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April 01 - April 30

5 entries found

Human pluri..
Start date: April 09
04:00 pm 05:00 pm

Description: 

Information about the research of Dr. Goureau:

Our research group aims at understanding retinal differentiation mechanisms and at participating in cell therapy by developing new approaches based on retinal cell regeneration. Our main research fields include the use of human induced pluripotent stem (iPS) cells in cell-based rescue or replacement strategies and in human retinal disease modeling. Our objectives are: i) the development of innovative and robust protocols allowing the differentiation of human iPS cells into different retinal cell types (retinal ganglion cells, photoreceptors and RPE cells) and the ii) derivation of iPS cells from patients affected by specific inherited retinal dystrophies to understand retinal pathological mechanisms and to further develop large-scale drug screening.


Selected publications:

From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium. Reichman S, Terray A, Slembrouck A, Nanteau C, Orieux G, Habeler W, Nandrot EF, Sahel JA, Monville C, Goureau O. Proc Natl Acad Sci U S A. 2014

Involvement of Bcl-2-associated transcription factor 1 in the differentiation of early-born retinal cells. Orieux G, Picault L, Slembrouck A, Roger JE, Guillonneau X, Sahel JA, Saule S, McPherson JP, Goureau O. J Neurosci. 2014

Ciliary neurotrophic factor promotes muller glia differentiation from the postnatal retinal progenitor pool. Goureau O, Rhee KD, Yang XJ. Dev Neurosci. 2004

Inducible nitric oxide synthase mediates the change from retinal to vitreal neovascularization in ischemic retinopathy. Sennlaub F, Courtois Y, Goureau O. J Clin Invest. 2001 Mar;107(6):717-25.

Differential regulation of inducible nitric oxide synthase by fibroblast growth factors and transforming growth factor beta in bovine retinal pigmented epithelial cells: inverse correlation with cellular proliferation. Goureau O, Lepoivre M, Becquet F, Courtois Y. Proc Natl Acad Sci U S A. 1993

Modulation ..
Start date: April 15
03:00 pm 04:00 pm

Complex mul..
Start date: April 17
11:00 am 12:00 pm

Description: 

Current chromatin conformation capture methods require the ligation of two restriction-digested DNA ends to identify an interaction between genomic loci, which limits their ability to identify contacts between more than two loci interacting simultaneously in the same cell. Other limitations include the variable efficiency of chromatin crosslinking and of restriction digestion, which complicate the interpretation of observed contacts.
We present a new ligation-free method for determining chromatin interactions on a genome-wide scale, which is capable of detecting simultaneous interactions between three or more genomic loci.
We generate a genome-wide dataset of chromatin interactions in mouse ES cells using our new method. Using a tailor-made statistical model, we identify preferential chromatin contacts across large genomic distances. Importantly, we observe especially prominent interactions between enhancers and active genes. By exploiting the unique ability of our method to interrogate high-multiplicity interactions, we are able to detect a striking pattern of abundant, simultaneous three-way contacts genome-wide. Our work highlights that simultaneous association of multiple regulatory regions is an under-appreciated feature of genome architecture.


Publications:

Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs.

Brookes E, de Santiago I, Hebenstreit D, Morris KJ, Carroll T, Xie SQ, Stock JK, Heidemann M, Eick D, Nozaki N, Kimura H, Ragoussis J, Teichmann SA, Pombo A.

Cell Stem Cell. 2012 Feb 3;10(2):157-70. doi: 10.1016/j.stem.2011.12.017.

 

Proteomic analysis of mitotic RNA polymerase II reveals novel interactors and association with proteins dysfunctional in disease.

Möller A, Xie SQ, Hosp F, Lang B, Phatnani HP, James S, Ramirez F, Collin GB, Naggert JK, Babu MM, Greenleaf AL, Selbach M, Pombo A.

Mol Cell Proteomics. 2012 Jun;11(6):M111.011767. doi: 10.1074/mcp.M111.011767. Epub 2011 Dec 22.

 

 

Complexity of chromatin folding is captured by the strings and binders switch model.

Barbieri M, Chotalia M, Fraser J, Lavitas LM, Dostie J, Pombo A, Nicodemi M.

Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16173-8. doi: 10.1073/pnas.1204799109. Epub 2012 Sep 17.


Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells.

Stock JK, Giadrossi S, Casanova M, Brookes E, Vidal M, Koseki H, Brockdorff N, Fisher AG, Pombo A.

Nat Cell Biol. 2007 Dec;9(12):1428-35. Epub 2007 Nov 25.

Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations.

Branco MR, Pombo A.

PLoS Biol. 2006 May;4(5):e138. Epub 2006 Apr 25.

IL-8 intera..
Start date: April 17
04:00 pm 05:00 pm

Description: 

Interactions of glycosaminoglycans (GAGs) with their protein targets, such as chemokines and growth factors, are crucial for cell communication processes. Therefore, an elaborate characterization of these interactions is of a great interest for developing strategies for engineering novel biomaterials for tissue regeneration. There is experimental evidence that the function of interleukin-8 (IL-8) is strongly influenced by interactions with GAGs. However, molecular mechanisms underlying IL-8/GAG interactions are unknown, and no experimental structures of IL-8/GAG complexes are available. We use computational approaches (docking, molecular dynamics, free energy calculations) linked to experimental techniques (NMR, mutagenesis, surface plasmon resonance, fluorescence) to elucidate details of molecular mechanisms underlying IL-8/GAG recognition. We have predicted and analyzed the binding pose of different GAGs to IL-8. Our predictions have been confirmed by NMR. We have used use our theoretical models to determine the energetic impact of individual IL-8 residues for GAG binding and to propose experiments to determine the role of those residues. We have designed a mutant IL-8E75K, for which we have identified a new GAG binding pose that is not favourable for the wild type and that agrees with our NMR data. We have designed N- and C-terminally truncated IL-8 variants and analyzed them in terms of their abilities to dimerize and bind GAGs. Our data assist in a better understanding of the IL-8/GAG interactions exhibiting an example of how computational and experimental techniques can benefit from each other in analysis of protein/GAG interactions.

Bone - a dy..
Start date: April 24
11:00 am 12:00 pm

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