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Assistant Professor of Biology
Office: 308 BBIowa City, IA 52242
Email: firstname.lastname@example.orgWeb: More About Dr. Smolikove - Related Websites and Resources
BS, Biology, Tel Aviv UniversityMS, Biology, Tel Aviv UniversityPhD, Molecular Microbiology, Tel Aviv University
Interdisciplinary Graduate Program in GeneticsInterdisciplinary Graduate Program in Molecular and Cellular BiologyInterdisciplinary Graduate Program in Neuroscience
We are interested in understanding the crucial steps that lead to faithful chromosome segregation during meiosis. Meiosis is a specialized cell division that results in the formation of gametes (as sperm and eggs). Unlike mitosis, which concludes in the formation of identical daughters to the progenitor cell, meiosis results in the reduction of the number of chromosomes by half. Therefore, the meiotic division sets the stage for the mixing and matching of genetic information to create novel genetic combinations during sexual reproduction. Errors in the meiotic divisions may result in the formation of aneuploid gametes (gametes with an extra or missing chromosome). Understanding the origin of aneuploidy is crucial since it is the leading known cause for miscarriages and the leading genetic cause for developmental disabilities and mental retardation.
Accurate chromosome segregation during the first meiotic division relies on maintaining the attachments between each pair of homologous chromosomes prior to the onset of the first meiotic division. This attachment is mediated via sister chromatid cohesion and crossover formation. The formation of the synaptonemal complex (SC) is a crucial event unfolding during meiotic prophase I (Figure 1), which allows the stable association of homologous chromosomes and is required for the formation of all obligatory crossover events. It is well established that defects in SC formation lead to aneuploidy, pointing to the central role the SC plays in chromosome segregation.
Given that meiosis is a conserved and fundamental process, it is surprising that many of its features remain poorly understood. Among these are the mechanisms of SC assembly and disassembly. In our lab we investigate these topics, as well as other aspects of meiotic prophase I through the study of C. elegans, an ideal genetic model system. Meiotic prophase nuclei are the majority of nuclei composing the germline of the worm (Figure 2a). These nuclei are arranged in temporal-spatial pattern (Figure 2b), therefore SC morphogenesis can be studied by high resolution microscopy of C. elegans gonads (Figure 2b-e). Through genetic screens for SC morphogenesis defects, we identify and characterize novel proteins essential for SC function. A pilot screen has already resulted in the identification of several meiotic mutants. One of these mutants exhibits high levels of embryonic lethality, associated with severe defects in SC disassembly. Studies of this unique SC morphogenesis defect will allow us to understand how SC disassembly is regulated and the crucial role it plays in proper chromosome segregation. In addition, through a suppressor/enhancer screen of this mutant, we will identify novel genes affecting chromosome segregation via the regulation of SC disassembly. Altogether our studies will lead to a better understanding of the events leading to accurate chromosome segregation, which is essential for improving human health as well as understanding the fundamental biological process of meiosis.
Date Last Modified: 04/12/2016 -
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