The Role of IME4 and IME2 in Drosophila Gametogenesis

IME4 和 IME2 在果蝇配子发生中的作用

• 批准号: 7448013
• 负责人: CINTIA Fabiana HONGAY
• 金额: $ 9万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7448013
• 关键词: Affect; Animal Model; Award; Cell division; Cells; Commit; Cytological Techniques; Data; Deletion Mutation; Diploidy; Drosophila genus; Drosophila melanogaster; Eukaryota; Eukaryotic Cell; Event; Female; Fertilization; Functional disorder; Gametogenesis; Gene Expression Profile; Genes; Genetic; Genetic Programming; Germ; Germ Cell Cancers; Germ Cells; Goals; Gonadal structure; Haploid Cells; Haploidy; Homologous Gene; Human; In Vitro; Infertility; Laboratories; Learning; Licensing; Malignant Neoplasms; Meiosis; Mentors; Methyltransferase; Mitosis; Mitotic; Molecular Genetics; Mus; Numbers; Oogenesis; Organism; Orthologous Gene; Phase; Phenotype; Phosphotransferases; Population; Proteins; Proteome; Public Health; RNA; RNA Interference; RNA methylation; Rattus; Research; Research Personnel; Research Project Grants; Role; Saccharomyces cerevisiae; Saccharomycetales; Site-Directed Mutagenesis; Spermatogenesis; Stem cells; Training; Yeasts; egg; fly; insight; knock-down; male; mutant; programs; research study; sperm cell; stem; tool

DESCRIPTION (provided by applicant): The long-term goal of my studies is to elucidate the early events in the genetic program conducive to meiotic cell fate determination in metazoans using Drosophila melanogaster-the metazoan model organism in which I will be trained during the mentored phase of this award. I will start my research by investigating IME2 and IME4, two highly conserved genes that have been shown to be required for meiosis in S. cerevisiae. The understandig of the genetic program that determines meiotic cell fate will provide insight into understanding infertility and the consequences of dysfunction of the mitotic:meiotic switch. Both IME2 and IME4 have homologs in mice, rats, and humans. Specific aims: The specific aims of this proposal span both the two-year mentored phase of this award in which I will train in D. melanogaster's husbandry, genetics, molecular genetics and cytological techniques to investigate the role of IME4 and IME2 in meiosis, and the three year independent phase of this award in which I will further pursue my findings and establish myself as an independent investigator: Phase I: Aim 1: To create mutants of ime4 and ime2 in D. melanogaster by classical genetics and RNAi knock-downs and initiate their phenotypic characterization. Aim 2: To study the specific roles of Ime4 and Ime2 in oogenesis and spermatogenesis. Phase II: Aim 3: To investigate the role of Ime4 as an RNA methyltransferase in gametogenesis and identify its targets for this modification. Aim 4: To determine the role of Ime2 as a kinase in gametogenesis and identify its substrates. Relevance to public health: Male and female germ cells commit some of its cells to reduce by half their chromosomal content to become sperm and egg respectively by a specialized cell division called meiosis. The early factors that determine commitment to meiosis are not known. My proposed experiments are aimed at elucidatng the genetic program that makes a germ cell enter meiosis. My findings will provide information to understand infertility and the role of proper function of the mitosis:meiosis switch whose dysfunction has been suspected in some germline cancers.

描述（由申请人提供）：我的研究的长期目标是阐明早期事件的遗传程序有利于减数分裂细胞的命运决定在后生动物使用果蝇的后生动物模式生物，我将在本奖项的指导阶段进行培训。我将从研究IME2和IME4开始我的研究，这两个高度保守的基因已被证明是S减数分裂所必需的。啤酒。对决定减数分裂细胞命运的遗传程序的理解将为理解不育和有丝分裂：减数分裂开关功能障碍的后果提供见解。IME2和IME4在小鼠、大鼠和人类中都有同源物。具体目标：这个建议的具体目标跨越了这个奖项的两年指导阶段，我将在D。本研究将利用黑腹果蝇的饲养学、遗传学、分子遗传学和细胞学技术研究IME4和IME2在减数分裂中的作用，并将在本研究的三年独立研究阶段中进一步研究我的发现，并将自己确立为一名独立研究者：第一阶段：目标1：在D.通过经典遗传学和RNAi敲低来诱导黑腹果蝇的表达，并启动它们的表型表征。目的2：研究Ime4和Ime2在卵子发生和精子发生中的特异性作用。第二阶段：目的3：研究Ime4作为RNA甲基转移酶在配子发生中的作用，并确定其修饰的靶点。目的4：确定Ime2作为一种激酶在配子发生中的作用，并鉴定其底物。与公共卫生的相关性：雄性和雌性生殖细胞通过一种称为减数分裂的特殊细胞分裂，将其一些细胞的染色体含量减少一半，分别成为精子和卵子。决定减数分裂定型的早期因素尚不清楚。我提出的实验旨在阐明使生殖细胞进入减数分裂的遗传程序。我的研究结果将提供信息，以了解不孕症和有丝分裂的作用：减数分裂开关的功能障碍已被怀疑在一些生殖系癌症。