Smolikove ABSTRACT MCB-1121150 Intellectual merit: Meiosis is a fundamental biological process required for sexual reproduction, and is a major contributor to genetic variability. A crucial step in meiosis is the segregation of maternal and paternal (homologous) chromosomes during the first meiotic division. The accurate execution of this step requires the exchange of genetic information between homologous chromosomes leading to crossover formation. The synaptonemal complex (SC) is a key structure, placed in the center of events unfolding in meiosis. The SC is assembled between each pair of homologous chromosomes to ensure the formation of all obligatory crossover events, after which the SC is disassembled in a regulated fashion. In the absence of the SC, chromosomes missegregate in the first meiotic division, often leading to embryonic lethality. The understanding of SC assembly has greatly advanced in the past years, but little progress has been made in understanding the mechanisms of SC disassembly. Dr.Smolikove's research is aimed at elucidating the mechanisms of SC disassembly. To do so, she takes advantage of the numerous genetic, cytological, and molecular tools available in the model organism Caenorhabditis elegans. She has identified a gene which is specifically required for SC disassembly but which does not participate in early meiotic events such as crossover formation or SC assembly. Through molecular and cytological characterization of two alleles of the mutated gene, along with depletion of its mRNA via RNAi, she dissects the molecular pathways required for SC disassembly. Furthermore, performing genetic screens using her mutants, she is helping to reveal the pathway regulating SC disassembly. Over all, this research will lead to a better understanding of SC disassembly and its role in proper meiotic chromosome segregation.
Broader Impacts: This project will provide research opportunities for undergraduates and graduate students from the University of Iowa and from local colleges, along with Ph.D. thesis projects for graduate students. The project will contribute to graduate course material and curriculum development, including a genetics lab course that features experiments using C. elegans and focusing on meiosis, It will serve as an opportunity to introduce basic genetic concepts in an appropriate model organism with a powerful genetic system. Students will be trained in cutting-edge research techniques.