Structural biology of antibody:antigen complexes
抗体的结构生物学:抗原复合物
基本信息
- 批准号:8377204
- 负责人:
- 金额:$ 25.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-08-01 至 2016-07-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAntibodiesAntigen-Antibody ComplexAntigensB cell repertoireBindingCharacteristicsComplexCryoelectron MicroscopyDevicesDissectionEpitopesExposure toFoundationsGlycoproteinsGoalsImmune responseImmunizationImmunodominant EpitopesInfectionInfluenza HemagglutininInstructionKnowledgeLeadLinkMapsMethodsProteinsResolutionRotavirusStructureTechnologyTestingVaccinationVaccinesViral AntigensVirusWorkbasedesigninfluenzavirusnovelparticlereconstructionresponsescaffoldstructural biologyvaccine development
项目摘要
The overall goals of Project 3 are to understand the high-resolution structural correlates of immunodominance
and to provide structural foundations for designing immunogens that can focus an immune response on
particular, chosen epitopes. Our principal hypothesis is that structural contributions to immunodominance can
be revealed by correlating structures of antibody-antigen complexes with knowledge of the repertoire from
which the antibody was derived and reconstruction of the mutational sequence that led to the affinity matured
antibody from its germline precursor. The high-throughput approaches described in Project 1 can give us the
required information about repertoire and about affinity maturation of antibodies denved from the settings of
vaccination vs. infection. We propose here to provide the corresponding three-dimensional information. We
have the following four Aims. [1) What are the structural characteristics of cross-reactive antibodies bound with
their HA epitopes? We will determine structures of selected representatives of the antibodies studied in projects
1 and 2, in complex with the relevant influenza virus HA. We will begin with standard crystallographic
approaches, but proceed as rapidly as possible to higher-throughput cryoEM methods (Aim 2; see also Core C).
(2) We will develop approaches for mounting "guest proteins" [with influenza HA as the principal target) onto
icosahedral-virus scaffolds, to create a symmetric array suitable for structure determination by cryoEM. We will
start with the rotavirus double-layer particle (DLP) as our scaffold, and the outer-layer glycoprotein, VP7, as the
mounting device.; we will also test the other outer-layer protein, VP4, as a trimeric mounting protein. [3) What
makes an epitope immunodominant? The opportunity afforded by the cryoEM approach to examine a
systematic and relatively unbiased set of complexes will allow us to determine the structural correlates of
immunodominance directly. We will determine structures of a selected HA in complex with antibodies
representing the entire spectrum of a typical repertoire as revealed by the studies in Project 1 and mapped by
Project 2. [4) Application to other viral antigens. We will apply to the mounting strategies developed in Aim 2 to
other viral antigens for which a combination of repertoire analysis and structural dissection might lead to novel
项目3的总体目标是了解免疫优势的高分辨率结构相关性
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
STEPHEN COPLAN HARRISON其他文献
STEPHEN COPLAN HARRISON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('STEPHEN COPLAN HARRISON', 18)}}的其他基金
Structural biology of antibody:antigen complexes
抗体的结构生物学:抗原复合物
- 批准号:
8516984 - 财政年份:2013
- 资助金额:
$ 25.45万 - 项目类别:
Discovery of small molecules to block fusion and entry of dengue and other env vi
发现小分子以阻止登革热和其他环境病毒的融合和进入
- 批准号:
8233434 - 财政年份:2011
- 资助金额:
$ 25.45万 - 项目类别:
Structural biology of antibody:antigen complexes
抗体的结构生物学:抗原复合物
- 批准号:
8329266 - 财政年份:2011
- 资助金额:
$ 25.45万 - 项目类别:
Project 4: Structural Biology of Influenza Antibody-Antigen Interactions
项目4:流感抗体-抗原相互作用的结构生物学
- 批准号:
10549614 - 财政年份:2011
- 资助金额:
$ 25.45万 - 项目类别:
Structure-function analysis of infection- and vaccine-induced B-cell repertoires
感染和疫苗诱导的 B 细胞库的结构功能分析
- 批准号:
10549602 - 财政年份:2011
- 资助金额:
$ 25.45万 - 项目类别:
Structure-function analysis of infection- and vaccine-induced B-cell repertoires
感染和疫苗诱导的 B 细胞库的结构功能分析
- 批准号:
8516979 - 财政年份:2011
- 资助金额:
$ 25.45万 - 项目类别:
相似海外基金
University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
- 批准号:
10073243 - 财政年份:2024
- 资助金额:
$ 25.45万 - 项目类别:
Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
- 批准号:
10752129 - 财政年份:2024
- 资助金额:
$ 25.45万 - 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
- 批准号:
2339201 - 财政年份:2024
- 资助金额:
$ 25.45万 - 项目类别:
Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 25.45万 - 项目类别:
Research Grant
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
- 批准号:
10076445 - 财政年份:2023
- 资助金额:
$ 25.45万 - 项目类别:
Grant for R&D
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
- 批准号:
23K14783 - 财政年份:2023
- 资助金额:
$ 25.45万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
- 批准号:
23KJ0394 - 财政年份:2023
- 资助金额:
$ 25.45万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Role of antibodies in hepatitis E virus infection
抗体在戊型肝炎病毒感染中的作用
- 批准号:
10639161 - 财政年份:2023
- 资助金额:
$ 25.45万 - 项目类别:
Defining the protective or pathologic role of antibodies in Post-Ebola Syndrome
定义抗体在埃博拉后综合症中的保护或病理作用
- 批准号:
10752441 - 财政年份:2023
- 资助金额:
$ 25.45万 - 项目类别:
Human CMV monoclonal antibodies as therapeutics to inhibit virus infection and dissemination
人 CMV 单克隆抗体作为抑制病毒感染和传播的治疗药物
- 批准号:
10867639 - 财政年份:2023
- 资助金额:
$ 25.45万 - 项目类别: