Promoting Diversity via Single-cell Metabolomics and Proteomics: The Missing Link to Understanding Vertebrate Embryonic Patterning

摘要 该项目的目标是通过培养博士学位来增强生物医学研究队伍的多样性。 来自代表性不足背景的研究生，使他们能够进行原创研究和职业生涯 化学和生物前沿的发展。学生将学习高等生物分析化学 和脊椎动物胚胎学，同时阐明了细胞命运变化的作用机制 Nemes研究实验室最近发现的一种叫做代谢物的分子。理解 胚胎发生需要了解受精卵分化为三种类型时产生的所有分子。 胚胎的初级生殖层。四十年来创新的胚胎操作，基因测试 一次只有一个基因发挥功能，最近，下一代测序发现了多个转录本 和丰富的蛋白质，对脊椎动物胚胎的模式是必不可少的。然而，很少有 已知称为代谢物的小分子对胚层的形成和 胚胎的长期发育和功能。拟议的培训-研究计划填补了这一点 通过赋予博士生进行创新的能力来实现技术和生物学方面的知识差距 在化学-生物界面上进行研究。学生将发展生物分析化学方面的技能， 毛细管电泳联用超灵敏电喷雾电离定量代谢组学 质谱仪能够表征细胞和组织的代谢状态。此外， 学生还将发展所需的生物医学-生物学技能，以学习发展和认知 细胞命运决定的含义，包括经典的胚胎学操作，细胞命运追踪，非洲爪哇 莱维斯生物学和行为分析。这种跨学科方法的结果将有助于阐明 代谢组在建立这些重要的前体细胞和组织中的作用。因为这些 分子过程在脊椎动物中是高度保守的，从非洲爪哇收集的数据可能会 与人类结构性出生缺陷有很高的相关性。新的生化信息将在 在几个关键发育时间点的单个胚胎细胞及其后代(细胞谱系)也将 推进涉及细胞分化(例如，干细胞)和发育起源的其他研究领域 成人疾病。该项目将提供身临其境的跨学科培训-研究体验，以实现 学生追求独立的职业生涯，同时使生物医学研究队伍多样化。 Nemes-抽象-1|1

Abstract The goal of this project is to enhance the diversity of the biomedical research workforce by training a PhD Graduate Student from underrepresented backgrounds to enable their original research and career development at the frontiers of chemistry and biology. The student will learn advanced bioanalytical chemistry and vertebrate embryology while elucidating the mechanism of action underlying cell fate changes by small molecules called metabolites, which the Nemes Research Laboratory has recently discovered. Understanding embryogenesis requires knowledge of all the molecules produced as the zygote differentiates into the three primary germ layers of the embryo. Four decades of innovative embryological manipulations, testing of gene functions one gene at a time, and recently, Next-Generation Sequencing have identified multiple transcripts and abundant proteins that are essential to the patterning of the vertebrate embryo. However, very little is known about the contribution of small molecules called metabolites to the formation of the germ layers and the long-term development and functioning of the embryo. The proposed training–research program fills this knowledge gap in technology and biology by empowering the PhD Graduate Student to conduct original research at the chemistry-biology interface. The student will develop skills in bioanalytical chemistry, specifically quantitative metabolomics by capillary electrophoresis and ultrasensitive electrospray ionization mass spectrometry to enable the characterization of the metabolomic states of cells and tissues. Further, the student will also develop the required biomedical–biological skills to study the developmental and cognitive implications of cell fate decisions, including classical embryological manipulations, cell fate tracking, Xenopus laevis biology, and behavioral assays. The outcomes of this interdisciplinary approach will help illuminate the role of the metabolome for the establishment of these important precursor cells and tissues. Because these molecular processes are highly conserved across vertebrates, the data collected from Xenopus are likely to have high relevance to human structural birth defects. The new biochemical information that will be obtained in individual embryonic cells and their progeny (cell lineage) at several critical developmental time points will also advance other research fields that involve cell differentiation (e.g., of stem cells) and the developmental origins of adult disease. This project will provide immersive cross-disciplinary training–research experience to enable the student to pursue an independent career while diversifying the biomedical research workforce. Nemes-Abstract-1|1