Molecular and cellular neurobiotechnology

Research Topics

Atomic force microscopy / Microarrays analysis / Gene cloning and expression of developmentally regulated genes / Pharmacological treatments to promote axon regeneration / Prion biology / Neurodegenerative diseases / Neural stem cells

During 2010, the research group has developed several studies aimed at understanding some processes of development, neuronal plasticity and neurodegeneration of the central nervous system (CNS). Among them we have demonstrated, in collaboration with other groups, the role of an intracellular adapter Dab1 as a link between different neurodegenerative diseases (Alzheimer’s disease and prion diseases). In addition we have determined the functions of a protein, OMgp, during the development and plasticity of the nervous system. This protein is very active in synaptic transmission and neural plasticity. We have also made progress in understanding the intracellular mechanisms responsible of the failure of axonal regeneration after CNS injury. In this area, we have described that the intracellular kinase GSK3β involved in the inhibitory effects of myelin-associated molecules.


Example of time lapse video using LEICA SP5 spinning disk confocal microscopy showing two olfactory ensheathing glia transiently transfected with Life Act using electroporation procedures. This observation is useful to analyze F-Actin dynamics in living cells under different substrates and only available with high speed confocal capture, and high sensitive camera ORCA 32 bits. Sequential pictures were further analyzed with Metamorph and Matlab software.







In 2010 the group published a methodological review in Nature Protocols on the usefulness of three-dimensional culture in neuropharmacological studies. Moreover, in collaboration with other national groups, we have characterized the process of neurogenesis in the adult hippocampus and its modification by sensory or motor learning.

Finally, group members have collaborated on the study of differential miRNA expression associated with Huntington’s disease.


Example of oligodendrocyte differentiation (green) from human
neuronal stem cells in vitro (HNSC100). In addition to oligodendrocytes,
a feed layer of astrocytes (red) are present in the culture. Cells are
countestained with Hoescht. Picture obtained using an Olympus BX61
microscope equipped with a DP12L high resolution camera and an
incubation chamber LCi, after 15 days in continuous time lapse analysis.

• Prof. Dr. José Antonio del Río | Group Leader
• Dr. Ana Bribian | Postdoctoral Researcher
• Dr. Rosalina Gavín | Postdoctoral Researcher
• Dr. Vanessa Gil | Postdoctoral Researcher
• Dr. Franc Llorens | Postdoctoral Researcher
• Dr. Silvia Vilches | Postdoctoral Researcher
• Patricia Carulla | PhD Student
• Sara Nocentini | PhD Student
• Diego Reginensi | PhD Student
• Oscar Seira | PhD Student
• Cristina Vergara | PhD Student
• Cristina León | Master Student
• Giovanna Tormen | Laboratory Technician

Former Members

• Jorge Gómez | Master Student
  Ed. Hèlix | Baldiri Reixac, 15-21 | 08028 | Barcelona

• Gil, V. & del Río, J. A. (2012). Analysis of axonal growth and cell migration in 3D hydrogel cultures of embryonic mouse CNS tissue. Nature Protocols, 7(2), 268–280.
• Armendariz, B., Bribian, A., Perez-Martinez, E., Martinez, A., de Castro, F., Soriano, E. & Burgaya, F. (2012). Expression of Semaphorin 4F in neurons and brain oligodendrocytes and the regulation of oligodendrocyte precursor migration in the optic nerve. Mol Cell Neurosci., 49(1), 54-67.
• Nocentini, S., Reginensi, D., García, S., Carulla, P., Moreno-Flores, M., Wandosell, F., Trepat, X., Bribian, A. & del Río, J. A. (2011). Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single-cell tracking and traction force microscopy. Cell Mol Life Sci, in press.
• Llorens, F., Gil, V. & del Río, J. A. (2011). Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration. FASEB J, 25(2), 463-75.
• Carulla, P., Bribian, A., Rangel, A., Gavín, R., Ferrer, I., Caelles, C., del Río, J. A. & Llorens, F. (2011). Neuroprotective role of PrPC against Kainate-induced epileptic seizures and cell death depends on the modulation of JNK3 activation by GluR6/7-PSD-95 binding. Mol Biol Cell., in press.
• Llorens, F., Hummel, M., Pastor, X., Ferrer, A., Pluvinet, R., Vivancos, A., Castillo, E., Iraola, S., Mosquera, A., Gonzalez, E., Lozano, J., Ingham, M., Dohm, J., Noguera, M., Kofler, R., del Río, J. A., Bayes, M., Himmelbauer, H. & Sumoy, L. (2011). Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis. BMC Genomics, 12(1), 326.
• Marti, E., Pantano, L., Bañez-Coronel, M., Llorens, F., Miñones-Moyano, M., Porta, S., Sumoy, L., Ferrer, I. & Estivill, X. (2010). A myriad of miRNA variants in control and Huntington’s disease brain regions detected by massively parallel sequencing. Nucl. Acids Res., 38(20), 7219-7235.
• Vitureira, N., Andres, R., Perez-Martinez, E., Martinez, A., Bribian, A., Blasi, J., Chelliah, S., Lopez-Domenech, G., De Castro, F., Burgaya, F., McNagny, K. & Soriano, E. (2010). Podocalyxin is a novel polysialylated neural adhesion protein with multiple roles in neural development and synapse formation. PLoS One, 8(5), e12003.
• Madroñal, A., López-Aracil, C., Rangel, A., del Río, J. A., Delgado-García, J. M. & Gruart, A. (2010). Effects of Enriched Physical and Social Environments on Motor Performance, Associative Learning, and Hippocampal Neurogenesis in Mice. PLoS ONE, 5(6), e11130.
• Messeguer, J., Masip, I., Montolio, M., del Río, J. A., Soriano, E. & Messeguer, A. (2010). Peptoids bearing tertiary amino residues in the n-alkyl side chains: synthesis of a potent inhibitor of Semaphorin 3A. Tetrahedron, 66(13), 2444-2454.
• del Río, J. A. & Soriano, E. (2010). Regenerating cortical connections in a dish: the entorhino-hippocampal organotypic slice co-culture as tool for pharmacological screening of molecules promoting axon regeneration. Nat Protoc, 5(2), 217-26.
• Seira, O., Gavín, R., Gil, V., Llorens, F., Rangel, A., Soriano, E. & del Río, J. A. (2010). Neurites regrowth of cortical neurons by GSK3β inhibition independently of Nogo receptor 1. J Neurochem, 113(6), 1644-58.
• Gil, V., Bichler, Z., Lee, J. K., Seira, O., Llorens, F., Bribian, A., Morales, R., Claverol-Tinturé, E., Soriano, E., Sumoy, L., Zheng, B. & del Río, J. A. (2010). Developmental Expression of the Oligodendrocyte Myelin Glycoprotein in the Mouse Telencephalon. Cerebral Cortex, 20(8), 1769-1779.
• Montolio, M., Messeguer, J., Masip, I., Guijarro, P., Gavín, R., del Río, J. A., Messeguer, A. & Soriano, E. (2009). A semaphorin 3A inhibitor blocks axonal chemorepulsion and enhances axon regeneration. Chemistry & Biology, 16(7), 691-701.
• Rangel, A., Madroñal, N., Massó, ., Gavín, R. & Llorens, F. (2009). Regulation of GABAA and Glutamate Receptor Expression, Synaptic Facilitation and Long-Term Potentiation in the Hippocampus of Prion Mutant Mice. PLoS ONE, 4(10), e7592.
• Nicolas, O., Gavín, R. & del Río, J. A. (2009). New insights into cellular prion protein (PrPc) functions: the "ying and yang" of a relevant protein. Brain Research Reviews, 61(2), 170-184.
• Aguado, F., Diaz-Ruiz, C., Parlato, R., Martinez, A., Carmona, M. A., Bleckmann, S., Urena, J. M., Burgaya, F., del Río, J. A., Schutz, G. & Soriano, E. (2009). The CREB/CREM Transcription Factors Negatively Regulate Early Synaptogenesis and Spontaneous Network Activity. J. Neurosci., 29(2), 328-333.
• Gavín, R., Ferrer, I. & del Río, J. A. (2009). Involvement of Dab1 in APP processing and B-amyloid deposition in sporadic Creutzfeldt-Jakob patients. Neurobiology of Disease, 37(2), 324-329.
• Morales, R., Riss, M., Wang, L., Gavín, R., del Río, J. A., Alcubilla, R. & Claverol-Tinturé, E. (2008). Integrating multi-unit electrophysiology and plastic culture dishes for network neuroscience. Lab Chip, 8, 1896-1905.
• Llorens, F., Gil, V., Iraola, S., Carim-Todd, L., Martí, E., Estivill, X., Soriano, E., del Río, J. A. & Sumoy, L. (2008). Developmental analysis of Lingo-1/Lern1 protein expression in the mouse brain: Interaction of its intracellular domain with Myt1l. Developmental Neurobiology, 68(4), 521-541.
• Gavín, R., Ureña, J., Rangel, A., Pastrana, M. A., Requena, J. R., Soriano, E., Aguzzi, A. & del Río, J. A. (2008). Fibrillar prion peptide PrP(106-126) treatment induces Dab1 phosphorylation and impairs APP processing and A[beta] production in cortical neurons. Neurobiology of Disease, 30(2), 243 - 254.
• Bribian, A., Esteban, P. F., Clemente, D., Soussi-Yanicostas, N., Thomas, J.-L., Zalc, B. & de Castro, F. (2008). A novel role for anosmin-1 in the adhesion and migration of oligodendrocyte precursors. Developmental Neurobiology, 68(13), 1503-1516.
• Meur, A. M., Zheng, B., Soriano, E. & del Río, J. A. (2007). Involvement of the Myelin-Associated Inhibitor Nogo-A in Early Cortical Development and Neuronal Maturation. Cerebral Cortex, 17(10), 2375-2386.
• del Río, J. A. & Soriano, E. (2007). Overcoming Chondroitin Sulphate Proteoglycan Inhibition of Axon Growth in the Injured Brain: Lessons from Chondroitinase ABC. Current Pharmaceutical Design, 13, 2485-2492(8).
• Nicolas, O., Gavín, R., Braun, N., Ureña, J. M., Fontana, X., Soriano, E., Aguzzi, A. & del Río, J. A. (2007). Bcl-2 overexpression delays caspase-3 activation and rescues cerebellar degeneration in prion-deficient mice that overexpress amino-terminally truncated prion. The FASEB Journal, 21(12), 3107-3117.
• Merchán, P., Bribian, A., Sánchez-Camacho, C., Lezameta, M., Bovolenta, P. & de Castro, F. (2007). Sonic hedgehog promotes the migration and proliferation of optic nerve oligodendrocyte precursors. Molecular and Cellular Neuroscience, 36(3), 355 - 368.
• Soriano, E. & del Río, J. A. (2005). The cells of Cajal-Retzius: Still a mystery one century later. Neuron, 46(3), 389-394.

Projects

• BESAD-P Biomarkers of early stages of Alzheimer disease-prevention (CIBERNED intramural project) (2010-2012) José Antonio Del Río
• PRIORITY Protecting the food chain of prions: Shaping European priorities through basic and applied research (FP7 EU program) (2010) José Antonio Del Río
• Funciones de nuevos genes candidatos y proteínas asociadas a mielina durante el desarrollo y regeneración de las conexiones corticales (MEC) José Antonio Del Río
• CIBERNED Spanish Network of Neurodegenerative Diseases of the Ministry of Heath (FISS) (2009) Prof. Dr. José Antonio Del Río
• Differentiation of GABAergic interneuron subtypes in the mouse cerebral cortex (GABA cell types) (2008-2011) José Antonio Del Río
• DEVREG Caracterización funcional de genes regulados durante la ontogenia del SNC en el desarrollo cortical y la regeneración axonal (2009-2012) José Antonio Del Río
• Enfermedades neurodegenerativas (2008-2012) José Antonio Del Río

Collaborations

• Dr. Jung Keun Hyun Dankook University, Yongin (Korea)


• Prof. Javier de Felipe Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid (Spain)


• Dr. Fernando de Castro Hospital Nacional de Parapléjicos, Toledo (Spain)


• Dr. Adolfo Lopéz de Munain Hospital de Donostia, San Sebastian (Spain)


• Prof. Jose Manuel García Verdugo Facultad de Ciencias, Universidad de Valencia (Spain)


• Prof. Fernando Albericio Institute for Research in Biomedicine (IRB), Barcelona, Spain


• Prof. Ernest Giralt Institute for Research in Biomedicine (IRB), Barcelona, Spain


• Dra. Miriam Royo Institute for Research in Biomedicine (IRB), Barcelona, Spain


• Prof. Josep A. Planell Institut de Bioenginyeria de Catalunya (IBEC)


• Prof. Josep Samitier Institut de Bioenginyeria de Catalunya (IBEC)


• Prof. Jesús Ávila Consejo Superior de Investigaciones Científicas (CSIC). Universidad Autónoma de Madrid


• Prof. Isidro Ferrer Institut d'Investigació Biomèdica de Bellvitge (IDIBELL). Universitat de Barcelona


• Prof. Binhai Zheng Dept. Neuroscience, University of California at San Diego, La Joya, California


• Prof. Marc Tessier Lavigne Genentech, Inc., South San Francisco, California, USA


• Prof. Manuel Nieto Sampedro

  Instituto Cajal, Madrid.

• Neural stem cell culture
• Microscopy facility (Olympus BX61 and Olympus IX71 with LCi culture system)
• Electroporation system (BTX 600)
• Pressure microinjection system
• Protein expression and purification systems
• Technology of neuronal culture facilities (2D and 3D)
• Lentiviral production and characterization
• Gradient thermocycler (PCR)
• Protein and DNA electrophoresis
• In situ hybridization oven

02/01/2012

Shedding light on misbehaving cells

Much like a kindergarten full of unruly toddlers, the cells that contribute to the body’s crucial processes can’t always be trusted to do what you want or expect them to do. Now IBEC researchers have made an important breakthrough that could contribute to the development of therapies for spinal and neural diseases: they’ve figured out exactly what it is that makes certain cells misbehave in particular circumstances.

 

26/07/2011

'Identifying an essential interaction for epilepsy'

The Molecular and Cellular Neurotechnology group's recent paper on the development of epilepsy made the news today in Diario Medico, Spain’s leading newspaper for health professionals.

 

16/01/2011

'Beating the regeneration blockers' on the web

The 12 November press release about the Molecular and Cellular Neurobiotechnology group's research on inhibitory molecules in neuroregeneration, 'Beating the regeneration blockers', was picked up by various online scientific and health news sites including www.sciencedaily.com, the UK's MS Trust and Cell DNA.

 

12/11/2010

Beating the regeneration blockers

IBEC researchers shed light on inhibitory molecules in neuroregeneration

 

23/11/2009

Advances in neuronal regeneration

Prof. José Antonio del Río, leader of the Molecular and Cellular Neurobiotechnology research line at IBEC, has participated in a study on neural regeneration published in the journal Chemistry and Biology of the Cell group.