Research

 

Research Outline

Protein-protein interactions play a relevant role among the different functions of a cell. Identifying the protein-protein interaction network of a given organism (interactome) is useful to shed light on the key molecular mechanisms within a biological system. A paradox in protein-protein binding is to explain how the unbound proteins of a binary complex recognize each other among a large population within a cell and how they find their best docking interface in a short time-scale. We interrogate protein structure to unveil its function, generate the network of interactions and to relate genes/proteins with diseases by means of exploiting the topology of the network.


Current Projects

On the study of the relationship between sequence, structure and function of proteins: Characterization of the structural motifs involved in the function and interactions between proteins. Development of statistical potentials and analysis of physico-chemical potentials helping to describe the fold and function of proteins and its interactions with other macro-molecules.


On the prediction of protein-protein and protein-DNA interactions: Structural analysis of docking approaches and development of new techniques towards the prediction of binding sites and the mechanisms of interface selection of protein-protein and protein-DNA interactions.

On the analysis of protein interaction networks and its use on bio-medicine, helping to detect potential targets and prioritization of candidate disease-genes. Development of methods to study and integrate information for different types of networks and application on the study of metastasis. Prediction of signalling networks, such as the phosphorylation network and other post-transcriptional modifications, and integration with genomic data, such as microarrays.


Selected publications 2012-2016

  • Wright RH, Castellano G, Bonet J, Le Dily F, Font-Mateu J, Ballaré C, Nacht AS, Soronellas D, Oliva B, Beato M. CDK2-dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cells. Genes Dev, 2012; 26(17):1972-83
  • Garcia-Garcia J, Schleker S, Klein-Seetharaman J, Oliva B. BIPS: BIANA Interolog Prediction Server. A tool for protein-protein interaction inference Nucleic Acids Res, 2012; 40 (W1):W147-W151
  • Guney E, Oliva B. Exploiting Protein-Protein Interaction Networks for Genome-Wide Disease-Gene Prioritization. PLoS One, 2012, 7 (9) e43557
  • Santana-Codina N, Carretero R, Sanz-Pamplona R, Cabrera T, Guney E, Oliva B, Clezardin P, Olarte OE, Loza-Alvarez P, Méndez-Lucas A, Perales JC, Sierra A. A transcriptome-proteome integrated network identifies ERp57 as a hub that mediates bone metastasis. Mol Cell Proteomics, 2013; 12(8): 2111-2125
  • Planas-Iglesias J, Bonet J, García-García J, Marín-López MA, Feliu E, Oliva B. Understanding protein-protein interactions using local structural features. J Mol Biol, 2013; 425 (7):1210-1224
  • Bonet, J, Planas-Iglesias, J, Garcia-Garcia, J, Marin-Lopez,MA, Fernandez-Fuentes, N., Oliva, B. ArchDB 2014: structural classification of loops in proteins. Nucleic Acids Research, 2014; 42(Database issue):D315-9
  • Guney, E., Garcia-Garcia,J, Oliva, B. GUILDify: a web server for phenotypic characterization of genes through biological data integration and network-based prioritization algorithms. Bioinformatics 2014;30(12):1789-90
  • Oliva,B. & Fernandez-Fuentes, N. Knowledge-based modeling of peptides at protein interfaces: PiPreD. Bioinformatics. 2015; 31(9): 1405-10
  • Hill Sm, Heiser Lm, Cokelaer T, Unger M, Nesser Nk, Carlin De, Zhang Y, Sokolov A, Paull Eo, Wong Ck, Graim K, Bivol A, Wang H, Zhu F, Afsari B, Danilova Lv, Favorov Av, Lee Ws, Taylor D, Hu Cw, Long Bl, Noren Dp, Bisberg Aj; Hpn-Dream Consortium, Mills Gb, Gray Jw, Kellen M, Norman T, Friend S, Qutub Aa, Fertig Ej, Guan Y, Song M, Stuart Jm, Spellman Pt, Koeppl H, Stolovitzky G, Saez-Rodriguez J, Mukherjee S. Et Al. Inferring causal molecular networks: empirical assessment through a community-based effort. Nat Methods. 13(4):310-8. (2016)
  • Wright Rh, Lioutas A, Le Dily F, Soronellas D, Pohl A, Bonet J, Nacht As, Samino S, Font-Mateu J, Vicent Gp, Wierer M, Trabado Ma, Schelhorn C, Carolis C, Macias Mj, Yanes O, Oliva B, Beato M. ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling. Science. 352(6290):1221-5 (2016)
  • Poglayen D, Marín-López Ma, Bonet J, Fornes O, Garcia-Garcia J, Planas-Iglesias J, Segura J, Oliva B, Fernandez-Fuentes N. InteractoMIX: a suite of computational tools to exploit interactomes in biological and clinical research. Biochem Soc Trans. Jun 15;44(3):917-24. (2016)
  • Alvarez-Cienfuegos A, Nuñez-Prado N, Compte M, Cuesta Am, Blanco-Toribio A, Harwood Sl, Villate M, Merino N, Bonet J, Navarro R, Muñoz-Briones C, Sørensen Km, Mølgaard K, Oliva B, Sanz L, Blanco Fj, Alvarez-Vallina L. Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains. Sci Rep. 6:28643. ( 2016)
  • Sieberts Sk, Zhu F, García-García J, Stahl E, Pratap A, Pandey G, Pappas D, Aguilar D, Anton B, Bonet J, Eksi R, Fornés O, Guney E, Li H, Marín Ma, Panwar B, Planas-Iglesias J, Poglayen D, Cui J, Falcao Ao, Suver C, Hoff B, Balagurusamy Vs, Dillenberger D, Neto Ec, Norman T, Aittokallio T, Ammad-Ud-Din M, Azencott Ca, Bellón V, Boeva V, Bunte K, Chheda H, Cheng L, Corander J, Dumontier M, Goldenberg A, Gopalacharyulu P, Hajiloo M, Hidru D, Jaiswal A, Kaski S, Khalfaoui B, Khan Sa, Kramer Er, Marttinen P, Mezlini Am, Molparia B, Pirinen M, Saarela J, Samwald M, Stoven V, Tang H, Tang J, Torkamani A, Vert Jp, Wang B, Wang T, Wennerberg K, Wineinger Ne, Xiao G, Xie Y, Yeung R, Zhan X, Zhao C; Members Of The Rheumatoid Arthritis Challenge Consortium, Greenberg J, Kremer J, Michaud K, Barton A, Coenen M, Mariette X, Miceli C, Shadick N, Weinblatt M, De Vries N, Tak Pp, Gerlag D, Huizinga Tw, Kurreeman F, Allaart Cf, Louis Bridges S Jr, Criswell L, Moreland L, Klareskog L, Saevarsdottir S, Padyukov L, Gregersen Pk, Friend S, Plenge R, Stolovitzky G, Oliva B, Guan Y, Mangravite Lm, Bridges Sl, Criswell L, Moreland L, Klareskog L, Saevarsdottir S, Padyukov L, Gregersen Pk, Friend S, Plenge R, Stolovitzky G, Oliva B, Guan Y, Mangravite Lm. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis. Nat Commun. 7:12460 (2016)
  • Gubern A, Joaquin M, Marquès M, Maseres P, Garcia-Garcia J, Amat R, González-Nuñez D, Oliva B, Real Fx, De Nadal E, Posas F. The N-Terminal Phosphorylation of RB by p38 Bypasses Its Inactivation by CDKs and Prevents Proliferation in Cancer Cells. Mol Cell. pii: S1097-2765(16) 30429-4 ( 2016)


For more information about completed and ongoing projects please check:

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