Yan and John to present at Student Seminar on Thursday (17.March) at11:45 in 2-501

Yan and John  will be presenting Student Seminar this week in 2-501 BSB at 11:45. I have had both speakers provide background on their talk.  Please note the earlier start time, this is to allow time for Tinaa Tootle and Sarit Smolikove to solicit feedback on the Genetics web site.   Hope to see you there, this is a Student Seminar not to miss!

Background for Yan’s talk

Functional Analysis of Cep290

Purpose: CEP290 is a large, multi-domain protein implicated in several cilia related syndromic disorders including Meckel-Gruber, Joubert, Senor-Loken and Bardet-Biedl Syndrome (BBS). Moreover, CEP290 is the most frequently mutated gene underlying the non-syndromic blinding disorder, Leber’s congenital amaurosis (LCA). The Purpose of the current study is to characterize the function of various CEP290 domains and to characterize a zebrafish model aimed at progressing towards future therapy for patients with CEP290 LCA.

Methods:  We generated several truncated CEP290 protein fragments, which comprise several domains of the whole protein. We tagged these fragments with GFP and examined their localization in 293T and RPE cells. We also evaluated the physical interaction between these truncated proteins and other cilia proteins by co-immunoprecipitation. To determine the in vivo function of cep290 in the zebrafish, we examined the effects of cep290 knockdown using an antisense oligonucleotide (Morpholino, MO) designed to generate an altered cep290 splice product that models a common LCA mutation.

Results: The N-terminal and C-terminal fragments of CEP290 both localize to the centrosome. The N-terminus  interacts with NPHP2 and NPHP5, whereas the C-terminus interacts with MKS1. Histological analysis of the retina of cep290 knockdown zebrafish revealed no gross morphological defects; however, knockdown of cep290 results in a statistically significant reduction in visual function. We tested whether truncated CEP290 proteins could rescue the cep290 MO knockdown phenotype in zebrafish by co-injection of RNA with the cep290 MO. We demonstrate that vision impairment caused by disruption of cep290 can be rescued by expressing the N-terminus protein fragment.

Background for John’s talk

Genetic Fine Mapping of Metabolic Syndrome in Lyon Hypertensive Rats

Lyon Hypertensive rats (LH) is an established animal model for metabolic syndrome. Previous research has demonstrated that the chromosome 17 of LH harbours QTLs for several metabolic syndrome phenotypes, including hypertension and dyslipidemia. In order to more accurately select candidate genes for the LH phenotype, we are using SNP discovery to perform fine mapping of the established major haplotypic region on chromosome 17. In this presentation I will discuss the current progress of this investigation.

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Posted on March 14, 2011, in Student Seminar and tagged , , , , . Bookmark the permalink. Leave a comment.

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