Pamela and Patricia Presenting @ Student Seminar on 3.26.09

Student Seminar is upon us again and we will have Pamela Pretorius and Patricia Schneider presenting on Thursday @ noon in 2289 CBRB.  As usual I have asked them both to provide me some background information to bring us all up to speed regarding their past research.  See you Thursday.

Background for Pamela’s Presentation:Pamela_Pretorius

Visual impairment and blindness have far reaching implications for society. In 2002, a study by the World Health Organization (WHO) found that 161 million people worldwide suffered from visual impairment, making vision loss and blindness not only a personal burden but also a global burden. Hundreds of individually rare, but collectively common Mendelian disorders can cause blindness. One of those disorders is a heterogeneous syndromic form of retinal degeneration, Bardet-Biedl Syndrome (BBS). A pleiotropic disorder, BBS is characterized by obesity, retinitis pigmentosa, polydactyly, renal abnormalities, hypogenitalism and cognitive impairment. In addition, BBS is also associated with an increased susceptibility to hypertension, diabetes mellitus and heart defects. Although BBS is a rare disorder in the general population, some components of the BBS phenotype, such as obesity, diabetes and blindness, are common in the general population. BBS is a syndromic form of retinitis pigmentosa (RP).  A syndromic form of retinitis pigmentosa (RP), individuals with BBS experience central vision loss during childhood or early adolescence and are blind by the second or third decade of life.

Our lab has established both the mouse and zebrafish as models to further study both cellular and molecular events underlying this retinal degeneration.  We have generated five knockout lines as well as a knockin mouse for BBS and all recapitulate the human BBS phenotype of retinal degeneration.  Interestingly, death of the photoreceptors is preceded by mislocalization of rhodopsin, suggesting that there is a defect in intracellular transport in Bbs mutant mice.  Additionally, we have adapted a cone-based vision assay to test visual acuity in the zebrafish.

The focus of my project is to evaluate the molecular and biological processes behind the retinal degeneration observed in the human disease Bardet-Biedl Syndrome (BBS) with respect to two BBS3 (NCBI, UCSC) transcripts.paty-and-anna

Background for Patricia’s Presentation:

I have a special interest in understanding how Wnt signaling controls the formation of the embryonic axis in vertebrates. I use the zebrafish and Xenopus laevis to unravel the mechanisms behind axis formation. In our lab, we utilize gene knockdown as well as transgenic lines to dissect the function of members of this signaling pathway during embryonic stages.

The Wnt signaling network has critical roles in cell proliferation, differentiation morphogenesis and stem cell biology. Complexity of the Wnt signaling network is apparent in early embryonic development. For instance, activation of maternal Wnt signaling is essential for dorsal specification, whereas inhibition of zygotic Wnt signaling is required for patterning of the anterior-posterior axis. Modulation of β-catenin protein levels is central to the function of Wnt signaling. In the absence of a class of Wnt ligands, a degradation complex including Axin, adenomatous polyposis coli (APC) and glycogen synthase kinase 3 (GSK3) stimulates the phosphorylation and degradation of β-catenin. In the presence of a class of Wnt ligands, Dishevelled (Dsh) protein is activated, recruits Axin to the plasma membrane and inhibits the degradation complex, allowing β-catenin to accumulate. β-catenin can then translocate to the nucleus interact with cofactors and activate transcription.

Axin is a key player in the degradation complex, as it serves as the scaffold for proteins involved in the phosphorylation of β-catenin. Axin contains four critical domains: a β-catenin binding domain, a GSK3 binding domain, a Regulator of G-protein (RGS) domain and a DIX domain (protein interaction domain shared with Dsh). RGS domains are typical of RGS proteins, which were originally identified as regulators of the active half-life of G-protein signaling. However, it is not known whether the Axin-RGS domain functions in G-protein signaling. My work focuses on the function of the Axin-RGS domain during maternal and zygotic stages.p_schneider-images1

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Posted on March 23, 2009, in Student Seminar and tagged , , , , , , , , , , , , , , , , , , , , , . Bookmark the permalink. Leave a comment.

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