RIG/CAA: The Role of Alternative Splicing of the Fibroblast Growth Factor Receptor in Cardiac Development by the Heterogeneous Nuclear Ribonucleoprotein A1

RIG/CAA：异质核核糖核蛋白 A1 选择性剪接成纤维细胞生长因子受体在心脏发育中的作用

• 批准号: 0542286
• 负责人: Natalie Bronstein
• 金额: $ 17.46万
• 依托单位: MERCY UNIVERSITY
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0542286&HistoricalAwards=false
• 关键词: RIG; CAA; Role; Alternative; Splicing

Research Initiation Grant (RIG): The Role of Alternative Splicing of the Fibroblast Growth Factor Receptor in Cardiac Development by the Heterogeneous Nuclear Ribonucleoprotein A1Intellectual Merit: Alternative splicing is the mechanism by which one gene can code for many protein variants (isoforms). The genome projects of higher organisms have revealed that alternative splicing is an important mechanism underlying protein isoform and diversity. Dr. Bronstein seeks to gain a greater understanding of the role played by alternative splicing in a vertebrate heart developmental model. More specifically, this project will investigate regulatory mechanisms involved in the alternative splicing process that underlies isoform diversity of Fibroblast Growth Factor Receptors (FGFRs) during early chicken cardiogenesis. FGFRs are important in regulating the differentiation of embryonic tissue either into epithelia or mesenchyme depending upon which FGFR isoform is expressed. Dr. Bronstein is interested in the role of the heterogeneous nuclearribonucleoprotein A1 (hnRNP A1 or A1) and its interactions in determining the splice choice selection of FGFR isoforms. A1, a trans-acting splicing silencer and shuttle protein found in the core protein complex of the spliceosome, is expressed in many organ systems in a cell-specific manner. In the case of heart development, she hypothesizes that A1 may be involved in the alternative splicing of FGFR2. Thus, she proposes to study the spatial and temporal coordination of A1 expression as well as its post-transcriptional control. She hypothesize that A1 determines splice choice selection of the high affinity ligand-binding IIIc isoform of FGFR2 and is involved in cardiogenesis. By developing a system for modifying FGFR signaling via A1 manipulation, she will gaina greater understanding of the role of alternative splicing in heart development.Broader Impacts: This project will both allow the PI to develop as an independentresearcher and enable underrepresented undergraduate students at Mercy College the opportunity to participate in original and potentially publishable, hypothesis-driven research. This work will be performed in a newly equipped research science laboratory at the new Mercy College campus in the Bronx, NY. Mercy College, a federally designated Hispanic Serving Institution, serves a diverse population of traditional and non-traditional students, including those from academically and educational disadvantaged backgrounds. As a developmental biologist with an interest in conducting research in molecular genetics of vertebrate development, the PI would bring a broad research and training experience to our diverse cohort of undergraduate students, thus exposing them to advanced molecular biology, biochemical and analytical techniques. As a mechanism for integrating research and education, we also intend to introduce the assays she develops into her upper level classes so that other students not actively engaged in our research project will be exposed to these state-of-the-art methods. Thus, this project will broaden the participation of individuals from underrepresented groups in the areas of the biological sciences supported by the NSF Directorate for Biological Sciences thereby enabling her students to pursue their goals of obtaining advanced degrees and giving the opportunity to PI in becoming an independent researcher.

研究启动拨款(RIG)：成纤维细胞生长因子受体的选择性剪接在心脏发育中的作用异质核糖核蛋白A1智力优点：选择性剪接是一种机制，通过这种机制，一个基因可以编码许多蛋白质变体(异构体)。高等生物的基因组计划揭示了选择性剪接是蛋白质异构体和多样性的重要机制。布朗斯坦博士试图更深入地了解选择性剪接在脊椎动物心脏发育模型中所起的作用。更具体地说，该项目将研究鸡心脏发生早期成纤维细胞生长因子受体(FGFRs)异构体多样性所涉及的选择性剪接过程中的调控机制。FGFRs在调节胚胎组织分化为上皮或间充质中起重要作用，这取决于FGFR亚型的表达。Bronstein博士感兴趣的是异质核核糖核蛋白A1(hnRNP A1或A1)及其相互作用在决定FGFR亚型的剪接选择选择中的作用。A1是一种反式剪接沉默蛋白和穿梭蛋白，存在于剪接体的核心蛋白复合体中，在许多器官系统中以细胞特异性的方式表达。在心脏发育的情况下，她假设A1可能参与了FGFR2的选择性剪接。因此，她建议研究A1表达的时空协调及其转录后控制。她假设A1决定了FGFR2高亲和力配体结合IIIc亚型的剪接选择，并参与心脏发生。通过开发一个通过A1操作修改FGFR信号的系统，她将更好地理解替代剪接在心脏发育中的作用。广泛的影响：这个项目将使PI发展成为一个独立的研究人员，并使Mercy College的未被充分代表的本科生有机会参与原创的、可能发表的、假设驱动的研究。这项工作将在纽约州布朗克斯区默西学院新校区的一个新配备的研究科学实验室进行。仁慈学院是联邦指定的西班牙裔服务机构，为不同群体的传统和非传统学生提供服务，包括那些来自学业和教育背景不利的学生。作为一名对脊椎动物发育的分子遗传学研究感兴趣的发育生物学家，PI将为我们不同的本科生带来广泛的研究和培训经验，从而使他们接触先进的分子生物学、生化和分析技术。作为一种整合研究和教育的机制，我们还打算将她开发的化验方法引入她的高年级班级，以便其他不积极参与我们研究项目的学生能够接触到这些最先进的方法。因此，该项目将扩大由国家科学基金会生物科学局支持的生物科学领域中来自代表性不足群体的个人的参与，从而使她的学生能够追求他们获得高级学位的目标，并使PI有机会成为一名独立研究人员。