Consortia for High-Throughput-Enabled Structural Biology Partnerships (U01)

高通量结构生物学合作联盟 (U01)

• 批准号: 8153580
• 负责人: STANLEY G NATHENSON
• 金额: $ 97.32万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8153580
• 关键词: Adhesives; Affinity; Amino Acid Sequence; Animal Disease Models; Animal Model; Animals; Area; Autoimmune Diseases; Autoimmunity; Biochemical; Biological; Biological Assay; Biological Models; Biological Process; Biology; CD4 Positive T Lymphocytes; Cell surface; Cells; Commit; Communicable Diseases; Complement; Complex; Cytotoxic T-Lymphocytes; Evolution; Family; Family member; Future; Generations; Goals; Helper-Inducer T-Lymphocyte; Immune; Immune Targeting; Immune response; Immunity; Immunologic Receptors; Immunologist; In Vitro; Individual; Informatics; Knock-in Mouse; Lead; Ligands; Malignant Neoplasms; Memory; Molecular; Natural Immunity; Property; Proteins; Reagent; Regulation; Regulatory T-Lymphocyte; Research Infrastructure; Resolution; Series; Signal Transduction; Specificity; Structural Biologist; Structure; Structure-Activity Relationship; Subgroup; T-Lymphocyte; Therapeutic; Work; adaptive immunity; base; design; expectation; immune function; immunoregulation; in vivo; insight; mouse model; mutant; novel; novel therapeutics; protein complex; receptor; research study; structural biology; tool

The Immune Function Network (IFN), a consortium of immunologists, geneticists, computational biochemists, and high throughput structural biologists, is committed to the coordinated structural, in vitro biochemical and in vivo ftinctional analyses of the secreted molecules and ectodomains of cell surface molecules that control adaptive and innate immunity. These molecules are validated targets for immime-based therapies to treat a wide range of autoimmune diseases, infectious diseases and cancers, and are indeed therapeutics in their own right. The IFN, subscribes to a series of underlying principles: 1) target selection supports hypothesis-driven structural biology by identifying unique primary amino acid sequence signatures that predict unique structural features, which are in turn responsible for unique biological function; 2) the high resolution structures of these molecules are exceptionally revealing as they inform on oligomeric state, valency, specificity and general architectural features, all of which are fundamental mechanistic contributors to immune function; 3) these structures can be readily exploited by biochemical and computational approaches to guide the generation of molecules with specifically altered biochemical and biophysical properties; 4) these "surgically-defined" mutants represent novel reagents that will lead to new mechanistic insights in in vitro cellbased assays and in vivo animal models of disease; 5) the molecules predicted to be most informative will guide the generation of knock-in mouse models to provide in vivo structure-function relationships for innate and adaptive immunity. This "Atoms-to-Animals" approach represents the next step in the evolution of Structural Biology as it maximally leverages structural information and provides a comprehensive and powerful paradigm for the study of normal, pathological, and therapeutic immune responses.

免疫功能网络是一个由免疫学家、遗传学家、计算生物化学家和高级 通过结构生物学家，致力于协调结构、体外生化和体内功能 控制适应性和先天的细胞表面分子的分泌分子和胞外区的分析 豁免权。这些分子是免疫疗法的有效靶点，可用于治疗广泛的自身免疫疾病。 疾病、传染病和癌症，它们本身确实是治疗方法。The IFN，订阅了一系列节目 基本原则：1)目标选择通过识别唯一的原生生物来支持假设驱动的结构生物学 预测独特结构特征的氨基酸序列签名，这反过来又负责唯一的 生物功能；2)这些分子的高分辨率结构非常能揭示 低聚状态、价态、特异性和一般结构特征，所有这些都是基本的机制 免疫功能的贡献者；3)这些结构可以很容易地被生化和计算机利用 指导产生具有特殊生物化学和生物物理性质的分子的方法；4) 这些“手术定义的”突变体代表了新的试剂，将在体外细胞基础上带来新的机制洞察力 疾病的分析和活体动物模型；5)预测最具信息量的分子将指导 为先天和适应性提供体内结构-功能关系的敲入小鼠模型的生成 豁免权。这种“原子到动物”的方法代表了结构生物学进化的下一步，因为它 最大限度地利用结构信息，为研究提供一个全面而强大的范例 正常的、病理的和治疗性的免疫反应。