the new edition of the “Marató de TV3” basic research projects call. The awarded project deals with the study of the modulation of microglia/macrophage response by targeting novel immune receptors regulating cell activation and phenotype, which will provide neuroprotection after acute CNS damage.

The role of the CBBL within the consortium is to bring knowledge in the computational modelling of the receptors and their interations with different types of ligands. The project is coordinated by Laia Acarín (Universitat Autònoma de Barcelona), and includes the groups of Carme Solà (CSIC), Joan Sayós (Vall d’Hebron Institut de Recerca) and Hugo Peluffo (Institut Pasteur, Montevideo), as well as the CBBL.

The “marató de TV3”, organized by the Catalan public broadcasting media, has established since 20 years ago as a reference charity in Catalonia and the South of Europe and represents a sublimation of the expectations the general public puts into scientific research of important biomedical problems. Despite the economical difficulties our country is suffering in the last few years, the response of the public to the call for funding is increasing every year, demonstrating a very proactive and cohesive society.

As public researchers we take this new challenge with renovated energy, and taking into account the individual contributions of many anonymous people we will put all our efforts to produce a succesful outcome of the project.

The project will be awarded during the official ceremony that will take place at the UAB on Wednesday, November 9th 2011.

Update: news on the event at the UPF newsletter.

At 11AM PRBB 28th October 2011

Protein kinases (PK) are one of the largest and most functionally diverse protein families and are involved in
most cellular pathways. PK malfunction is related to an important number of human diseases, such as cancer, diabetes and cardiovascular diseases. Thus, PK represent major targets for drug development.
Historically, drug discovery programs have been dominated by efforts to develop antagonists that compete for binding with endogenous ligands at orthosteric sites. However, allosteric drugs might offer several therapeutic advantages over traditional orthosteric ligands, including greater safety and/or selectivity.
Here, by combining of state-of-the-art computer simulations as well as spectroscopy, chemical and molecular biology approaches we study in great details complex allosteric effects in the pharmaceutically relevant Abl and FGFr kinases.
In Abl a shift of the SH2 domain from the C- to the N-terminus of the catalytic domain has been found to be involved in activation [1]. The allosteric mechanism, by which the SH2 domain induces conformational changes at the active site, is still debated. We have used elastic network models, normal mode analysis, molecular dynamics simulation and mutagenesis to gain insight into the interplay between the SH2 domain and the relevant motifs at the catalytic site. We propose a mechanism, by which the SH2 domain influences the dynamics of the crucial residues directly involved in the catalytic process. In FgFr we use free energy calculations, crystallography and NMR approaches to shed light on the mode of action of a novel allosteric inhibitor. [2]

[1] Nagar B, Hantschel O, Seeliger M, Davies JM, Weis WI, Superti-Furga G, Kuriyan J Molecular Cell 2006, 21, 787-798.
[2] F. Bono et al., submitted.

Date: 19th October 2011
Time: 12:00h
Place: Aula seminari de física fonamental (3.20)

Speaker: Jordan M. Horowitz (Departamento de Física Atómica, Molecular y Nuclear and GISC, Universidad Complutense de Madrid, Spain)

Title: Thermodynamics with Feedback: Extracting Work from Information

Abstract.-

The laws of thermodynamics restrict the maximum efficiency with which a thermodynamic engine can convert heat into useful work. However, this limit can be overcome with the use of feedback – that is by altering the operational protocol of the engine in response to information about its microscopic state. The reason being that the information acquired through feedback can itself be converted into work. In this talk, I will discuss recent results detailing how information enters into the thermodynamics of a system driven away from equilibrium by feedback, such as a thermodynamic engine. In particular, I will prove and analyze the second law of thermodynamics with discrete feedback, which relates information to heat, work, and irreversibility. We will see that optimal feedback processes that convert all the information into work are feedback reversible – they are indistinguishable from their time reverse. Finally building on the intuition gained from examining the second law of feedback, I will introduce a method for designing optimal thermodynamic engines with feedback, which I will illustrate with an N-particle Szilard engine.

Sagawa, T. and Ueda, M., Phys. Rev. Lett. 100, 080403 (2008)
Horowitz, J. M. and Vaikuntanathan, S., Phys. Rev. E 82, 061120 (2010)
Horowitz, J. M. and Parrondo, J. M. R., Eurphys. Lett. 95, 1005 (2011)

Omnis Cellula is a journal for scientific communication in the Catalan-speaking region, published by the Catalan Biological Society. A short note on the way computer simulations have provided clues on how enzymes work has recently appeared.