Determination of the Role of Protein Arginine Methylation in HMGA1a Function

通过添加特定的功能基团来修饰细胞蛋白在调节细胞的生物功能方面是重要的。这一过程被称为翻译后修饰，可以包括添加各种化学基团，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细胞伴侣的相互作用。Sumter博士的研究将研究高迁移率组A1a （HMGA1a）的翻译后修饰，这是一种直接参与调节基因表达的蛋白质。这种蛋白质通常在其高度保守的区域进行化学修饰，尽管其意义尚未得到评估。对HMGA1a的修饰位点进行定点诱变，并结合生化分析，以确定其在基因转录激活中的重要性。这些初步数据将为未来确定参与HMGA1a修饰的精氨酸甲基转移酶奠定基础，并为了解翻译后修饰在调节转录中的重要性提供见解。本提案中概述的研究将推进当前对基因表达调控的认识，并将使我对细胞调节生物过程的机制得出重要结论。Sumter博士的跨学科研究兴趣结合了分子生物学和生物化学技术，将为本科生提供良好的培训机会。她的目标是通过使用生物系统来教授一般化学主题，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，从而提高学生对生物学研究生培训和职业生涯的准备，从而提高化学和生物科学专业学生的保留率，从而培养未被充分代表的群体对生物科学的兴趣。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。这一经验的高潮将是有机会向当地和全国的科学听众介绍科学项目。研究环境对来自服务不足背景的学生特别有吸引力，因为它采用合作模式，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PI的专业发展，同时也将促进少数民族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.