Wednesday, 23th October, 2013, 11:00

“Identification of cancer drivers across tumor types”

Thousands of tumor genomes/exomes are being sequenced as part of the International Cancer Genome Consortium (ICGC), The Cancer Genome Atlas (TCGA) and other initiatives. This opens the possibility to have, for the first time, a comprehensive picture of mutations, genes and pathways involved in the cancer phenotype across tumor types.

We have developed computational methods able to identify signals of positive selection in the pattern of tumor somatic mutations, which point to genes and pathways directly involved in the development of the tumors.

We have applied these approaches to 3025 tumors from 12 different cancer types of the TCGA Pan-Cancer project, identifying 291 high-confidence cancer driver genes acting on those tumors (Tamborero et al 2013).

We have also developed IntOGen-mutations (http://www.intogen.org/mutations), a novel web platform for cancer genomes interpretations, which analyses not only TCGA pan-cancer data but all mutation data from ICGC and other initiatives. The resource allows users to identify driver mutations, genes and pathways acting on more than 6000 tumors originated in 17 different cancer sites and to analyze newly sequence tumor genomes.

Among the novel cancer drivers identified there are chromatin regulatory factors and splicing factors, which are emerging as important genes in cancer development and are regarded as interesting candidates for novel targets for cancer treatment.

In my talk I will summarize all these recent findings.

References:

Tamborero et al., Comprehensive identification of mutations cancer driver genes across 12 tumor types. Scientific Reports 2013. 3:2650 doi:10.1038/srep02650

Gonzalez-Perez et al., IntOGen-mutations identifies cancer drivers across tumor types. Nature Methods 2013 doi:10.1038/nmeth.2642

Gonzalez-Perez et al., The mutational landscape of chromatin regulatory factors across 4623 tumor types. Genome Biology 2013 4(9):r106

Speaker: Núria López-Bigas, Biomedical Genomics, GRIB

Room Ramon y Cajal Room

Wednesday, 25th September, 2013, 11:00

Gut microbiotas in evolutionary studies: insights from cichlid fishes

With the advent of HT sequencing technologies we have just begun unveiling the genetic and functional diversity of gut microbial consortia, as well as their role in animal evolution. How does the gut microbiota evolve along the host lineages? Can the microbiota be considered as an inherited trait? And if so, is the microbiota a simple mirror or also a driver of the host evolution?

Both diet and host phylogeny are shown as crucial predictors of microbiota features, while the relative contribution of these two factors in recapitulating microbial communities relationships is currently under debate. Therefore closely related species that show a large differentiation of feeding habits represent an especially interesting system to investigate microbiota dynamics in response to concurrent host legacy constraints and selective pressures for rapid adaptation to different diet.

We are currently exploring specificity and dynamics of the gut microbiota in East African Cichlid fishes, which represent a large group of closely related species that underwent a spectacular dietary niche radiation. We recently profiled the gut microbiota of a young tribe of cichlids from lake Tanganyika that transitioned from a generalist feeding to a highly specialized diet primarily based on scales. How did the gut microbiota respond to such diet transition?

Speaker: Laura Baldo - Evolutionary Genomics. Biomedical Informatics, GRIB (IMIM - UPF)

Room Aula (473.10)

Tuesday, 17th September, 2013, 16:30

Unfolding diversity: Modeling promiscuity and toxicity in the metabolic space and beyond.

The development of in silico whole-cell model organisms is helping to build the interface between high-throughput biological data and predictive biology. I will present the work of our group based on metabolic circuits to design and optimize biological devices for production, sensing and regulation [1], introducing proof-of-concept applications of such devices for smart therapeutics and synthetic biology. Our approach is formally described through graph balance analysis, providing a methodology that can be used to study diverse coupling mechanisms such as promiscuous interactions [2] or toxicity pathways [3]. The integration of pathway information with whole-cell models might ultimately unveil unexpected synergistic effects originated from system perturbations.

[1] Carbonell P., Planson A.G., Fichera D., Faulon J.L. A retrosynthetic biology approach to metabolic pathway design for therapeutic production. BMC Systems Biology, 5:122, 2011.

[2] Carbonell P., Faulon J.L., Molecular signatures-based prediction of enzyme promiscuity. Bioinformatics, 26(16):2012-2019, 2010.

[3] Planson A.G., Carbonell P., Paillard E., Pollet N., Faulon J.L. Compound toxicity screening and structure-activity relationship modeling in Escherichia coli. Biotechnology and Bioengineering, 109:846-850, 2012.

Speaker: Pablo Carbonell, Institute of Systems and Synthetic Biology (iSSB), Univ. Evry, CNRS, Evry, France.

Room Charles Darwin (PRBB)

Thursday, 4th July, 2013, 11:00-12:00

Gold, protein and a ribosome: Simulating macromolecular encounters.

How do proteins recognise their diverse binding partners? How do they do this in the macromolecularly crowded and confined cellular environment? How do non-specific interactions affect protein motion and binding? We are developing molecular models and Brownian and molecular dynamics simulation procedures to address such questions [1-3]. I will discuss recent applications, including docking of an N-terminal processing enzyme to the ribosome [4], the binding of proteins to gold nanoparticles [5], and the simulation of protein diffusion and oligomerization in highly concentrated protein solutions [6,7].

[1] Gabdoulline, RR; Wade, RC. J. Am. Chem. Soc. (2009) 131, 9230-9238.

[2] Mereghetti, P. and Wade, R.C. J Phys Chem B. (2012) 116, 8523-33.

[3] Kokh, D.B., Corni, S., Winn, P.J., Hoefling, M., Gottschalk, K.,E., Wade, R.C. J.Chem. Theor. Comp. (2010) 6, 1753-68.

[4] Sankdikci, A., Gloge, F., Martinez, M., Mayer, M.P., Wade, R.C., Bukau, B., Kramer, G., Nat. Struct. Mol. Biol. (2013), in press.

[5] Brancolini, G., Kokh, D.B., Calzolai, L., Wade, R.C., Corni, S. ACS Nano. (2012), 6, 9863-78

[6] Mereghetti, P. and Wade, R.C. AIP Conf. Proc., (2013) 1518, 511.

[7] Balbo, J., Mereghetti, P., Herten, D-P, Wade, R.C.  Biophys. J., (2013) 104, 1576-84.

Speaker: Rebecca C. Wade, Heidelberg Institute for Theoretical Studies (HITS), and Zentrum für Molekulare Biologie (ZMBH), Heidelberg University, Germany

Room Xipre (seminar 173.06-183.01), PRBB.

Thursday, 27th June, 2013, 11:00-12:00

Visual phototransduction: from rhodopsin mutations to retinal disease

Rhodopsin is the visual pigment of the vertebrate retina responsible for light capture in the first molecular events of the complex process of vision. This photoreceptor protein has served as a prototypical model for G-protein coupled receptors (GPCRs) superfamily. Upon photoactivation, rhodopsin binds and activates the specific G- protein transducin. The details of this light-dependent activation, including the molecular interaction with transducin, have not been fully elucidated. Mutations in rhodopsin have been associated with the retinal degenerative disease retinitis pigmentosa (RP). The folding, degradation and aggregation of some of these mutant rhodopsins can be manipulated by drugs or molecular chaperones. Our goal is to deepen our knowledge of the molecular consequences of such mutations while gaining, at the same time, new insights into the structural requirements of the photoactivation process. We are also interested in the effect of lipids and metal ions on the structure, stability and function of rhodopsin, and the ligand protein interactions comparison between rhodopsin and cone opsin pigments. We will describe recent results on rhodopsin mutations associated to RP or potentially relevant for visual pigment evolution, the effect of docosohexaenoic acid lipid on the stability of purified rhodopsin and the kinetic differences between rhodopsin and red cone opsin ligand binding after photoactivation. Overall, our studies may enhance our understanding of the molecular mechanisms of phototransduction, the biology of GPCRs in general, and importantly, they may help develop potential approaches to treat RP caused by rhodopsin mutations.

(Supported by grants SAF2011-30216-C02-01 from MICINN, CIVP16A1861 from Fundación Ramón Areces, and Grups de Recerca Consolidats de la Generalitat de Catalunya (2009 SGR 1402).

Speaker: Pere Garriga, Department of Chemical Engineering, Universitat Politècnica de Catalunya (UPC)

Room Xipre (seminar 173.06-183.01), PRBB.

Tuesday, 18th June, 2013

Structure-Based Drug Design conference

BIO-IT, 19-21 June 2013, Cambridge, Massachusetts, USA.

Speaker: Gianni de Fabritiis

Sunday, 2nd June, 2013

Conference of the Russian Biophysical society

3-7 June 2013, Moscow, Russia.

Speaker: Gianni de Fabritiis

Wednesday, 29th May, 2013, 11:00

The isoform selection problem in genome-wide studies and its impact in alignment quality and positive selection

Speaker: Jose Luis Villanueva - Evolutionary Genomics (GRIB)

Room Aula (473.10)

Wednesday, 15th May, 2013, 11:00

Active intragenic enhancers and their effect in alternative transcription initiation

Speaker: Juan González-Vallinas, Evolutionary Genomics group, GRIB (IMIM-UPF)

Room Aula (473.10)

Sunday, 7th April, 2013

Conference of the american chemical society

8-11 April 2013 New Orleans,USA.

Speaker: Gianni de Fabritiis