Laws of mechanics and function in proteins as evolved molecular machines

蛋白质作为进化分子机器的力学定律和功能

• 批准号: 10459896
• 负责人: Lauren McGough
• 金额: $ 6.86万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10459896
• 关键词: 2019-nCoV; Adaptive Immune System; Affinity; Ally; Antibodies; Antibody Diversity; Antibody Response; Antigens; B-Lymphocytes; Bacteria; Biological; Biological Process; Biology; Cells; Clone Cells; Complex; Computer Analysis; Data; Data Analyses; Data Set; Equilibrium; Evolution; Exposure to; Future; Generations; Goals; HIV; Human; Immune system; Immunologic Memory; Immunologics; Individual; Infection; Influenza; Laws; Light; Longevity; Mammals; Mathematical Model Simulation; Mechanics; Memory; Memory B-Lymphocyte; Modeling; Molecular Machines; Mus; Mutate; Mutation; Organism; Outcome; Parasites; Population; Proteins; Research; Scientist; Shapes; Specificity; Structure; Structure of germinal center of lymph node; System; Testing; Theoretical model; Vaccines; Variant; Virus; adaptive immune response; arm; experimental study; interest; mathematical theory; novel; pathogen; predictive test; programs; receptor; response; secondary lymphoid organ; statistics

PROJECT SUMMARY/ABSTRACT The adaptive immune system has evolved to remember primary exposures to specific antigens and launch effective attacks to subsequent exposures. However, rapidly evolving viruses like influenza and HIV present new challenges to the human immune system as they mutate, making them harder to recognize and respond to during subsequent exposures. In order for secondary responses to these pathogens to succeed, the primary response must generate a memory response that balances specificity to the original antigen with diversity against the multitude of possible variants of subsequent exposures. For an individual of a given species interacting with other individuals within a larger population, the efficacy of a given balance between specificity and diversity depends on a number of factors, including how likely the individual is to be exposed to the same pathogen in the future, the rate at which the antigen is mutating, and constraints on the biological processes which control the generation of immunological memory within that species. This research program aims to construct a theoretical framework for characterizing the benefits and trade-offs associated with diversity in the adaptive immune response and the mechanisms by which said diversity is generated. This study will then use computational analyses of several datasets to evaluate the extent to which the antibody responses of different species generate levels of diversity which are well-adapted to their biological needs, using mice and humans as representative examples.

项目概要/摘要 适应性免疫系统已经进化到能够记住特定抗原的初次暴露并启动 对后续暴露进行有效攻击。然而，流感和艾滋病毒等快速进化的病毒存在 随着人类免疫系统发生突变，它们面临新的挑战，使它们更难识别和应对 在随后的暴露过程中。为了成功地对这些病原体进行二次反应，首先 反应必须产生记忆反应，平衡原始抗原的特异性和多样性 针对后续暴露的多种可能变体。对于给定物种的个体 与较大群体中的其他个体互动，特异性之间给定平衡的功效 多样性取决于许多因素，包括个体接触相同内容的可能性有多大 未来的病原体、抗原突变的速度以及对生物过程的限制 控制该物种内免疫记忆的产生。该研究计划旨在 构建一个理论框架来描述与多样性相关的利益和权衡 适应性免疫反应以及产生所述多样性的机制。然后本研究将使用 对多个数据集进行计算分析，以评估不同抗体反应的程度 利用小鼠和人类，物种产生了很好适应其生物需求的多样性水平 作为代表性的例子。