Our lab is interested in the process of eggshell development and its influence on early embryonic development. It has been observed that defects in eggshell development always result in embryonic lethality. It thus remains unclear whether the eggshell provides solely a structural support for the developing embryo or if it also plays a signaling role necessary for early development. It is known that proteins important for eggshell synthesis are carefully regulated and degraded during early development. In an attempt to better understand the role of the eggshell, its synthesis, and what maternal and paternal factors influence its function, we are studying a number of embryonic lethal mutants that have been reported to have eggshell defects. Genetic screens carried out in the early 1980s identified a large collection of interesting mutants, the majority of which were not further studied nor molecularly cloned. With the advent of whole genome sequencing, it is now possible in a very short time (and for very little research funds) to molecularly identify the mutations responsible for these interesting phenotypes. We are currently characterizing all 20 of these mutants in greater detail. For the whole genome sequencing, we are first out-crossing the strains one time to an Hawaiian C. elegans strain and re-isolating our embryonic lethal mutant. Those animals are then subjected to whole genome sequencing. The genomic regions free of Hawaiian SNPs are then identified as the regions bearing our mutation of interest. We then will RNAi candidate genes in these regions to identify the responsible gene. Those mutants with interesting phenotypes will be further characterized. It also remains possible that we may purse specific mutants because of the gene that is disrupted, with a specific focus on genes with human orthologs.
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|Richie, Christopher T; Bembenek, Joshua N; Chestnut, Barry et al. (2011) Protein phosphatase 5 is a negative regulator of separase function during cortical granule exocytosis in C. elegans. J Cell Sci 124:2903-13|
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|Golden, Andy; Liu, Jun; Cohen-Fix, Orna (2009) Inactivation of the C. elegans lipin homolog leads to ER disorganization and to defects in the breakdown and reassembly of the nuclear envelope. J Cell Sci 122:1970-8|
|Moore, Akilah; Golden, Andy (2009) Hypothesis: Bifunctional mitochondrial proteins have centrosomal functions. Environ Mol Mutagen 50:637-48|