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| '''Functional Genomics of the Human Embryo'''
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| == Nuts and bolts == | | {|cellspacing="5" cellpadding="10" style="background:#000; width: 750px;" |
| Equipe Etchevers <br>
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| INSERM U781, Tour Lavoisier, 2ème étage<br>
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| Hôpital Necker - Enfants Malades<br>
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| 149, rue de Sèvres<br>
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| 75743 Paris Cedex 15<br>
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| France<br>
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| tel: (+33) 1 44 49 40 00 poste 97838<br>
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| fax: (+33) 1 44 49 51 50
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| • [http://www.necker.fr/irnem/membres_equipes.asp?id=135 External web page with phone extensions]<br>
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| Although Heather is also working 80% at the [http://www.u563.toulouse.inserm.fr/ INSERM U563], Centre de Physiopathologie de Toulouse - Purpan until 2009, the lab is still at the above address.
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| | <center> |
| | == Embryological bases of congenital malformations == |
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| == Research ==
| | We are a small group of scientists working on human neural crest stem cells and their differentiated progeny in the head and thoracic region. Read all about it, and us, using the links above. |
| === Human neural crest cell differentiation ===
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| Our current project concerns the transcriptional and phenotypic characterization of highly multipotent neural crest cells (NCC) derived from human embryos. Such characterization is a prerequisite to developing cell-based replacement therapies for congenital malformations or progressive diseases in which neural crest-derived lineages play a primary pathogenic role (“neurocristopathies”).
| | Like nested dolls, our group was, until July, 2010, part of [http://www.necker.fr/u781/Team_1.html a larger team] interested in the genetic bases of congenital diseases and malformations. That team, with some of our original members, remains part of the [http://www.necker.fr/u781 research unit #781], dedicated to "Genetics and Epigenetics of Neurometabolic Diseases and Birth Defects" (also [http://www.necker.fr/irnem/units/detail.php?id=8 see here]). |
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| A quantitative SAGE analysis of the entire set of mRNA transcripts derived from primary human NCC has been completed in our laboratory, in order to establish the transcriptional profile of genes that distinguish the undifferentiated state for this cell type. The SAGE data is being supplemented with that from a different functional genomics tool that is being exploited in our parent research group in the INSERM U781 and with our collaborators at Institut Curie, Affymetrix DNA microarrays. Statistical analysis and comparison of the SAGE and microarray results using bioinformatics allows us to class transcripts into functional clusters and identify groups of genes that are up- or down-regulated during NCC differentiation.
| | I am developing new subtopics and accepting students within the [http://www.zaffranlab.com/ Genetics, patterning and cardiovascular diseases] group, which is part of the [http://umr910.timone.univ-mrs.fr/ Unité Mixte de Recherche 910] (with contributions from the [http://www.univmed.fr/fr/faculte-medecine Université Aix-Marseille II]) in Marseille. |
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| In order to rapidly assess gene function, our group looks at the expression of candidate genes for certain neurocristopathies during normal human embryonic development using '' in situ '' hybridization on sections. We can also test the effects of gain or loss of gene function by targeting the NCC of the chicken embryo (a model with many technical advantages) using electroporation, and performing short- and long-term analyses.
| | We are all, nonetheless, part of the French equivalent to the intramural program of the U.S. [http://www.nih.gov/ N.I.H.], the Institut national de la santé et de la recherche médicale ([http://www.inserm.fr/ INSERM]). |
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| Over the long term, our group also plans to immortalize human NCC shortly after their initial migration, when they most resemble “true” stem cells in their potential. We will test the capacity of the cells to differentiate appropriately after transplantation '' in vivo '' into the developing chicken embryo. In this way, we can define the capacity of multipotent NCC to acquire diverse cell phenotypes in an appropriate environment.
| | (Links out updated May 7, 2012.) |
| | | *'''[[User:Etchevers|Heather]] 10:01, 7 May 2012 (EDT)''': |
| Our group is particularly interested in neurocristopathies of the cephalic pole, including eye malformations of the anterior chamber, congenital heart defects, and in the congenital giant naevus.
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| === Différenciation de la crête neurale humaine ===
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| '' Notre projet concerne la caractérisation transcriptionnelle et phénotypique des cellules multipotentes de la crête neurale (CN) dérivée d’embryons humains. Cette recherche est indispensable avant d’envisager de développer des cytothérapies de remplacement pour des « neurocristopathies » congénitales ou progressives tels le syndrome de Hirschsprung ou certaines neuropathies périphériques.''
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| '' Nous entreprenons d’immortaliser des lignées de CN humaine peu de temps après la migration initiale de ces cellules, quand ils ont le plus grand potentiel de différenciation. Nous allons tester la capacité des lignées de se différencier correctement'' in vivo '' chez l’embryon de poulet. Une analyse quantitative SAGE du transcriptome entier des cellules CN humaines vient de terminer, afin d’établir le profil des gènes qui caractérisent l’état indifférencié de la CN.''
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| '' Enfin, nous corroborons ces résultats avec un autre outil de génomique fonctionnel, des puces Affymetrix, utilisés par les collaborateurs de l’équipe 2 de l’INSERM U781 et à l’Institut Curie. Nous comparons par exemple le profil transcriptionnel des ganglions fœtaux avec celui de leurs précurseurs multipotents. Une analyse statistique et une comparaison bio-informatique des résultats SAGE et microarray nous permet de classer les transcrits par groupes fonctionnels qui sont modulés au cours de la différenciation.''
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| '' Afin d’évaluer rapidement la fonction de tels groupes, nous examinons l’expression de gènes candidats pour des neurocristopathies humaines par l’hybridation'' in situ '' sur des coupes d’embryons humains normaux. Nous effectons aussi des gains ou pertes de fonction de ces gènes au sein de la CN de l’embryon de poulet afin de voir l’effet sur sa différenciation dans un environnement approprié. Ainsi, nous espérons identifier des nouveaux gènes responsables de neurocristopathies ainsi que de connaître leurs modes de fonctionnement qui pourront mener à des voies thérapeutiques.'' | |
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| '' Le groupe s'intéresse particulièrement aux malformations congénitales qui touchent le pole céphalique, le coeur, la chambre antérieure de l'oeil et la peau.''
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| <div style="padding: .4em .9em .9em">
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| <h3>Current lab members</h3>
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| • [[User:Etchevers|Heather Corbett Etchevers]] <br>
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| • [[User:Thomas|Sophie Thomas]]<br>
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| • [[User:Golzio|Christelle Golzio]]<br>
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| • [[User:Quintyn|Jean-Claude Quintyn]]<br>
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| • [[User:Chassaing|Nicolas Chassaing]]<br>
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| <h3>Former lab members</h3>
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| • [[User:Goudefroye|Géraldine Mattei Goudefroye ]]<br>
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| • [[User:Detrait|Eric Detrait]]<br>
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| • [[User:Guedu|Geneviève Guédu]]<br>
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| • [[User:Baala|Lekbir Baala ]]<br>
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| <h3>Other important people</h3>
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| • Equipe #2 of [[User:INSERM_U781|INSERM U781]], Handicaps Génétiques de l'Enfant<br>
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| • [[User:Visitors_Avenir|Visitors]]<br>
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| </div>
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| <div style="clear: right; text-align: left; float: left; padding: .4em .9em .9em">
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| <h3>Local techniques</h3>
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| • [http://www.openwetware.org/images/5/5f/Recettes_PBS_et_PBT.pdf PBS-PBT recipes]<br>
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| • [[Etchevers:Extraction_ARN_francais|Extraction ARN total de tissus]]<br>
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| • [[Etchevers:ChIP_francais|Immunoprecipitation de la chromatine (francais)]]<br>
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| • [[ChIP|ChIP]] in English<br>
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| • <br>
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| <div style="clear: right; text-align: left; float: left; padding: .4em .9em .9em">
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| <h3>Trucs utiles</h3>
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| • Comment envoyer un Fedex<br>
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| • Paperasse autour de la radioactivité<br>
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| ----
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| • [http://www.openwetware.org/images/6/6a/Neural_crest_M1_2006.pdf Presentation (PDF) on neural crest development M1 2006]<br>
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| • <br>
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| </div>
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| </div>
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| |}
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| == [[Etchevers:Publications list| Publications]]: click on the word ==
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| [[Image:PinkRibbonLL.gif|right|frame]]
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| <p>We remember those who were our dear colleagues, friends and collaborators:</p>
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| • Christiane Ayer-Le Lievre<br>
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| • Patrizia Cameron-Curry<br>
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| • Marcy Speer<br>
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| --[[User:Etchevers|Alethea]] 05:02, 8 August 2007 (EDT)
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