Documente Academic
Documente Profesional
Documente Cultură
24/6/15 12:53
05
Biologa Celular
y Molecular
Cellular & Molecular Biology
102
104
Germn Rivas Caballero Carlos Alfonso Botello, Mercedes Jimnez Sarmiento y Silvia Zorrilla Lpez
Bioqumica de Sistemas de la Divisin Bacteriana | Systems Biochemistry of Bacterial Division
106
Rafael Giraldo Surez M. Elena Fernndez-Tresguerres Rodrguez-Vigil y Juan Francisco Gimnez Abin
Ensamblajes Macromoleculares Microbianos Sintticos | Synthetic Microbial Macromolecular Assemblies
108
Jorge Bernardo Schvartzman Blinder Dora Beatriz Krimer Smunis y Pablo Hernndez Valenzuela
Biologa Molecular de los Cromosomas | Molecular Biology of the Chromosomes
110
112
Patricia Boya
Funciones de la Autofagia en la Fisiopatologa de los Organismos | Roles of Autophagy in Health and Disease
114
116
118
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Profesor de Investigacin
penalva@cib.csic.es
Cientfico Titular
eespeso@cib.csic.es
PhD, 1982
Universidad Autnoma de Madrid
Postdoctoral
Antibiticos SA (Madrid)
Institut de Genetique et Microbiologie,
Universidad de Paris (Orsay, Paris)
Cientfico Titular, 1987
Jefe de Grupo, 1987
Profesor de Investigacin, 2001
CIB, CSIC
Visiting Scientist, 2005-2006
MRC Laboratory of Molecular Biology
(Cambridge, UK)
Elegido miembro, 2000
EMBO
PhD, 1989
Universidad Complutense de Madrid
Postdoctoral, 1997-1999
Imperial College London
EMBO-Postdoctoral Fellow
Contratado, 2001-2004
Ramn y Cajal
Cientfico Titular, 2004
Jefe de Grupo, 2004
CIB, CSIC
Secretario, 2004-2008
Grupo Especializado de Hongos Filamentosos
y Levaduras (SEM)
Maria-Tsampika Manoli
Miguel Hernndez Gonzlez
http://www.cib.csic.es/es/grupo.php?idgrupo=8
Figura 1 | Figure 1
Portada del nmero de Julio de la revista Autophagy, por el artculo de Pinar et al.
que demuestra que las membranas de la ruta de autofagia en hongos derivan de
estructuras asociadas con el ER que se asemejan a los omegasomas de metazoos.
Cover of the July 2013 issue of the journal Autophagy, for the article by Pinar et al. showing
that fungal autophagic membranes derive from ER-associated srtuctures resembling
metazoan omegasomes.
Financiacin | Funding
BIO2012-30695 (MINECO)
RD12/0018/0007 (ISCIII-FEDER)
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Aspergillus Molecular
and Cellular Biology
Aspergillus nidulans is a genetic model well suited
for studying polarised exocytosis and long-distance
transport mediated by actin and microtubules.
Intracellular traffic resembles that of metazoan cells,
yet the organism is haploid, genetically amenable
and microscopy-friendly.
Publicaciones Seleccionadas
Selected Publications
Pinar, M, A Pantazopoulou & MA Pealva [2013] Live-cell imaging of Aspergillus
nidulans autophagy: RAB1 dependence, Golgi independence and ER involvement.
Autophagy 9: 1-20. (Journal Cover).
Pinar, M, Pantazopoulou, A, Arst, HN, Jr, and Pealva, MA [2013] Acute inactivation
of the Aspergillus nidulans Golgi membrane fusion machinery: correlation
of apical extension arrest and tip swelling with cisternal disorganization. Mol.
Microbiol. 89: 228-248. (Editorial Minireview).
Figura 2 | Figure 2
Sealizacin del factor CrzA y anlisis fenotpico de cepas nulas CrzA y SltA. A) CrzA
muestra diferentes estados de fosforilacin y la adicin de calcio o la alcalinizacin del
medio altera el patrn de fosforilacin. RC=resting cells. B) La ausencia de CrzA causa
sensibilidad al calcio mientras que una cepa nula sltA es sensible a una gran variedad
de cationes, y ambas a pH alcalino.
Signalling of CrzA factor and phenotypic analyses of null crzA and sltA strains. A) CrzA
displays different phosphorylation states. Addition of calcium or medium alkalinisation
alter the phospho-pattern. RC=resting cells. B) Absence of CrzA activity results in calcium
sensitivity. A null sltA strain is sensitive to a large variety of cations, both null strains are
sensitive to alkalinity.
Zhang, J, R Qiu, HN Arst, Jr, MA Penalva, and X Xiang [2014] HookA is a novel
dynein-early endosome linker critical for cargo movement in vivo. Journal of Cell
Biology 204:1009-1026. (Editorial comment as Journal Focus).
Pealva MA, Lucena-Agell D, Arst HN Jr. [2014] Liaison alcaline: Pals entice
non-endosomal ESCRTs to the plasma membrane for pH signaling. Curr Opin
Microbiol. 22C:49-59.
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Investigador, 1994
Cientfico Titular, 1995
Jefe de Grupo,1996
Investigador Cientfico, 2006
CIB, CSIC
http://www.cib.csic.es/es/grupo.grivas
Bioqumica de Sistemas de
la Divisin Bacteriana
Nuestro objetivo es entender cmo los elementos de la maquinaria de la
divisin bacteriana (el divisoma) funcionan como un sistema integrado de
interacciones moleculares para ejercer su funcin esencial. Desarrollamos
y aplicamos novedosos abordajes de reconstitucin bioqumica para
construir, con un conjunto mnimo de protenas, ensamblajes funcionales
de divisin en ausencia de clulas.
Financiacin | Funding
HEALTH-F3-2009-223432. (Comunidad Europea)
RGP0050-2010. (Human Frontier Science
Program)
BIO2011-28941-C03. (MINECO)
Publicaciones
Seleccionadas
Selected Publications
Ahijado-Guzmn R, Alfonso C, Reija B, Salvarelli E,
Mingorance J, Zorrilla S, Monterroso B, Rivas G [2013]
Control by potassium of the size-distribution of
Escherichia coli FtsZ polymers is independent of
GTPase activity. J. Biol. Chem. 288:27358-27365.
Cabr EJ, Snchez-Gorostiaga A, Carrara P, Ropero
N, Casanova M, Palacios P, Stano P, Jimnez M,
Rivas G, Vicente M [2013] Bacterial division proteins
FtsZ and ZipA induce vesicle shrinkage and cell
membrane invagination. J. Biol. Chem. 288:2662526634.
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Figura 1 | Figure 1
Reconstitucin de elementos del protoanillo en vesculas. Mtodo de emulsin (A)
para encapsular y polimerizar FtsZ dentro de GUVs permeables (B). (C) Contraccin
de GUVs debido a la interaccin de polmeros de FtsZ y ZipA asociada a la membrana
(0, 5, 10 min). (D) Bloqueo de la contraccin al aadir un pptido de FtsZ que inhibe la
interaccin FtsZ-ZipA (Cabr et al. 2013; Rivas et al. 2014).
Reconstitution of proto-ring elements in vesicles. Water-in-oil droplet transfer method (A)
used to encapsulate and polymerize FtsZ inside permeable GUVs (B). (C) Shrinking of GUVs
through the interaction of FtsZ with membrane-associated ZipA (0, 5 and 10). (D) Blocking
shrinkage by the addition of an FtsZ-derived peptide that inhibits FtsZ-ZipA interaction.
(Cabr et al. 2013; Rivas et al. 2014).
Figura 2 | Figure 2
Anlisis biofsico de los diferentes comportamientos de los oligmeros de GDPFtsZ (gris) y los polmeros de GTP-FtsZ (negro) a partir de medidas de velocidad de
sedimentacin (A), dependencia con la concentracin de la dispersin de luz esttica
(B), dispersin de luz dinmica (C) y espectroscopa de correlacin de fluorescencia
(D). (Monterroso et al. 2013).
Biophysical analysis of the different behavior of GDP-FtsZ oligomers (grey) and GTPFtsZ polymers (black) from measurements of sedimentation velocity (A), concentration
dependence static light scattering (B), dynamic light scattering (C) and fluorescence
correlation spectroscopy (D). (Monterroso et al. 2013).
Systems Biochemistry
of Bacterial Division
Our research aims at understanding how the elements of the bacterial division machinery (the divisome) work
together as an integrated system of molecular interactions to fulfill its essential function. To address these
questions we develop and apply novel biochemical reconstitution approaches to build, with a minimum set of
elements, functional division assemblies in the absence of cells.
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Postdoctoral, 1992-1994
Divisin de Estudios Estructurales,
Laboratorio de Biologa Molecular del MRC
(Cambridge, UK)
http://www.cib.csic.es/es/grupo.php?idgrupo=61
Ensamblajes Macromoleculares
Microbianos Sintticos
Mediante aproximaciones de Biologa Sinttica, desarrollamos mdulos derivados de RepA, una protena de
replicacin propia de plsmidos bacterianos, que permiten controlar el ensamblaje amiloide en condiciones
cuasifisiolgicas y construir en microorganismos una proteinopata amiloide modelo genrica. Esperamos
as poder deconstruir e intervenir las rutas y mecanismos de citotoxicidad compartidos entre las amiloidosis
bacterianas y humanas.
Patentes | Patents
Rafael Giraldo y Mara Moreno del lamo. 25 septiembre 2013. Anticuerpo
monoclonal B3h7 anti-oligmeros amiloides RepA-WH1, hibridoma que lo
produce y aplicaciones. OEPM / P201331391
Financiacin | Funding
CSD2009-00088 (MINECO)
BIO2012-30852 (MINECO)
Publicaciones Seleccionadas
Selected Publications
Lane AB, Gimnez-Abin JF, Clarke DJ [2013] A novel chromatin tether domain
controls topoisomerase IIa dynamics and mitotic chromosome formation. J Cell
Biol 203:471-486.
Gasset-Rosa F, Coquel AS, Moreno-del lamo M, Chen P, Song X, Serrano AM,
Fernndez-Tresguerres ME, Moreno-Daz de la Espina S, Lindner AB, Giraldo R
[2014] Direct assessment in bacteria of prionoid propagation and phenotype
selection by Hsp70 chaperone. Mol Microbiol 91:1070-1087.
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By means of Synthetic Biology approaches, we are developing modules derived from RepA, a DNA replication
protein in bacterial plasmids, which allow control on amyloid assembly under quasi-physiological conditions and the
construction in microorganisms of a generic amyloid proteinopathy. We thus aim later to deconstruct, and enable
intervention on, the pathways and mechanisms of cytotoxicity shared by human and bacterial amyloidosis.
Figura 1 | Figure 1
La amiloidognesis de RepA-WH1 in vitro (dcha.) implica la disociacin, mediada por efector (DNA), de dmeros en monmeros metaestables que se ensamblan jerrquicamente en
filamentos y fibras amiloides entrelazados. Estructuras resueltas en colaboracin con A. Romero (2003) y O. Llorca (2015). En E. coli los agregados amiloides (izda., sectores rojos) son
citotxicos y verticalmente transmisibles.
RepA-WH1 amyloidogenesis in vitro (right) implies effector (DNA)-mediated dissociation of dimers into metastable monomers that assemble hierarchically into intertwined amyloid filaments and variably
twisted fibres. Structures solved in collaboration with the groups of A. Romero (2003) and O. Llorca (2015). In E. coli, amyloid aggregates (left, red sectors) are cytotoxic and vertically inheritable.
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Postdoctoral, 1980-1982
Brookhaven National Laboratory (New York,
USA)
Fullbright Fellow, 1987-1989
Albert Einstein College of Medicine
(New York, USA)
Cientfico Titular, 1985
Jefe de Grupo, 1980
Investigador Cientfico, 2002
Profesor de Investigacin, 2007
CIB, CSIC
Celia Bolomburu
Idoia Garca Hernando
Leticia Garca Martnez
Mara-Luisa Martnez-Robles
http://www.cib.csic.es/es/grupo.php?idgrupo=2
Publicaciones Seleccionadas
Selected Publications
Schvartzman JB, Martnez-Robles ML, Hernndez P, Krimer DB [2013] The benefit
of DNA supercoiling during replication. Biochemical Society Transactions 41:
646-651.
Schvartzman JB, Martnez-Robles ML, Hernndez P, Krimer DB [2013] Plasmid DNA
topology assayed by two-dimensional agarose gel electrophoresis. In Methods
Mol Biol 1054: 121-132, DNA Electrophoresis: Methods and Protocols (Svetlana
Makovets, ed.) Springer Science Business Media, New York.
Fernndez-Nestosa MJ, Monturus ME, Snchez Z, Torres F, Fernndez A, Fraga
M, Hernndez P, Schvartzman JB, Krimer DB [2013] DNA methylation-mediated
silencing of PU.1 in leukemia cells resistant to cell differentiation. SpringerPlus 2,
392 DOI:10.1186/2193-1801-2-392.
Figura 2 | Figure 2
Molculas de DNA aisladas de clulas MEL DS19 durante la diferenciacin extendidas
por peinado molecular. La deteccin inmunocitoqumica de tramos marcados
secuencialmente con IdU (en rojo) seguido de CldU (en verde) permite identificar los
sitios de iniciacin de la replicacin y la distancia entre orgenes as como calcular la
velocidad de progreso de las horquillas.
Selected DNA molecules isolated from MEL DS19 cells along differentiation stretched by
DNA combing. The immunocytological detection of sequentially labelled tracks with IdU
(red) followed by CldU (green) allows the identification of replication origins and inter-origin
distances as well as the calculation of the rate of replication fork progression.
Cebrin J, Castn A, Martnez V, Parra C, Kadomatsu-Hermosa MJ, FernndezNestosa MJ, Schaerer C, Hernndez P, Krimer DB, Schvartzman JB [2015] Direct
evidence for the formation of precatenanes during DNA replication. Journal of
Biol Chem DOI: 10.1074/jbc.M115.642272.
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We are interested in the relationships and coordination between biological processes where DNA is involved:
replication, transcription, repair and recombination, how are they regulated and how they alter or are affected
by genetic, epigenetic and environmental factors such as DNA topology, chromatin organization and nutritional
stress.
Financiacin | Funding
BFU2011-22489 (MINECO)
Figura 1 | Figure 1
Anlisis de la topologa del DNA. A) La electroforesis bidimensional en geles de agarosa con distintas concentraciones de cloroquina permite distinguir todos los topoismeros de
molculas circulares covalentemente cerradas (CCCs). As se puede identificar el topoismero ms abundante y calcular la densidad de superenrollamiento. B) El recubrimiento del
DNA con la protena RecA permite visualizar molculas encadenadas por microscopa electrnica.
Analysis of DNA topology. A) Two-dimensional (2D) agars gel electrophoresis in the presence of different concentrations of chloroquine allows the identification of all the topoisomers of covalentlyclosed circles (CCCs). This technique can be used to recognize the most abundant topoisomer to calculate supercoiling density. B) Covering DNA molecules with the bacterial protein RecA allows
the identification of catenanes by electron microscopy.
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Postdoctoral, 1985-1989
National Institute for Medical Research
(MRC, UK)
Cientfico Titular, 1991
Jefe de Grupo, 1991
Investigador Cientfico, 2008
CIB, CSIC
https://www.cib.csic.es/es/grupo.php?idgrupo=14
El Sistema Polycomb
de Regulacin
Epigentica
El grupo de genes Polycomb (PcG) codifica
reguladores epigenticos que forman complejos con
actividad modificadora de cromatina. Bien conocidos
como reguladores transcripcionales durante el
desarrollo embrionario, participan crticamente en
diferenciacin y homeostasis celulares, actuando
sobre progenitores. Nuestro trabajo se centra en los
complejos que monoubiquitinan la histona H2A.
Figura 1 | Figure 1
Asociacin de RING1B con la maquinaria de replicacin. Sitios de interaccin de
RING1B con la abrazadera de replicacin PCNA, detectada en un ensayo de ligacin
en proximidad (PLA) como focos coloreados en rojo. DNA nuclear (teido con DAPI,
A) y replicando (marcado mediante incorporacin de EdU, un anlogo de timidina, en
verde, B). Barra, 10 m.
Asociation of RING1B with the replication machinery. Proximity ligation assay (PLA) detects
RING1B association to the replicative slide clamp PCNA, visualized as red foci. Total DNA
(DAPI, A) and replicating DNA (B, EdU). Scale bar, 10 m.
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The Polycomb group (PcG) of genes encode epigenetic regulators assembled in complexes displaying
chromatin modifying activities. Well known developmental regulators, they participate in cell differentiation
and tissue homeostasis with an emphasis in progenitor cells. We focus on core subunits of complexes that
monoubiquitylate histone H2A.
Financiacin | Funding
BFU2010-18146 (MINECO)
SAF2013-47997-P (MINECO)
Publicaciones Seleccionadas
Selected Publications
Morimoto-Suzki N, Hirabayashi Y, Tyssowski K, Shinga J,Vidal M, Koseki H, Gotoh
Y [2014] The polycomb component Ring1B regulates the timed termination
of subcerebral projection neuron production during neocortical development.
Development 141:4343-53.
Vidal M [2014] Polycomb complexes: chromatin regulators required for cell diversity
and tissue homeostasis. pp95-139. C. Bonifer and P.N. Cockerill (eds.).
Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell
Development, Epigenetics and Human Health, Springer-Verlag Berlin Heidelberg.
Kondo T, Isono K, Kondo K, Endo TA, Itohara S, Vidal M, Koseki H [2014] Polycomb
potentiates Meis2 activation in midbrain by mediating interaction of the promoter
with a tissue-specific enhancer. Dev Cell 28:94-101.
Figura 2 | Figure 2
Mitosis aberrante en clulas mutantes que carecen de RING1A y RING1B. La tincin
de DNA con DAPI muestra un puente cromosomal probablemente consecuencia de
replicacin incompleta. Barra, 10 m.
Aberrant mitosis of RING1A and RING1B-deficient cells. DAPI-stained mitosis showing
chromosomal bridges indicating incomplete DNA replication. Scale bar, 10 m.
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Patricia Boya
Cientifica titular
pboya@cib.csic.es
PhD, 2000
Universidad de Navarra
Postdoctoral, 2001-2005
CNRS (Pars, Francia)
Universisty of Cambridge (UK)
Contrato, 2005-2009
Ramn y Cajal
http://www.cib.csic.es/es/grupo.php?idgrupo=73
Funciones de la Autofagia en la
Fisiopatologa de los Organismos
En nuestro laboratorio utilizamos modelos celulares y animales para comprender el papel de la autofagia en
la fisiologa y la patologa de los organismos. Este es un proceso de degradacin intracelular que permite la
eliminacin y el reciclaje de componentes celulares. Es una importante respuesta frente al ayuno nutricional,
participa en la degradacin de orgnulos celulares y permite la supervivencia en situaciones de estrs.
Figura 1 | Figure 1
Distribucin de la poblacin total del clulas ganglionares de la retina de ratn
montada en plano y teidas para el factor de transcripcin Brn3a (A y B), y
representacin del mapa de isodensidades de nmero de clulas ganglionares (C y D).
Retinal ganglion cell distribution in mouse retinal flatmounts stained for the transcription factor
Brna (A and B). Isodensity map of retinal ganglion cell numbers (C and D).
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Publicaciones Seleccionadas
Selected Publications
Esteban-Martnez L, Boya P. [2015] Autophagic flux determination in vivo
and ex vivo. Methods. Jan 30. pii: S1046-2023(15)00014-6. doi: 10.1016/j.
ymeth.2015.01.008.
Rodrguez-Muela N, Hernndez-Pinto AM, Serrano-Puebla A, Garca-Ledo L, Latorre
SH, de la Rosa EJ, Boya P [2014] Lysosomal membrane permeabilization and
autophagy blockade contribute to photoreceptor cell death in a mouse model of
retinitis pigmentosa. Cell Death Differ. 2014 Dec 12. doi: 10.1038/cdd.2014.203.
Wang F, Bexiga MG, Anguissola S, Boya P, Simpson JC, Salvati A, Dawson KA.
[2013] Time resolved study of cell death mechanisms induced by amine-modified
polystyrene nanoparticles. Nanoscale. 2013 Nov 21;5(22):10868-76. doi: 10.1039/
c3nr03249c.
Boya P, Codogno P. [2013] Cell biology: Recycling in sight. Nature. 2013 Sep
5;501(7465):40-2. doi: 10.1038/501040.
Boya P, Reggiori F, Codogno P. [2013] Emerging regulation and functions of
autophagy. Nat Cell Biol. 2013 Jul;15(7):713-20. doi: 10.1038/ncb2788.
Oeste CL, Seco E, Patton WF, Boya P, Prez-Sala D [2012] Histochem Cell Biol.
2013 May;139(5):659-70. doi: 10.1007/s00418-012-1057-6.
Rodrguez-Muela N, Koga H, Garca-Ledo L, de la Villa P, de la Rosa EJ, Cuervo
AM, Boya P. [2013] Balance between autophagic pathways preserves retinal
homeostasis. Aging Cell. 2013 Jun;12(3):478-88. doi: 10.1111/acel.12072.
Roles of
Autophagy
in Health
and Disease
Financiacin | Funding
i-link0701 (CSIC 2014-2015)
Provital 2013-2016
Figura 2 | Figure 2
Corte de una retina de ratn que
expresa constitutivamente el
marcador de autofagosomas LC3
unido a la protena fluorescente GFP
(tincin en verde). En rojo se han
marcado las mitocondrias que se han
teido utilizando el anticupero para la
protena mitocondrial TOMM20, y en
azul se observan los ncleos teidos
con el marcador para DNA DAPI.
Section of a retina from the
GFP-LC3 mouse, an animal model
that constitutively expresses the
autophagosomal marker LC3 coupled
to the fluorescent protein GFP in green.
Mitochondria stained with TOMM20 are
labelled in red and nuclei are revealed
with the DNA marker DAPI in blue.
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http://www.cib.csic.es/es/grupo.php?idgrupo=18
Biologa
Molecular de la
Gametognesis
Nuestro inters se ha centrado en los ltimos aos
en la biognesis y funcin de diferentes RNAs
reguladores, no-codificantes, de pequeo tamao
(tales como miRNAs, piRNAs , endo-siRNAs,
snoRNAs) en el desarrollo y la diferenciacin de la
lnea germinal y la reproduccin en mamferos y su
papel en la desregulacin gentica y epigentica
mediada por algunos reprotxicos ambientales.
Figura 1 | Figure 1
Apoptosis en clulas germinales primordiales (PGCs) de ratones machos expuestos
durante su vida fetal a vinclozolina (un fungicida utilizado en la agricultura, con efectos
antiandrognicos). Co-deteccin en microscopa confocal de apoptosis por TUNEL y
marcaje especfico con SSEA-1 para clulas PGC (13,5 das postcoitum). En la parte
superior de la figura: Testis junto con el MesoNefros.
Apoptosis in primordial germ cells (PGCs) of male mice exposed during fetal life to vinclozolin
(a widely used fungicide in agriculture, with antiandrogenic effects). Examples of co-detection
by confocal microscopy analysis of apoptosis by TUNEL and SSEA-1 positive PGCs cells
(from 13.5 days post coitum embryos). Testis showed at the top of the figure along with the
MesoNephros.
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he small non-coding RNAs (sncRNAs) are considered as postranscriptional key regulators of germ cell development. In addition to microRNAs (miRNAs) endo-siRNAs and PIWI-interacting
RNAs (piRNAs), other sncRNAs generated from small nucleolar RNAs
(snoRNAs), -tRNAs or rRNAs-derevatives may also play important regulatory roles in gametogenesis and fertilization. Combining next generation sequencing (NGS), bioinformatics and cell and molecular biology
approaches we are characterizing the regulatory landscape of small
non-coding RNAs during germ cell dierentiation from primordial germ
cells (PGCs) to gameta and the consequences of the expression of the
dierent classes of these small RNAS in fertilization and early preimplantation development. Both, microRNAs and snoRNA-derived small RNAs
are abundantly expressed in PGCs but transiently replaced by piRNAs
in spermatozoa and endo-siRNAs in oocytes and zygotes. Interestingly,
miRNA sequence variants also shows an increment of non-canonical
microRNA forms along male germ cell dierentiation.
Publicaciones Seleccionadas
Selected Publications
Garca-Lpez J., Alonso L., Crdenas D.B., Artaza-Alvarez H, Hourcade J.de D.,
Martinez S., Brieo-Enrquez M. A., and del Mazo J. [2015] Diversity and functional
convergence of small non-coding RNAs in male germ cell differentiation and
fertilization. RNA, 21: 946-962.
Garca-Lpez J., Hourcade JdD, Alonso L., Crdenas D.B. and del Mazo J. [2014]
Global characterization and target identification of piRNAs and endo-siRNAs in
mouse gametes and zygotes. BBA-Gene Regulatory Mechanisms. 1839:463475.
G. M. Oresti,. J. Garca-Lpez, M. I. Aveldao and J. del Mazo [2013] Cell-typespecific regulation of genes involved in testicular lipid metabolism: fatty acidbinding proteins, diacylglycerol acyltransferases and perilipin. Reproduction
146, 471-480.
J. Garca-Lpez, M.A. Brieo-Enrquez and J. del Mazo [2013] MicroRNA
biogenesis and variability. BioMolecular Concepts. 4(4): 367380.
Molecular Biology
of Gametogenesis
Other functional alternatives in the miRNAs such as RNA editing mechanisms are also being analysed in our system. Adenosine-to Inosine
(A-to-I) editing represents a post-transcriptional modication of doublestranded RNA, including miRNA precursors. Inosine is recognized as
guanosine (G) by the cell machinery, which aects the subsequent
processing of edited molecules. We discovered that both active editing
and the degradation of edited precursor RNA molecules occur during the
perifertilization period.
We are also applying these basic gene regulatory aspects to the eect of
reprotoxicants. Multiple studies demonstrated the association between
exposure to environmental toxicants -such as the so-called endocrine
disruptors- and developmental dysfunctions in germ cells. We are studying how prenatal exposure to this compounds could induce induces epigenetic changes in the expression of miRNAs in PGCs in the following
non-exposed generations, even at low level of exposure.
Figura 2 | Figure 2
Financiacin | Funding
11-MRES-PNRPE-9-CVS-072-N210064934 (Ministre de lEcologie,
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Postdoctoral, 1991-1993
University of California Berkeley (USA)
http://www.cib.csic.es/grupo.php?idgrupo=67
Reconocimiento Clula-Biomaterial
Se investiga la respuesta celular y molecular de la clula al interaccionar con materiales metlicos y cermicos de
aplicacin en reparacin sea. Entre los metlicos se analizan aleaciones de Cobalto-Cromo y de biodegradables
de base Magnesio y, entre los cermicos, las hidroxiapatitas. Se estudian los efectos de las partculas metlicas del
desgaste-corrosin del material implantado. En cermicos, se disean superficies con distintas protenas.
Figura 1 | Figure 1
Microscopa multidimensional en tiempo real in vivo de macrfagos J774 en presencia de partculas de magnesio. Imgenes del cultivo de macrfagos expuesto a las partculas de
Mg (1 mg/ml; negro) durante distintos tiempos (0 y 24 horas). A las 24 horas, los macrfagos se dividen y algunos mueren al interaccionar con las partculas que se van degradando
durante el cultivo. (Referencia Alvarez F. y colab. en Microscopy: advances in scientific research and education).
In vivo time-lapse multidimensional microscopy of macrophages J774 in presence of magnesium particles. Images of macrophages culture exposed to Mg particles (1 mg/ml; black images) at
different times (0 and 24 hours). At 24 h., some macrophages duplicate and those located close to particles displayed morphological changes that developed in cell death. Mg particles degrade and
become clear. (Reference Alvarez F. et al. in Microscopy: advances in scientifc research and education).
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Research is focus in the analysis of the molecular and cell response upon interaction with metallic and ceramic
materials for application in bone tissue repair. Metallic materials as cobalt-chromium alloys with high carbon
content and some biodegradable magnesium-base, and ceramics as hydroxyapatites are selected. The effect on the
cell of metallic debris, particles and ions, are under study. In ceramics, new surfaces are designed with proteins.
Cell-Biomaterial Recognition
New ceramic materials hydroxyapatite-based are under study upon functionalization with proteins, as are several growth factors that promotes
tissue vascularization and increase the biological activity of other peptides
involved in bone tissue growth.
Publicaciones Seleccionadas
Selected Publications
Lozano RM*, Prez-Maceda BT, Carboneras M, Onofre-Bustamante E, GarcaAlonso MC, Escudero ML [2013] Response of MC3T3-E1 osteoblasts, L929
fibroblasts and J774 macrophages to fluoride surface-modified AZ31 magnesium
alloy. Journal of Biomedical Materials Research: Part A. 101: 2753-2762.
*Corresponding author.
Alvarez F, Lozano Puerto R, Prez-Maceda B, Grillo C, Schilardi P, Fernndez
Lorenzo M [2013] Efecto de micropartculas de Mg con y sin tratamiento con
KF en clulas osteoblsticas y macrofagos. The Journal of the Argentine
Chemical Society. 100: 48-52.
Billi F, Iglesias C, Onofre E, Lozano RM, Prez-Maceda B, Rubio JC, Escudero ML,
Garca-Alonso MC [2013] Characterization of oxidized TiAlV after fretting-corrosion
tests using near-field microscopy. British Journal of Surgery. Abstract. 100
(Suppl. 1): 13.
Alvarez F, Lozano Puerto RM, Prez-Maceda BT, Grillo CA, Fernndez Lorenzo MA
[2014] Multidimensional microscopy: A suitable technique to follow in vivo the
interaction between biodegradable biomaterials and cells. In Microscopy:
advances in scientific research and education Microscopy book n
6 Vol.1. Editor: A. Mndez-Vilas. Editorial: Formatex Research Center (Badajoz,
Espaa): 523-529.
Financiacin | Funding
MAT2011-29152-C02-02 (MINECO)
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http://www.cib.csic.es/es/grupo.php?idgrupo=31
Figura 1 | Figure 1
Estructura de NMCPs y laminas. Ambas presentan una distribucin similar de coiled
coils (cajas naranja), regiones conservadas (barras verdes), sitios para cdk1 (barras
rojas), NLS (cajas verdes) y un segmento de aa cidos (caja roja). Las NMCPs carecen
de plegamiento Ig (elipse negra) y la caja CAAX de laminas pero tienen el extremo
C-terminal conservado. Regiones que dirigen las NMCP a la EN (*).
Financiacin | Funding
BFU2010-15900 (MINECO)
PIE 201020E019 (CSIC)
Structural analogies of NMCPs and lamins. Both display a similar distribution of coiled coils
(orange boxes), conserved regions (green bars), cdk1 phosphorylation sites (red bars), a NLS
(green boxes) and a stretch of acidic aminoacids (red boxes). NMCPs lack the Ig fold (black
ellipse) and the CAAX box of lamins, but have a conserved C-terminus. Regions mediating NE
localization of NMCPs (*).
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The plant lamina and its main interacting partners. The NMCP-based lamina binds to NPCs through Nup136 and NUA, and associates to nucleocytoplasmic linkers by binding of NMCPs to SUNs
and plant specific KASH proteins (WIP). These complexes connect the lamina with the actin cytoskeleton and the -TuC complexes but also anchor proteins to the ONM (RanGAP). Not elucidated
interactions (?).
Nuclear Matrix
and Regulation
of the Nuclear
Organization and
Function
Our aim is the analysis of the plant nuclear lamina.
We have determined the functional analogs of
metazoan lamins in plants, the NMCP protein
family and analyzed the two homologs MMCP1 and
NMCP2 in the monocot Allium cepa, as well as their
interactions with SUN proteins that are the only
lamin-binding proteins conserved in plants and form
the protein complexes that link the nucleoskeleton
and cytoskeleton in metazoan and plants.
Publicaciones Seleccionadas
Selected Publications
Ciska M, Moreno Diaz de la Espina S [2014] The intriguing plant nuclear lamina.
Front Plant Sci. 5, 166. DOI: 10.3389/fpls.2014.00166.
Gasset-Rosa F, Coquel AS, Moreno-del lamo M, Chen P, Song X, Serrano AM,
Fernndez-Tresguerres ME, Moreno-Daz de la Espina S, Lindner AB, Giraldo R
Figura 2 | Figure 2
La lmina vegetal y sus principales interacciones. La lmina de protenas NMCP se une a los PNC a traves de Nup136 y NUA, y se asocia a los complejos que conectan ncleo y
citoplasma por unin de las NMCPs a SUNs y protenas KASH especficas (WIP). Estos complejos conectan la lmina con el citoesqueleto de actina y los complejos -TuC pero
tambin anclan protenas a la MNE (RanGAP). Interacciones no aclaradas (?).
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Investigador Cientfico
jlbarbero@cib.csic.es
PhD, 1981
Universidad Complutense de Madrid
Lucas Snchez
Rodriguez
Profesor de Investigacin
lsanchez@cib.csic.es
PhD, 1976
Universidad Complutense de Madrid
Postdoctoral, 1977-1979
Investigador Asociado, 1979-1981
Zoological Institute University of Zurich
Researcher, 1983-1996
Pharmacia/Antibioticos Pharma
Dinmica Cromosmica
en Meiosis
El complejo de cohesinas y el control de la dinmica
de dicho complejo en la cromatina son esenciales
para la correcta segregacin cromosmica. Errores
en estos mecanismos conducen a la muerte celular,
patologas como el sndrome de Down, la formacin
de tumores, la infertilidad y otras cohesinopatas.
Chromosomal Dynamics
in Meiosis
Are there link between human syndromes with
physical and mental problems, a tumor growing out
of control and the incapability to contribute to next
generation? This question can be answered if we
look at the biological functions of a protein complex,
named cohesin.
Publicaciones Seleccionadas
Selected Publications
Barbero JL [2013] Cohesin Complexes: Modulators of Chromatin Organization
Control Gene Expression in Immune System. In: Advances in Medicine and
Biology Vol. 58.pp. 167-176. Editor: Leon V. Berhardt. Nova Science Publisher,
Inc. New York. USA. ISBN: 978-1-62257-803-0.
Calvente A, Viera A, Parra MT, de la Fuente R, Suja JA, Page J, Santos JL, Garca de la
Vega C., Barbero JL, Rufas JS [2013] Dynamics of cohesin subunits in grasshopper
meiotic divisions. Chromosoma 122: 77-91.(DOI 10.1007/s00412-012-0393-6).
Roco Gmez, Alberto Viera, Ins Berenguer, Elena Llano, Alberto M. Pends, Jos
Luis Barbero, Akihiko Kikuchi and Jos A. Suja [2014] Cohesin removal precedes
topisomerase II -dependent decatenation at centromeres in male mammalian
meiosis II. Chromosoma. 123:129-146. DOI 10. 1007/s00412-013-0434-9.
Figura 1 | Figure 1
Implicacin del complejo de cohesinas y sus reguladores en las patologas humanas
denominadas cohesinopatas.
Cohesin and cohesin regulators in human cohesinopathies.
Financiacin | Funding
Bases Moleculares de la Aneuploida en Cncer: Control de la Segregacin
y Estabilidad Cromosmica. AP 98712012 (2012-2014) FUNDACIN DE
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Caburet S., Arboleda VA, Llano E., Overbeek PA, Barbero JL, Oka K., Harrison W.,
Vaiman D., Ben-Neriah Z., Garcia-Tuon I., Fellous M., Pends AM, Veitia RA and
Vilain E [2014] Mutant Cohesin in Premature Ovarian Failure. New England J.
Med. 370:943-949.
Llano E., Gmez-H L.,Garca-Tuon I., Snchez Martn M., Caburet S., Barbero JL,
Schimenti JC, Veitia RA and Pends AM [2014] STAG3 is a strong candidate gene
for male infertility. Human Mol. Genet. 23:3421-3431.
Ruiz, M.F., Sarno, F., Zorrilla, S., Rivas, G. and Snchez, L. (2013) Biochemical and
functional analysis of Drosophila-Sciara chimeric Sex-lethal proteins. PLoS ONE
8(6): e65171.
Snchez, L. (2014) Sex determining mechanisms in insects based on imprinting
and elimination of chromosomes. Sexual Development 8: 83-103.
24/6/15 12:54
PhD, 2005
Universidad Complutense de Madrid
Postdoctoral, 2005-2009
MRC-Laboratory of Molecular Biology
(Cambridge, UK)
Postdoctoral, 2009-2012
Investigadora Ramn y Cajal, 2012
CIB, CSIC
Publicaciones Seleccionadas
Selected Publications
Oliva MA, Martin-Galiano AJ, Sakaguchi Y, Andreu JM [2012] Tubulin homolog TubZ
in a phage partition system. Proc Natl Acad Sci USA 109 (20):7711-6.
http://www.cib.csic.es/en/grupo.php?idgrupo=43
Financiacin | Funding
RYC-2011-07900 (Ministerio de Ciencia e Innovacin)
Tubulinas y FtsZ:
Modulacin del
Ensamblaje de Protenas
Bases moleculares de la segregacin de factores de
virulencia por sistemas de particin tipo III.
Postdoctoral, 1999-2000
Centro di Ricerca di Risonanze Magnetiche,
CERM (Florencia, Italia)
Postdoctoral, 2001-2002
Investigador I3P, 2003-2005
Investigador contratado, 2006-2009
Investigador Ramn y Cajal, 2010
CIB, CSIC
http://www.cib.csic.es/lignina/lignina_en.html
Financiacin | Funding
RYC-2009-04798
KBBE-2010-4-265397 (EC FP7)
BIO2011-26694 (MICINN)
Biotecnologa para la
Biomasa Lignocelulsica
Bsqueda e ingeniera de nuevas peroxidasas
fngicas de alto potencial redox.
Oliva MA, Andreu JM [2014] Tubulin and FtsZ superfamily of protein assembly
machines. (review) In: eLS, Encyclopedia of Life Sciences (e-Book chapter;
John Wiley & Sons, Ltd. Chichester) doi: 10.1002/9780470015902.a0025586.
Andreu JM, Oliva MA [2013] Purification and assembly of bacterial tubulin BtubA/B
and constructs bearing eukaryotic tubulin sequences. Methods in Cell Biology
115, 269-281.
Publicaciones Seleccionadas
Selected Publications
Barrasa JM, Blanco MN, Esteve-Ravents F, Alts A, Checa J, Martnez AT, RuizDueas FJ [2014] Wood and humus decay strategies by white-rot basidiomycetes
correlate with two different dye decolorization and enzyme secretion patterns on
agar plates. Fungal Genet Biol 72: 106-114.
Ruiz-Dueas FJ, Lundell T, Floudas D, Nagy LG, Barrasa JM, Hibbett DS, Martnez
AT [2013] Lignin-degrading peroxidases in Polyporales: an evolutionary survey
based on ten sequenced genomes. Mycologia 105: 14281444.
Biotechnology for
Lignocellulosic Biomass
Screening and engineering of new high redoxpotential fungal peroxidases.
ur research activity aims to obtain novel peroxidases with catalytic properties of interest that can be used in industrial oxidation processes, substituting harsh chemical reagents. To attain
this objective, a strategy has been designed consisting of searching
for genes encoding new type-peroxidase enzymes in fungal genome
sequences, and subsequent tailored designing of their catalytic properties and stability by using protein engineering techniques.
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