Yan and Heather to present at Student Seminar on Thursday (22.July) at noon in 1-107 BSB
Background for Yan’s talk
“Mutation in Cep290 results in higher fat percent in mice and centrosome splitting in kidney cells”
CEP290 (OMIM) is a large, multi-domain gene implicated in several cilia related syndromic disorders including Meckel-Gruber (OMIM), Joubert (OMIM), Senor-Loken (OMIM) and Bardet-Biedl Syndrome (BBS, OMIM). Moreover, CEP290 is the most frequently mutated gene underlying the non-syndromic blinding disorder Leber’s congenital amaurosis (LCA, OMIM).
We used one mouse line, rd16, which exhibit early-onset retinal degeneration with autosomal recessive inheritance due to an in-frame deletion in Cep290 from exon 35 to 39. This mutant protein alters the distribution of RPGR, rhodopsin and arrestin in the retina, suggesting a function of Cep290 in protein transport across the cilium. We checked body weight and fat percent of rd16 versus wt, and found that the fat percent of rd16 female mice is bigger than that of wt female mice though they are similar in body weight. Also, we found centrosome splitting in the rd16 kidney cells.
Background for Heather’s talk
“A screen for genes involved in synaptonemal complex disassembly”
The synaptonemal complex (SC) is a highly conserved structure formed between parental chromosomes during meiosis. In the absence of a properly formed, fully functional SC, mis-segregation of chromosomes occurs, leading to nondisjunction events. The outcome of such events hinders development and can lead to embryonic lethality. While a few of the SC structural proteins have been discovered, the mechanisms of assembly and disassembly remain elusive.
In our lab, we use C. elegans (Wormbase) as a model to study meiosis, focusing on the process of SC disassembly. Meiosis in C. elegans is easily studied thanks to a wealth of genetic and cytological tools available. Additionally, meiosis is surprisingly similar between these nematodes and humans. While we use a variety of genetic tools to study the disassembly process, my project utilizes RNAi methodology as means of discovering novel genes associated with the SC and it’s disassembly pathway. Prior screens conducted in our lab have uncovered a novel mutant, sda-1(rj1) which shows meiotic defects specific to SC disassembly. My current project involves an RNAi screen, searching for enhancers/suppressors of the sda-1 phenotype in hopes of identifying novel proteins via their interaction in the sda-1 pathway.
I have already screened several plates on chromosome II (4% of the RNAi library). In this pilot, we identified three suppressors and seven enhancers that were sda-1(rj1)– specific. Eight of these genes have not shown an embryonic lethal phenotype in other screens, including wild-type screens, thus indicating that we are capable of identifying novel genes with this method. Additionally, we have recovered SCC-1, a known meiotic/mitotic gene involved in chromosome segregation, which was not recovered in RNAi screens on the wild-type background, further proving the effectiveness of our screen.
Because of the conservation of the SC and meiosis, this work has a direct impact on human reproductive health. The power of C. elegans model system for studying meiosis is unparalleled by any other model organism. It allows us to study at the molecular level the mechanisms of chromosome segregation, leading to a greater overall understanding of meiosis. The knowledge gained from these types of studies can be translated into clinical techniques for prenatal screening, treatment, or prevention of nondisjuction related birth defects in humans.