Immune chemistry and therapeutic features of FOXP3

FOXP3 的免疫化学和治疗特征

• 批准号: 7893072
• 负责人: MARK I GREENE
• 金额: $ 140.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7893072
• 关键词: Immune; chemistry; therapeutic; features; FOXP3

DESCRIPTION (provided by applicant): This confederation of projects is headed by Mark I. Greene who has been involved in the study of immune regulation and phenotype reversal for over 30 years. The goals of this highly integrated program project are to develop understanding of how the FoxpS proteins exert their biological effects and through this knowledge to develop translationally relevant therapeutics that disable or activate the Foxp3 complex. Although the theme of Foxp3 function resonates in each project, a variety of distinct technologies are actually employed to develop insights into how Foxp3 complexes operate and how to manipulate them, leading to a highly interactive group of experiments that should lead to therapeutics that will reach the clinic within the time frame of this program project. The long-term goals are reiterated in every project and all projects share recurrent themes of Treg phenotype manipulation. The studies to date have already lead to a rational therapeutic for autoimmune conditions that is entering a preliminary clinical trial at the NIH. The goal of Greene's project is to provide basic biochemical information of how the Foxp3 complex binds to chromatin in human cells. This information will be helpful in Andrew Wells's study of mouse chromatin - Foxp3 interactions and will be useful in the creation of transgenic and mutant mice that will help the Hancock project and the Wells project. Human and mouse Foxp3 complexes appear to have differences although both form large ensembles. The intent of Project 1 is to identify individual residues that are acetylated and phosphorylated and subdomains that mediate interactions with other repressive components. This information will provide a framework for Andrew Wells to examine chromatin remodeling events in the mouse and for Wayne Hancock to examine functional relevance in in vivo models.

描述（由申请人提供）：该项目的这种联邦由马克·格林（Mark I.这个高度综合的程序项目的目标是发展对FOXP蛋白如何发挥其生物学作用的理解，并通过这种知识来开发与翻译相关的治疗剂，从而禁用或激活FOXP3复合物。尽管FOXP3功能的主题在每个项目中引起了共鸣，但实际上采用了各种不同的技术来开发有关Foxp3复合物如何运作以及如何操纵它们的见解，从而导致一组高度互动的实验组，这些实验应该导致该计划项目的时间范围内到达诊所。每个项目都重申了长期目标，所有项目都共享Treg表型操纵的经常性主题。迄今为止，这些研究已经导致对自身免疫性疾病的合理治疗，该治疗正在NIH进入初步临床试验。 格林项目的目标是提供有关FOXP3复合物如何与人类细胞染色质结合的基本生化信息。这些信息将在安德鲁·威尔斯（Andrew Wells）对小鼠染色质-FOXP3相互作用的研究中有所帮助，并且将有助于创建转基因和突变小鼠，这将有助于Hancock Project和Wells Project。人类和小鼠Foxp3复合物似乎有差异，尽管两者都形成了大型合奏。 项目1的目的是识别乙酰化和磷酸化的单个残基，并介导与其他抑制成分相互作用的亚域。该信息将为安德鲁·威尔斯（Andrew Wells）提供一个框架，以检查鼠标和韦恩·汉考克（Wayne Hancock）中的染色质重塑事件，以检查体内模型中的功能相关性。