Detecting RORgt Citrullination

检测 RORgt 瓜氨酸化

• 批准号: 10304200
• 负责人: I-CHENG HO
• 金额: $ 8.56万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-17 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304200
• 关键词: Address; Affect; Amino Acids; Antibodies; Arginine; Attenuated; Autoimmune Diseases; Autoimmunity; Cell physiology; Cells; Citrulline; Clinical; DNA Binding; Detection; Future; GATA3 gene; Generations; Genetic Transcription; Genomics; Goals; Health; Human; Immune response; Infection; Inflammation; Invaded; Knowledge; Lymphocyte; Lymphocyte Function; Mammals; Mediating; Modification; Monoclonal Antibodies; Names; Pathogenicity; Peptides; Play; Post-Translational Protein Processing; Process; Protein-arginine deiminase; Proteins; Reagent; Regulation; Regulatory T-Lymphocyte; Role; Site; Site-Directed Mutagenesis; Th2 Cells; Untranslated RNA; Western Blotting; design; experimental study; human disease; immune function; improved; neutrophil; new therapeutic target; novel strategies; polyclonal antibody; protein function; tool; transcription factor

Project Summary Many proteins are modified after they are produced in cells. Such modification can critically influence the function of proteins. One such modification is citrullination, which has been shown to regulate the function of immune cells, including lymphocytes and neutrophils. Abnormal citrullination has been associated with many human diseases, including infection and autoimmune diseases. Thus, manipulating protein citrullination can be beneficial in many clinical settings; however, our knowledge of citrullination is still very limited mainly due to lack of sensitive and specific tool for detecting citrullination. The objectives of this project are to develop a reagent that can reliably detect the citrullination of a protein named RORgt, which is important for the differentiation/function of lymphocytes, and to demonstrate the value of this reagent in a proof-of-principle experiment. The reagent thus generated will be a powerful tool for future studies on the regulatory roles of citrullination in the function of lymphocytes and very likely will lead to discoveries of novel therapeutic targets of human diseases.

项目摘要 许多蛋白质在细胞中产生后被修饰。这种改变会严重影响 蛋白质的功能。一种这样的修饰是瓜氨酸，其已被证明可以调节 免疫细胞，包括淋巴细胞和中性粒细胞。瓜氨酸异常与许多 人类疾病，包括感染和自身免疫性疾病。因此，操纵瓜氨酸蛋白可以是 在许多临床环境中有益;然而，我们对瓜氨酸的了解仍然非常有限，主要原因是 缺乏检测瓜氨酸敏感和特异性工具。该项目的目标是开发一个 该试剂可以可靠地检测一种名为RORgt的蛋白质的瓜氨酸酶，这对 淋巴细胞的分化/功能，并证明该试剂在原理验证中的价值 实验该试剂为进一步研究基因的调控作用提供了有力的工具。 瓜氨酸在淋巴细胞功能中的作用，很可能会导致发现新的治疗靶点， 人类疾病。