Spatially Regulated Translation of the Maternal xCR1 mRNA During Xenopus Development

智力优势：具有脊椎（脊椎动物）的生物体的胚胎最初基本上是细胞球。为了形成特定的成人组织和结构，胚胎细胞必须接受特定的指令，在特定的时间和地点合成特定的分子。在许多情况下，这些重要的指令本身就是分子。它们被称为信使rna (mrna)，它们将DNA编码的信息从细胞核传递到细胞质，以合成蛋白质——细胞的主力分子。该项目的目标是阐明调节这一过程的基本机制。这项研究将在非洲爪蟾（Xenopus）的胚胎中进行，这是一种方便的模式生物，研究重点是一种mRNA分子，它指导一种重要蛋白质Cripto-1的合成。Cripto-1蛋白及其合成步骤对所有脊椎动物的胚胎都同样重要。在之前的工作中，研究小组发现，从mRNA合成Cripto-1蛋白受到高度调控，只发生在一组特定的胚胎细胞中。该项目旨在从分子角度阐明这种调节的机制。关键的初步结果表明，这种调节涉及到一种名为Bicaudal-C （bical - c）的蛋白质与Cripto-1 mRNA的特定区域的结合，确保只在正确的时间和适当的细胞中合成Cripto-1蛋白。该项目将确定Bic-C对Cripto-1 mRNA特异性识别的分子决定因素，以及这种结合如何刺激Cripto-1蛋白的合成。更广泛的影响：该项目解决了一个广泛感兴趣的基础研究问题，将加强学生在各级（本科生、研究生和博士后）的科学研究的参与和训练。PI将亲自监督学生，并确保他们在研究的各个方面从事智力上有意义和技术上严谨的方式。最重要的教育目标是促进学生在各个阶段的智力发展，并确保他们朝着科学独立的方向稳步前进。对于参与的本科生，目标是在毕业前完成一篇高级荣誉论文。对研究生来说，目标是发表大量论文，为从事研究工作做好准备。威斯康星大学麦迪逊分校的协作性质和强大的科学社区，代表了广泛的研究方法和风格，将进一步加强学生的教育。PI将通过威斯康辛大学的项目积极招收代表性不足的少数民族学生。此外，PI在培养女性博士生和博士后科学家方面有着良好的记录，并将继续鼓励女性参与研究。PI将继续积极参与公共科学教育，举办研讨会并向几个非学术团体提供信息，包括“一角硬币游行”的地方分会。此外，PI还将在当地小学开展推广探究性科学学习方法的活动。PI将领导包括观察和分析活青蛙胚胎发育的活动。通过测量参与活动的教师和学生对科学的态度和对科学的学习的变化来评价外展活动的有效性。

Intellectual Merit: The embryos of organisms with backbones (vertebrates) begin life essentially as balls of cells. To form specific adult tissues and structures, the cells of the embryos must receive specific instructions that direct the synthesis of particular molecules at particular times and places. In many cases, these important instructions are themselves molecules. They are called messenger RNAs (mRNAs) and they transmit the information encoded in DNA from a cell's nucleus to its cytoplasm for synthesis of proteins, the cell's workhorse molecules. The goal of this project is to elucidate the fundamental mechanisms for regulating this process. The studies will be carried out in the embryos of the frog, Xenopus, a convenient model organism, focusing on an mRNA molecule which directs the synthesis of an important protein called Cripto-1. The Cripto-1 protein and the steps leading to its synthesis are equally important for embryos of all vertebrates. In previous work, the research team discovered that the synthesis of the Cripto-1 protein from its mRNA is highly regulated and occurs only in a specific set of embryonic cells. The project is designed to elucidate the mechanisms of this regulation in molecular terms. Critical preliminary results showed that this regulation involves binding of a protein called Bicaudal-C (Bic-C) to specific regions of the Cripto-1 mRNA, ensuring that the Cripto-1 protein is synthesized only at the correct time and in the appropriate cells. The project will define the molecular determinants for specific recognition of Cripto-1 mRNA by Bic-C and how this binding stimulates synthesis of Cripto-1 protein.Broader Impact: This project addresses a fundamental research question of wide interest that will enhance student participation and training in scientific research at all levels (undergraduate, graduate, and post-doctoral). The PI will personally supervise students and ensure that they engage in intellectually meaningful and technically rigorous ways with all aspects of the research. The overriding educational goal is to foster the intellectual growth of students at all stages and ensure steady progress toward scientific independence. For participating undergraduate students, the goal is completing a Senior Honors Thesis by graduation. For graduate students, the goal is strong publications and preparation for careers in research. The collaborative nature of the work and the strong scientific community at UW Madison, representing a wide range of approaches and styles of research, will further enhance student education. The PI will actively recruit students that are members of under-represented minorities through University of Wisconsin programs. Furthermore, the PI has a strong record of training female Ph.D students and postdoctoral scientists and will continue to encourage the participation of women in the research. The PI will continue to be actively involved in public science education by giving seminars and providing information to several non-academic groups including local chapters of the March of Dimes. In addition, the PI will perform outreach activities to local elementary schools that promote inquiry-based approaches to science learning. The PI will lead activities involving observation and analysis of the development of live frog embryos. The effectiveness of outreach activities will be evaluated by measuring the changes in attitude toward science and learning about science among participating teachers and students.