Archive | February 2012

Moving in, moving out

With more than 1,400 people working at the PRBB, the movement of researchers coming and going is constant.

One of the most recent acquisitions is Eduard Sabidó, who has just arrived to be the new head of the CRG/UPF Proteomics Unit. Eduard is coming from the Swiss Federal Institute of Technology of Zurich (ETHZ)  and will be leading this core facility which offers service to the whole park and beyond.

A new young group leader has also joined the CRG recently. The French molecular biologist Guillaume Filion (who, as we mentioned in an earlier post, is currently looking for a postdoc) was last at The Netherlands Cancer Institute, in Amsterdam, where he did a postdoc during three years. His research group on Genome Architecture is focused on understanding the ‘regulatory genome’ – that is, the largest amount of the genome which does not code for proteins. We hope to be posting some more news on his research soon!

And while some come, others go… Hernán López-Schier and his group will sadly be leaving the Cell and developmental biology programme of the CRG in March. After nearly 6 years at the CRG, the Sensory Cell Biology and Organogenesis group is moving north to Munich. Hernán will become director of the Department of Sensory Biology & Organogenesis at the IDG – Helmholtz Zentrum München. There, the group will continue their research on the acquisition and maintenance of sensory-organ function, using the zebrafish as a model organism. Sabrina Desbordes, currently in this group, is also moving to the same institute to start her own group as a Junior Group Leader. Good luck to both of them!

Helping 3′ splice site recognition

Splicing is a complex mechanism that generates mature mRNA from pre-mRNA and which is essential for a correct gene expression. It involves many factors – nearly 400, if we consider alternative splicing as well – and it is tightly controlled. A new paper published in Molecular Cell by Juan Valcárcel, head of the Regulation of Alternative pre-mRNA Splicing group at the CRG, and colleagues has now identified an heterogeneous nuclear ribonucleoprotein (hnRNP) that helps in the recognition of the 3′ splice site.

The essential pre-mRNA splicing factor U2AF guides the early stages of splice site choice by recognizing a polypyrimidine (Py) tract consensus sequence near the 3′ splice site. The U2AF 65 KDa subunit binds to the Py tract while its 35 KDa subunit binds the invariant AG dinucleotide at the intron 3′ end.

Since Py tracts are relatively poorly conserved in higher eukaryotes, how does U2AF find the right ones?

By using in vitro and in vivo depletion, as well as reconstitution assays using purified components, the authors have identified hnRNP A1 as an RNA binding protein that allows U2AF to discriminate between pyrimidine-rich RNA sequences followed or not by a 3′ splice site AG.

Valcárcel and colleagues have demonstrated using biochemical assays and NMR that hnRNP A1 forms a ternary complex with the U2AF heterodimer on AG-containing/uridine-rich RNAs, while it displaces U2AF from non-AG-containing/uridine-rich RNAs.

 

Reference:
Tavanez JP, Madl T, Kooshapur H, Sattler M, Valcárcel J
hnRNP A1 Proofreads 3′ Splice Site Recognition by U2AF.
Mol Cell. 2012 Feb 10;45(3):314-29 

EMBO meeting on yeast gene transcription

The EMBO meeting on “Gene transcription in yeast: from mechanisms to gene regulatory networksaims to catalyze the transformation of the field from classical genetics, biochemistry and structural biology to functional genomics and molecular systems biology of gene transcription and regulation.

Organised by Francesc Posas, the director of the Department of Experimental and Health Sciences of the UPF, the meeting will take place in Girona on June 16-21, 2012. However, registration deadline is already on March 16, so don’t wait too long! You can already check out the programme on the conference website.

Make sure you don’t miss this opportunity!

The February issue of Ellipse is out

In the 51st edition of El·lipse, The Pasqual Maragall Foundation for Alzheimer’s research announces the location of its new building, a few meters from the PRBB. Xavier Nogués (IMIM) talks about his research on osteoporosis while Jean Michel Claverie, from the CNRS, tells us about his discovery of mimiviruses. Other news include articles on why a bit of stress can be protective for your cells; the existence of spleen neutrophils; how the fate of embryonic stem cells is controlled; new targets against Duchenne dystrophy; and the discovery of new anti-angiogenic compounds. Also, how does temperature control sex? And what are the pros and cons of patenting? Finally, find out which six researchers from the PRBB centres have been awarded the very prestigious ERC Advanced Grants and HHMI Early Career Awards.

You can read a multimedia version or the PDF. Enjoy!

Meeting on Systems biology of Drosophila development – register now!

Johannes Jaeger, from the CRG, is the chair of the ESF-EMBO Symposium “Systems Biology of Drosophila Development”, which will take place in May 21-25 in Poland. Co-chaired by Eileen Furlong, at the EMBL, the meeting will bring together experimentalists, computational biologists and theoreticians, who have made outstanding contributions to the study of Drosophila development. The aim is to enable researchers with different backgrounds and expertise to share their experiences and latest research, to discuss methodological issues, to identify problems with existing models, and to discuss new developmental processes, which would be worth studying using a systems-biology approach.

Conference registration is possible only after successful application (please click here to apply), and the  deadline for application is approaching fast: February 13, 2012. Only four days to go… make sure you don’t miss this interesting opportunity!

Postdoc position on cell and molecular biology at the CRG

A postdoctoral position is available in the group of Pedro Carvalho at the CRG. The Organelle biogenesis and homeostasis lab studies the molecular mechanisms by which misfolded secretory and membrane proteins are detected and eliminated from cells. The succesful candidate will work on protein quality control.

Application deadline is February, 29, 2012. Starting date would be no later than May 2012.

Details: Postdoc position

Bioinformatician position at the laboratory of Miguel Beato

Miguel Beato’s laboratory at the CRG on chromatin and gene expression is looking for a bioinformatician to give support to the members of the CONSOLIDER project “Epigenetic: Mechanisms and Disease”. The work would consist in developing and applying existing and newly developed bioinformatic and statistical tools to analyze genome-wide data (3C-derived methods, RNA-seq, ChIP-seq, MNase-seq, DNase I hypersensitive sites, CpG methylation and hydroxy-methylation assays) in cultured cells.

Application deadline is February 20, 2012. Initial contract is for six months starting March 2012, with the possibility of extension into a more stable position.

Details: Bioinformatician position

Effects of chemical exposure and social environment on the developing brain

The developing brain is exceptionally sensitive to environmental influences, and two recent papers lead by scientists at the CREAL have analysed the effect of several variables – chemical exposure and social environment – in neurodevelopment of infants. In the specific cases studied, the effect didn’t seem to be very substantial.

One of the articles was published in the American Journal of Epidemiology, and it focuses on the potential effect of prenatal exposure to mercury, since it is known that vulnerability of the central nervous system to this metal is increased during early development. The scientists examined 1,683 children who are part of the INMA (Environment and Childhood) Project from 4 regions of Spain between 2003 and 2010. The mercury levels at the cord blood were analyzed by atomic absorption spectrometry, and infant neurodevelopment was assessed around age 14 months by the Bayley Scales of Infant Development – a standard series of measurements originally developed by psychologist Nancy Bayley and which are used to assess the motor, language, and cognitive development of children aged 0-3.

Although the maternal-birth cohort studied comes from moderate-high fish consumption areas, and mercury is found primarily in fish, even a doubling in total mercury levels did not show an association with mental or psychomotor developmental delay. When findings where stratified by sex, there was a slight negative association between prenatal exposure to total mercury and psychomotor development among female infants, but the researchers admit that follow-up is required to confirm these results.

The second paper, published in Gaceta Sanitaria, wanted to examine the effect of maternal intelligence and mental health, taking into account also maternal occupational social class and education, on the neuropsychological development of their children. The subjects studied were also from the INMA project and the children were, again, analysed at 14 months. The mothers’ intelligence and mental health were assessed by professional psychologists and standard tests and questionnaires.

The authors found that maternal IQ plays an important role in the first stages of cognitive development in children in the more disadvantaged occupational social classes. For the other groups, the effects of maternal IQ on cognitive development were mostly explained by maternal education. As per maternal mental health, it had no effect on the childrens’ neurodevelopment, although the authors say this might be because the study was performed in a non-clinical population in which mothers were not suffering from any other serious depressive or psychiatric disorders.

References:
Llop S, Guxens M, Murcia M, Lertxundi A, Ramon R, Riaño I, Rebagliato M, Ibarluzea J, Tardon A, Sunyer J, Ballester F, on Behalf of the INMA Project. Prenatal Exposure to Mercury and Infant Neurodevelopment in a Multicenter Cohort in Spain: Study of Potential Modifiers. Am J Epidemiol. 2012 Jan 27;

Forns J, Julvez J, García-Esteban R, Guxens M, Ferrer M, Grellier J, Vrijheid M, Sunyer J. Maternal intelligence-mental health and child neuropsychological development at age 14 months. Gac Sanit. 2012 Jan 26;

Polycomb switch in stem cell differentiation

The cover of the January issue of the journal Cell Stem Cell highlights the article: “Nonoverlapping functions of the polycomb group Cbx family of proteins in embryonic stem cells” by Luciano Di Croce and colleagues at the CRG. Although it is known that polycomb complexes (PRC) play an important role in the regulation of embryonic stem cell (ESC) pluripotency and early developmental cell fate decisions, this research has now shown that different Cbx protein compositions of the complex can modulate this regulation.

In pluripotent cells, Cbx7 is the main PRC1-associated Cbx protein and is required to maintain the undifferentiated state in a robust manner by repressing a large number of genes involved in lineage specification. The expression of Cbx7 diminishes as ESCs differentiate, most likely due to the reduction of the transcription factor Oct4, a marker of undifferentiated cells. As a consequence, during differentiation different task-specific PRC1 complexes are formed with Cbx2, 4, 6 or 8 proteins replacing the Cbx7 protein. Cbx4, for example, regulates the epidermal stem cell differentiation.

“We discovered that implanting ESCs depleted for the different specific Cbx proteins led to mice developing tumors with different characteristics. This showed that each Cbx protein has a unique function. Even though there is no medical application at the present time, these results will surely generate research towards developing anti-tumoural drugs that could block these type of proteins”, says Di Croce.

Reference:
Morey L, Pascual G, Cozzuto L, Roma G, Wutz A, Benitah SA, Di Croce L. Nonoverlapping functions of the polycomb group cbx family of proteins in embryonic stem cells. Cell Stem Cell. 2012 Jan 6;10(1):47-62

Genomic high-throughput sequencing data: what to trust

Does your research imply having to deal with a huge amount of high-throughput data? Are you worried about the interpretation of your Illumina sequencing data? Illumina’s Genome Analyzer (GA) and HiSeq instruments are currently the most widely used sequencing devices. If you use them or are thinking of using them, you might be interested in having a look at the latest paper coming from Heinz Himmelbauer and his colleagues at the CRG ultrasequencing unit and published in Genome Biology. Find out about the errors and biases they report to make sure your data analysis is of the highest quality!

Reference:
Minoche AE, Dohm JC, Himmelbauer H. Evaluation of genomic high-throughput sequencing data generated on Illumina HiSeq and Genome Analyzer systems. Genome Biol. 2011 Nov 8;12(11):R112 [PDF]

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