Determination of the Role of Protein Arginine Methylation in HMGA1a Function

通过添加特定的官能团来修饰细胞蛋白质对于调节细胞的生物功能是很重要的。这个过程被称为翻译后修饰，可以涉及到各种化学基团的添加，并可以控制蛋白质在各种细胞器中的位置，或者可以增强蛋白质与其细胞伴侣的相互作用。萨姆特博士的研究将研究高迁移率组A1a(HMGA1a)的翻译后修饰，HMGA1a是一种直接参与调控基因表达的蛋白质。这种蛋白质通常在其高度保守的区域被化学修饰，尽管其重要性尚未被评估。HMGA1a修饰位点的定点突变将与生化分析相结合，以确定它们在基因转录激活中的重要性。这些初步数据将为未来鉴定参与HMGA1a修饰的精氨酸甲基转移酶奠定基础，并为翻译后修饰在转录调控中的重要性提供见解。这项提案中概述的研究将促进目前对基因表达调控的了解，并将使我能够就细胞调节生物过程的机制得出重要结论。萨姆特博士的跨学科研究兴趣结合了分子生物学和生物化学的技术，将为本科生提供极好的培训机会。她的目标是通过使用生物系统教授普通化学主题，并在协作学习环境中提供分子生物学和生物化学的研究经验，提高化学和生物科学专业学生的留存率，培养未被充分代表的群体对生物科学的兴趣，这将加强学生对研究生培训和生物学职业的准备。课程的修改将培养本科生追求独立研究机会的兴趣。研究参与者将设计、执行、分析并从实验中得出结论。这种体验最终将有机会向科学受众介绍地方和国家的科学项目。研究环境对来自贫困背景的学生特别有吸引力，因为它使用了一种合作模式，即学生在研究团队中工作，以减少竞争和孤立。预计该项目将支持非政府组织的专业发展，同时促进少数群体和妇女对科学的兴趣。

Modifying cellular proteins by the addition of specific functional groups is important in regulating the biological functions of cells. This process, called posttranslational modification, can involve the addition of a variety of chemical groups and can govern a protein's location within various cellular organelles or can enhance a protein's interaction with its cellular partner. Dr. Sumter's research will study posttranslational modification of High Mobility Group A1a (HMGA1a), a protein directly involved in regulating gene expression. This protein typically is chemically modified in its highly conserved regions although the significance has not been evaluated. Site-directed mutagenesis of sites of modification of HMGA1a combined with biochemical assays will be used to ascertain their importance in transcriptional activation of genes. These preliminary data will lay the foundation for future identification of the arginine methyltransferase involved in HMGA1a modification and provide insights into the importance of posttranslational modifications in regulating transcription. The research outlined in this proposal will advance current knowledge of regulation of gene expression and will allow important conclusions to me made about mechanisms employed by cells to regulate biological processes. Dr. Sumter's interdisciplinary research interests combine techniques in molecular biology and biochemistry and will provide excellent training opportunities for undergraduates students. She aims to foster the interest of underrepresented groups in biological sciences by increasing retention of chemistry and biology science majors by using biological systems to teach topics in general chemistry and providing research experiences in molecular biology and biochemistry in a collaborative learning environment that will enhance student preparation for postgraduate training and careers in biology. Modifications in courses will foster the interests of undergraduates in pursuing independent research opportunities. Research participants will design, carry out, analyze, and draw conclusions from experiments. The experience will culminate with opportunities to present scientific projects locally and nationally to scientific audiences. The research environment is exceptionally attractive for students from underserved backgrounds because it uses a collaborative model in which students work in research teams to diminish competition and isolation. It is anticipated that this project will support the PI's professional development while also fostering the interests of minorities and women in science.