Identification of regulators in the vertebrate egg-to-embryo transition
脊椎动物卵到胚胎转变过程中调节因子的鉴定
基本信息
- 批准号:10371345
- 负责人:
- 金额:$ 9.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-12 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAdvisory CommitteesAnimalsAwardCandidate Disease GeneCell physiologyCellular biologyClinicComplexCongenital AbnormalityDNADefectDepositionDevelopmentEmbryoEmbryonic DevelopmentEventFemaleFertilityGene DuplicationGenesGeneticGenomeGermGerm CellsGoalsHumanImageImpairmentInfertilityMentorsMentorshipMicrotubulesModelingMolecularMorphologyMutationNatureNuclearNuclear EnvelopeOocytesOrthologous GenePathway interactionsPatternPhasePhenotypePregnancyProcessRNAResearchResearch PersonnelRoleSpontaneous abortionTechniquesTrainingVertebratesZebrafishalpha Karyopherinsborealincritical periodearly pregnancy lossegggene productgenetic approachimplantationinsightmutantnoveloffspringprogramsskillsskills trainingsurvivintoolwhole genome
项目摘要
Project Summary
Across vertebrates, early development, prior to zygotic genome activation, is dependent on maternally supplied
gene products. These products will initiate molecular pathways that are necessary for the embryonic
developmental programing. Mutations that disrupt the function or stability of these maternal products can be
lethal to the developing embryo. Females who carry these impaired maternal-effect genes do not display an
overt phenotype, but their offspring will undergo abnormal development that is independent of their genetics.
Despite the importance of maternal-effect genes in early development, we have only determined the function of
a small subset of maternal-effect genes via genetic approaches. In humans, defects in maternally expressed
genes are expected to result in failed implantation or early pregnancy loss. The Mayo Clinic estimates that ten
to twenty percent of known pregnancies are miscarried, but this percentage is likely significantly higher because
early miscarriages can go undetected. This proposal aims to address the role of maternally expressed genes
during the egg to embryo transition. Specifically, in Aim 1 (K99), I will perform live subcellular imaging to
characterize the role of a maternally expressed chromosomal passenger complex in regulating the dynamic
nature of microtubule-dependent germplasm aggregation. In Aim 2 (K99), I will be exploring the role of a
maternally expressed Importin-α, Kpna7 in regulating nuclear envelope reassembly during the egg-to-embryo
transition. During my R00 years, I will use a large scale maternal-crispant screen to identify novel regulators of
the egg-to-embryo transition. Preliminary studies have suggested that this is an efficient way to determine the
role of maternally expressed genes in development. By combining this maternal crispant screen with live
subcellular imaging of the dynamic processes that are required for early development, I will start understanding
the role of newly identified maternal effect genes in early embryo. My K99 training will be guided by exceptional
mentors, Dr. Francisco Pelegri and Dr. William Bement, and an advisory committee, all of whom will provide
support and mentorship allowing me to transition into independence. The combination of my established genetic
editing skill and the training in live subcellular imaging with Dr. Bement will give me the unique skill set that is
required to research the role of the maternally expressed genes in the egg-to-embryo transition. The K99/R00
award will allow me to become an independent investigator in the role of maternal products during development
and will provide understanding into the genetics of infertility and early pregnancy loss.
项目摘要
在脊椎动物中,合子基因组激活之前的早期发育依赖于母体提供的
基因产物这些产物将启动胚胎发育所必需的分子途径,
发展规划破坏这些母体产物功能或稳定性的突变可能会
对发育中的胚胎致命携带这些受损的母性效应基因的女性不会表现出
显性表型,但其后代将经历不依赖于其遗传的异常发育。
尽管母体效应基因在早期发育中很重要,但我们只确定了
一小部分母源基因。在人类中,母性表达的缺陷
预期基因会导致着床失败或早孕丢失。马约诊所估计,
已知的怀孕中有20%是流产的,但这一比例可能要高得多,
早期流产可能不会被发现。这项建议旨在解决母系表达基因的作用
从卵子到胚胎的转变。具体来说,在目标1(K99)中,我将进行活的亚细胞成像,
描述母体表达的染色体乘客复合物在调节动态
微管依赖的种质聚集的性质。在目标2(K99)中,我将探讨
母源性表达的Importin-α、Kpna 7在卵胚发育过程中对核膜重组的调控
过渡在我的R 00年里,我将使用一个大规模的母脆屏幕,以确定新的监管机构,
卵子到胚胎的转变初步研究表明,这是一种有效的方法来确定
母系表达基因在发育中的作用。通过将这种母亲般清脆的屏幕与现场
早期发育所需的动态过程的亚细胞成像,我将开始了解
新发现的母体效应基因在早期胚胎中的作用。我的K99培训将由卓越的
导师,弗朗西斯科Pelegri博士和威廉Bement博士,以及一个咨询委员会,他们都将提供
支持和指导使我能够过渡到独立。我的基因组合
编辑技能和Bement博士在活亚细胞成像方面的培训将给我带来独特的技能,
需要研究母源表达基因在卵到胚胎转变中的作用。K99/R00
该奖项将使我成为一个独立的调查员在母体产品的作用,在发展过程中
并将提供对不孕症和早孕丢失的遗传学的理解。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Cara Moravec其他文献
Cara Moravec的其他文献
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{{ truncateString('Cara Moravec', 18)}}的其他基金
Identification of regulators in the vertebrate egg-to-embryo transition
脊椎动物卵到胚胎转变过程中调节因子的鉴定
- 批准号:
10663791 - 财政年份:2022
- 资助金额:
$ 9.1万 - 项目类别:
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