GOALI: Collaborative Proposal: Mechanistic Design of Aggregation Resistance in Multi-Domain Proteins
GOALI:合作提案:多域蛋白质抗聚集的机制设计
基本信息
- 批准号:1264554
- 负责人:
- 金额:$ 25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-15 至 2017-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Roberts/Robinson1264329/1264554 Non-native aggregation denotes a set of molecular processes by which a folded, biologically active protein becomes effectively locked into a ?misfolded? assembly or aggregate of proteins. Formation of these aggregates is a ubiquitous hurdle to successful over-expression, purification, and storage of recombinant proteins throughout the biotechnology and biopharmaceutical industries. This is particularly the case for multi-domain proteins, such as natural and designed antibodies, as well as for other predominantly-beta proteins. Predictive design of these more complex proteins is handicapped by limitations in the mechanistic understanding of key features of sequence and structure that control aggregation of multi-domain proteins. This project seeks to improve fundamental understanding of the mechanism(s) of multi-domain protein aggregation, so as to provide general design rules to engineer aggregation resistance into therapeutic proteins and other biotechnology products. This is a partnership between Amgen, Tulane University, and the University of Delaware through the National Science Foundation?s industry-university GOALI program. The work will focus on computational design of new antibody molecules that retain their known function (e.g., ligand binding) while greatly reducing their aggregation rates, and then experimentally characterizing the aggregation pathways to assure that the design predictions worked properly at a molecular level. From a broader perspective, the project focuses on creating new experimental and computational tools to better predict and control or even eliminate aggregates in protein pharmaceuticals and other biotechnology products. Doing so will decrease the cost of development for industrial scientists and engineers, and also decrease the time to market and any safety risks associated with protein aggregates in medical applications. The biopharmaceutical industry is one the fastest growing and attractive industries for growth of the U.S. job market requiring a highly trained workforce that will maintain international competitiveness. An indirect but equally important outcome of this project is the training of the next generation of industrial scientists and potential leaders for the industry, as well as development of new educational tools for more broad use throughout the technical community, and potentially for direct use in demonstrations in high school science courses such as chemistry, biochemistry, biology, and physics.
Roberts/Robinson 1264329/1264554非天然聚集是指一组分子过程,通过这些过程,折叠的生物活性蛋白质有效地锁定在一个?折错了蛋白质的装配或聚集。 这些聚集体的形成是整个生物技术和生物制药工业中重组蛋白成功过表达、纯化和储存的普遍障碍。对于多结构域蛋白质,例如天然和设计的抗体,以及其他主要的β蛋白质,情况尤其如此。 这些更复杂的蛋白质的预测设计受到限制,在控制多结构域蛋白质聚集的序列和结构的关键特征的机械理解。该项目旨在提高对多结构域蛋白质聚集机制的基本理解,从而提供通用设计规则,以将抗聚集性工程化到治疗性蛋白质和其他生物技术产品中。这是安进公司、杜兰大学和特拉华州大学通过国家科学基金会建立的伙伴关系?的工业大学GOALI计划。这项工作将集中在保留其已知功能的新抗体分子的计算设计上(例如,配体结合),同时大大降低它们的聚集速率,然后通过实验表征聚集途径,以确保设计预测在分子水平上正常工作。 从更广泛的角度来看,该项目侧重于创建新的实验和计算工具,以更好地预测和控制甚至消除蛋白质药物和其他生物技术产品中的聚集体。 这样做将降低工业科学家和工程师的开发成本,并减少上市时间和与医疗应用中蛋白质聚集体相关的任何安全风险。 生物制药行业是美国就业市场增长最快和最具吸引力的行业之一,需要训练有素的劳动力来保持国际竞争力。 该项目的一个间接但同样重要的成果是培训下一代工业科学家和潜在的行业领导者,以及开发新的教育工具,供整个技术社区更广泛地使用,并可能直接用于高中科学课程的演示,如化学,生物化学,生物学和物理学。
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 }}
Anne Robinson其他文献
R142: The Effects of Sensory Deprivation on Olfactory Thresholds
- DOI:
10.1016/j.otohns.2007.06.478 - 发表时间:
2007-08-01 - 期刊:
- 影响因子:
- 作者:
Julian Anthony Gaskin;Anne Robinson;Carl M. Philpott;Paul C. Goodenough;Allan Clark;George E. Murty - 通讯作者:
George E. Murty
The evolving nature of narcotic use in northwestern Ontario.
安大略省西北部麻醉品使用性质的演变。
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:1.1
- 作者:
Jazmyn Balfour;Sara Rea;Janet N Gordon;J. Dooley;L. Kelly;Anne Robinson - 通讯作者:
Anne Robinson
Sa1208 Sustained Efficacy in Patients With Ulcerative Colitis Treated With Adalimumab: Results From ULTRA 2
- DOI:
10.1016/s0016-5085(13)60814-8 - 发表时间:
2013-05-01 - 期刊:
- 影响因子:
- 作者:
Subrata Ghosh;Douglas C. Wolf;William Sandborn;Jean-Frederic Colombel;Qian Zhou;Andreas Lazar;Samantha Eichner;Anne Robinson;Roopal Thakkar - 通讯作者:
Roopal Thakkar
Sa1213 Safety of Adalimumab in Global Clinical Trials of Ulcerative Colitis Patients
- DOI:
10.1016/s0016-5085(13)60819-7 - 发表时间:
2013-05-01 - 期刊:
- 影响因子:
- 作者:
Jean-Frederic Colombel;Subrata Ghosh;William Sandborn;Gert A. Van Assche;Walter Reinisch;Andreas Lazar;Samantha Eichner;Bidan Huang;Anne Robinson;Roopal Thakkar - 通讯作者:
Roopal Thakkar
The value of PubMed and HighWire Press for the busy general practitioner
PubMed 和 HighWire Press 对于忙碌的全科医生的价值
- DOI:
10.18773/austprescr.2004.010 - 发表时间:
2004 - 期刊:
- 影响因子:2.7
- 作者:
Anne Robinson;S. Day - 通讯作者:
S. Day
Anne Robinson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('Anne Robinson', 18)}}的其他基金
Collaborative Proposal: Exploiting synthetic GPCRs and mating factors as extracellular sensors for substrate-dependent assembly of complex cellulosomes
合作提案:利用合成 GPCR 和交配因子作为细胞外传感器,用于复杂多纤维素酶体的底物依赖性组装
- 批准号:
1263768 - 财政年份:2013
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
Understanding trafficking and membrane localization to re-engineer host and GPCR protein for improved expression
了解运输和膜定位以重新设计宿主和 GPCR 蛋白以改善表达
- 批准号:
1249200 - 财政年份:2012
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
Understanding trafficking and membrane localization to re-engineer host and GPCR protein for improved expression
了解运输和膜定位以重新设计宿主和 GPCR 蛋白以改善表达
- 批准号:
1033268 - 财政年份:2010
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
Biochemical Engineering XVI: Past, Present, and Future. Held in Burlington, VT from July 5-9, 2009
生物化学工程十六:过去、现在和未来。
- 批准号:
0936044 - 财政年份:2009
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
IGERT: Multidisciplinary Graduate Progrqam in Biotechnology
IGERT:生物技术多学科研究生课程
- 批准号:
0221651 - 财政年份:2002
- 资助金额:
$ 25万 - 项目类别:
Continuing Grant
CAREER: Characterization, Inhibition, and Reversal of Protein Aggregation
职业:蛋白质聚集的表征、抑制和逆转
- 批准号:
9984312 - 财政年份:2000
- 资助金额:
$ 25万 - 项目类别:
Continuing Grant
POWRE: Molecular Determinants and Inhibition of Protein Aggregation
POWRE:分子决定因素和蛋白质聚集的抑制
- 批准号:
9720570 - 财政年份:1997
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
相似海外基金
GOALI: Collaborative Proposal: Novel approaches to model travel behavior and sustainability impacts of e-bike use
目标:协作提案:对出行行为和电动自行车使用的可持续性影响进行建模的新方法
- 批准号:
1706695 - 财政年份:2018
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI: Collaborative Proposal: Novel approaches to model travel behavior and sustainability impacts of e-bike use
目标:协作提案:对出行行为和电动自行车使用的可持续性影响进行建模的新方法
- 批准号:
1706939 - 财政年份:2018
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI Collaborative Proposal: 3D RF Microsystems using Direct Digital Manufacturing Technology
GOALI 协作提案:使用直接数字制造技术的 3D RF 微系统
- 批准号:
1648657 - 财政年份:2016
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI Collaborative Proposal: 3D RF Microsystems using Direct Digital Manufacturing Technology
GOALI 协作提案:使用直接数字制造技术的 3D RF 微系统
- 批准号:
1231869 - 财政年份:2012
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI Collaborative Proposal: 3D RF Microsystems using Direct Digital Manufacturing Technology
GOALI 协作提案:使用直接数字制造技术的 3D RF 微系统
- 批准号:
1232183 - 财政年份:2012
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI /RUI Collaborative Proposal - Measurements and Modeling for Improved Performance of Batch Slurry Processes
GOALI /RUI 合作提案 - 测量和建模以提高批量浆料工艺的性能
- 批准号:
0750287 - 财政年份:2008
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI/RUI Collaborative Proposal - Measurements and Modeling for Improved Performance of Batch Slurry Processes
GOALI/RUI 协作提案 - 提高间歇式浆料工艺性能的测量和建模
- 批准号:
0750333 - 财政年份:2008
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI : Collaborative Proposal: Advanced Coding and Signal Processing for Magnetic Recording: From Theory to Implementation
目标:协作提案:磁记录的高级编码和信号处理:从理论到实现
- 批准号:
0802159 - 财政年份:2008
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI/RUI Collaborative Proposal - Characterization and Modeling for Improved Performance of Batch Slurry Processes
GOALI/RUI 协作提案 - 表征和建模以提高间歇式浆料工艺的性能
- 批准号:
0750364 - 财政年份:2008
- 资助金额:
$ 25万 - 项目类别:
Standard Grant
GOALI : Collaborative Proposal: Advanced Coding and Signal Processing
目标:协作提案:高级编码和信号处理
- 批准号:
0802124 - 财政年份:2008
- 资助金额:
$ 25万 - 项目类别:
Standard Grant