Heather Brockway and Tryphena Cuffy to present their research on July 12th 2012

Heather Brockway’s research summary

Meiosis, worms and flies oh my!

A conserved role for Akirin in eukaryotic meiosis.

The production of gametes, sperm and eggs, requires the specialized cell division termed meiosis. Missegregation of chromosomes during meiosis is the leading cause of aneuploidy in humans, which can result in miscarriage or children with developmental disabilities. The synaptonemal complex (SC) plays a critical role during meiotic prophase I. It provides the essential physical link between the homologous pairs of chromosomes, which ensures proper meiotic chromosome segregation. Precise regulation of both assembly and disassembly of the SC is essential for proper chromosome segregation. The basic molecular mechanisms of SC disassembly are unknown.

The aim of this study is to elucidate the underlying molecular mechanisms of SC disassembly. The Smolikove lab has isolated a novel C. elegans mutant in a gene called akirin, which specifically affects SC disassembly, resulting in embryonic lethality. Our work is the first to establish a role for Akirin in meiosis. Our central hypothesis for this project is that Akirin’s role in SC disassembly during meiosis is evolutionarily conserved. As SC disassembly is best understood in Drosophila melanogaster, we will test our hypothesis by elucidating the mechanism of Akirin function during Drosophila meiosis using various genetic, cytological and molecular biology approaches.

Tryphena Cuffy’s research summary

Utilzing The Lystbg-J Mutation To Identify Genetic Pathways Of Exfoliation Syndrome And Circadian Intraocular Pressure

Purpose: Exfoliation syndrome (XFS) is a common age-related disorder characterized by the pathological accumulations of fibrillar exfoliative material in the anterior chamber of the eye. Patients with XFS can go on to develop exfoliative glaucoma; potentially as a result of an accumulation of exfoliative material at the drainage structures of the eye. This can lead to abnormal elevated regulation of intraocular pressure (IOP). Human eyes with XFS exhibit a striking pattern of Marcel-like iris transillumination defects. That pattern is recapitulated in mice containing the Lystbg-J mutation. Others have identified a small number of proteins capable of interacting with the LYST WD40 motif – one of these being CSNK2B. Testing CSNK2B, previous GST-pulldown experiments confirmed that wild-type LYST can bind to CSNK2B whereas LYSTbg-J can not. This result suggests that LYST may play a role in regulating activity or localization of CSNK2B

Methods: Biochemical assays were used to test whether CSNK2B substrates exhibit functional deficits in the presence of the Lystbg-J mutation. A rebound tonometer was used to measure intraocular pressure in wildtype and mice carrying the Lystbg-J mutation.

Results: Intraocular pressure measurements showed that C57BL/6J mice have a biphasic IOP pattern in which IOP was low during the light phase (13.3±2.4 mmHg) and high during the dark phase (15.1±1.9 mmHg). In contrast, mice with the bg-J mutation showed a constant intraocular pressure during the light cycle (12.7±2.5mmHg) with no significant rise in IOP during the dark cycle (12.4±1.8 mmHg). Experiments with two IOP reducing pharmacological drugs indicated that dysfunction of circadian IOP in B6-Lystbg-J mice is dependent on aqueous humor production.

Conclusion: Combined, these results implicate CSNK2B in the pathogenesis of XFS and a genetic pathway impacting circadian IOP regulation. Deciphering the pathogenesis of XFS would therefore be therapeutically beneficial and could lead to better treatment and management of the disease.


Posted on July 6, 2012, in Student Seminar. Bookmark the permalink. Leave a comment.

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