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Cell Cycle Regulation In C. elegans

线虫的细胞周期调控

基本信息

批准号：
8553386
负责人：
Andy Golden
金额：
$ 14.82万
依托单位：
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

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.

我们的实验室对蛋壳发育过程及其对早期胚胎发育的影响感兴趣。据观察，蛋壳发育缺陷总是会导致胚胎死亡。因此，目前尚不清楚蛋壳是否仅为发育中的胚胎提供结构支持，或者它是否也发挥了早期发育所需的信号作用。已知对蛋壳合成重要的蛋白质在早期发育期间受到仔细调节和降解。为了更好地了解蛋壳的作用，它的合成，以及母亲和父亲的因素影响它的功能，我们正在研究一些胚胎致死突变体，据报道有蛋壳缺陷。在20世纪80年代早期进行的遗传筛选鉴定了大量有趣的突变体，其中大多数未被进一步研究或分子克隆。随着全基因组测序技术的出现，现在可以在很短的时间内（而且只需要很少的研究资金）从分子上鉴定出导致这些有趣表型的突变。我们目前正在更详细地描述所有20种突变体。对于全基因组测序，我们首先将菌株与夏威夷C. elegans菌株并重新分离我们的胚胎致死突变体。然后对这些动物进行全基因组测序。然后将没有夏威夷SNP的基因组区域鉴定为携带我们感兴趣的突变的区域。然后我们将RNAi候选基因定位在这些区域，以确定负责基因。具有感兴趣的表型的那些突变体将被进一步表征。我们也有可能因为基因被破坏而寻找特定的突变体，特别关注具有人类直系同源物的基因。