Placental and breastmilk microRNAs in relation to early-life growth and metabolism

胎盘和母乳 microRNA 与生命早期生长和代谢的关系

• 批准号: 10191784
• 负责人: Elizabeth Marie Kennedy Goehring
• 金额: $ 13.1万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-09 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10191784
• 关键词: 3' Untranslated Regions; Address; Advisory Committees; Affect; Automobile Driving; Base Pairing; Bioinformatics; Biological Markers; Biology; Birth; Body mass index; Breast Feeding; Breastfed infant; Cardiovascular Diseases; Child; Child Health; Childhood; Code; Cohort Studies; DNA; DNA Methylation; Data; Development; Disease; Educational Status; Epidemiologic Methods; Epidemiologist; Epidemiology; Epigenetic Process; Extracellular Matrix; Faculty; Fetal Growth; Future; Gene Expression; Genes; Genetic; Genetic Research; Genetic Transcription; Genomics; Genotype; Goals; Growth; Health; Home; Human Genetics; Human Milk; Infant; Intestines; Knowledge; Life; Measures; Mediating; Mediator of activation protein; Mentors; Mentorship; Messenger RNA; Metabolic; Metabolic Diseases; Metabolism; Methods; MicroRNAs; Molecular; Molecular Epidemiology; National Institute of Child Health and Human Development; New Hampshire; Obesity; Outcome; Pattern; Phase; Placenta; Placental Biology; Population; Population Study; Positioning Attribute; Pregnancy; Proteins; Public Health Schools; Quantitative Trait Loci; Recommendation; Regulator Genes; Research; Research Design; Research Personnel; Research Project Grants; Research Support; Research Training; Resources; Rhode Island; Role; Secure; Stimulus; Testing; Tissues; Training; Transcript; Universities; Untranslated RNA; Variant; Work; base; career; cohort; disorder prevention; early childhood; early life exposure; empowered; epidemiology study; experience; extracellular; follow-up; genetic variant; genome-wide; gestational weight gain; high risk; improved; insight; interest; multiple omics; next generation; nutrition; obese mothers; obesity in children; obesity risk; offspring; population based; prepregnancy; research study; response; skills; tenure track; transcriptome; transcriptomics

Project Summary The work outlined in this proposal is meant to provide the training and skills necessary to begin my independent academic career as a molecular epidemiologist capable of securing a tenure-track faculty position and my own research support. My doctoral research focused on the mechanistic relationship of DNA methylation and gene transcription, which paved the way for the analysis and interpretation of more complicated population studies of the molecular mechanisms that underlie gestational exposures. My experience has led to my primary research interest in how early-life exposures influence children's health. I will accomplish my goals through training, mentorship and a rigorous research project that integrates genetic, epigenetic and transcriptomic measures to assess the role of placenta- and breastmilk-mediated exposures in relation to early-life growth and metabolism. Through my research and training plan, I will gain expertise in epidemiologic methods and study design; childhood growth, nutrition and obesity; and microRNA biology. I will receive personalized training from my co-mentors, Dr. Carmen Marsit, an expert in molecular epidemiology, and Dr. Usha Ramakrishnan, an expert in children's growth and nutrition. I will receive additional guidance from a transdisciplinary advisory committee composed of Drs. Margaret Karagas, Michael Epstein, and Scott Langevin. This team has expertise in integrative genomics, bioinformatics, statistical genetics, early-life epidemiology and microRNA biology. Emory University is home to Rollins School of Public Health, ranked 5th in the US, as well as to world leaders in epidemiology and human genetics research. The formal training and expert guidance I will receive here will enable me to achieve my long-term career goal of becoming an independent, early-life molecular epidemiologist capable of securing a tenure-track faculty position and my own research support. The research proposed here will address the following gaps in knowledge: 1) the role of placental microRNAs in early-childhood growth and metabolism; 2) the genetic and epigenetic dynamics that underlie microRNA expression in placenta; and 3) the role of placental and extracellular breastmilk microRNAs as mediators of maternal metabolic status influence on early childhood metabolic status. My research will provide insight into the contribution of gestational and early-life exposures in the development of early growth and metabolic status. More broadly, the knowledge gained through this research study has the potential to contribute to microRNA biology, placental biology, obesity and to the Developmental Origins of Health and Disease (DOHaD). Finally, my proposed training and research will prepare me for an independent research career, in which I utilize cutting-edge `omics methods in population-studies to assess the molecular mechanisms that underlie children's health and develop biomarkers that inform recommendations for disease prevention.

项目摘要 该提案中概述的工作旨在提供开始我的培训和技能 独立的学术职业作为分子流行病学家，能够确保终身教师职位 和我自己的研究支持。我的博士研究重点是DNA的机械关系 甲基化和基因转录，为分析和解释铺平了道路 对妊娠暴露的分子机制的复杂种群研究。我的 经验使我对早期生活如何影响儿童健康的主要研究兴趣。我会 通过培训，指导和严格的研究项目来实现我的目标，该项目整合了遗传， 表观遗传和转录组措施评估胎盘和母乳介导的暴露在 与早期生命的生长和新陈代谢有关。 通过我的研究和培训计划，我将获得流行病学方法的专业知识并研究 设计;儿童时期的生长，营养和肥胖；和microRNA生物学。我将从 我的副官员Carmen Marsit博士是分子流行病学专家，以及Usha Ramakrishnan博士， 儿童成长和营养专家。我将获得跨学科咨询的其他指导 由Drs组成的委员会。玛格丽特·卡拉加斯，迈克尔·爱泼斯坦和斯科特·兰格文。这个团队有专业知识 在综合基因组学，生物信息学，统计遗传学，早期流行病学和microRNA生物学中。 埃默里大学（Emory University）是罗林斯公共卫生学院的所在地，在美国排名第五，以及世界领导人 流行病学和人类遗传学研究。我将在这里获得的正式培训和专家指导将 使我能够实现成为独立的早期分子的长期职业目标 流行病学家能够确保终身教师职位和我自己的研究支持。 这里提出的研究将解决知识的以下差距：1）胎盘的作用 早期生长和代谢中的microRNA； 2）基础的遗传和表观遗传动力学 胎盘中的microRNA表达； 3）胎盘和细胞外母乳的角色作为 孕产妇代谢地位对幼儿代谢状况的影响。我的研究将提供 深入了解妊娠和早期生活在早期增长发展和早期生活的贡献 代谢状态。更广泛地，通过这项研究获得的知识有可能 有助于microRNA生物学，胎盘生物学，肥胖以及健康的发展起源 疾病（Dohad）。最后，我提出的培训和研究将使我为一项独立研究做好准备 我利用尖端的“人口研究中的法律方法”来评估分子 基于儿童健康和发展生物标志物的机制，以告知疾病建议 预防。