Project 4: Novel reagent development to enable molecular characterization
项目 4:开发新型试剂以实现分子表征
基本信息
- 批准号:10359195
- 负责人:
- 金额:$ 44.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-15 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AffinityAge-associated memory impairmentAlgorithmsAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAmino AcidsAmyloidAmyloid beta-ProteinAntibodiesBindingBinding ProteinsBiological AssayBiological MarkersBrain-Derived Neurotrophic FactorCerebrospinal FluidCerebrospinal Fluid ProteinsClinicalCollaborationsComplementData Storage and RetrievalDetectionDevelopmentDiagnosticEngineeringFeedbackFunctional disorderGoalsGreen Fluorescent ProteinsLengthLogicMeasuresMethodsMolecularMonoclonal AntibodiesNeurodegenerative DisordersOutcomeParkinson DiseasePeptidesProductionProtein EngineeringProteinsReagentResearchResourcesSamplingSeriesSpecific qualifier valueSpecificityStatistical Data InterpretationSurfaceSystemTestingWorkage related neurodegenerationalpha synucleinbasedata disseminationdata sharingdesigndetection platformexperimental studyimprovedneurograninnext generationnovelparticleprogramsprotein biomarkerstargeted biomarkertranslational proteomics
项目摘要
Abstract
Project 4 will test the hypothesis that computationally designed protein “minibinders” and logic-gated switches
targeting cerebrospinal fluid (CSF) protein biomarkers and protein particles can serve as versatile capture and
detection agents to vastly improve the molecular characterization of CSF samples. The availability of these
reagents should support the overall U19 goal of improving our understanding of CSF biomarkers as direct
measures of age-related cognitive decline and Alzheimer's Disease (AD) pathophysiology.
We have integrated our work plan within the highly focused U19 Project: Next Generation Translational
Proteomics for Alzheimer's and Related Dementias to test the above hypothesis. In collaboration with Projects
1–3, our main goal is to develop an optimized set of computationally designed minibinders (hyperstable binding
proteins of length <65 aa) as CSF protein biomarker capture agents, and ultra-specific logic-gated reagents for
detection of CSF particles that have two defined protein components.
The research will iterate between computational design and experimental testing, with feedback at each stage
from CSF assay experiments conducted in collaboration with Projects 1-3 which will guide improvement of the
minibinder design methods for capture of specified CSF biomarker protein targets, and for ultra-specific logic-
gated detection of CSF particles with two composite protein components. The outcomes will be (i) specific CSF
biomarker capture and detection systems for AD and other age-related neurodegenerative disorders, and (ii)
an integrated computational-experimental pipeline for rapid on demand engineering of new protein based
diagnostic agents for neurodegenerative disorders in general. Therefore, Project 4 relies on a close
collaboration with Projects 1-3 and Cores 1-4 within the highly interactive U19 program.
摘要
项目4将测试假设,计算设计的蛋白质“minibinders”和逻辑门控开关
靶向脑脊液(CSF)蛋白质生物标志物和蛋白质颗粒可用作通用捕获和
检测试剂,以极大地改善CSF样品的分子表征。网站或资源的可用性
试剂应支持U19的总体目标,即提高我们对CSF生物标志物的理解,
与年龄相关的认知衰退和阿尔茨海默病(AD)病理生理学的测量。
我们已经将我们的工作计划整合到高度集中的U19项目中:下一代翻译
阿尔茨海默氏症和相关痴呆症的蛋白质组学来验证上述假设。与项目合作
1-3,我们的主要目标是开发一组优化的计算设计的minibinders(超稳定绑定
长度<65 aa的蛋白质)作为CSF蛋白质生物标志物捕获剂,以及用于
检测具有两种确定的蛋白质组分的CSF颗粒。
研究将在计算设计和实验测试之间进行,每个阶段都有反馈
从与项目1-3合作进行的CSF测定实验中,
用于捕获特定CSF生物标志物蛋白靶点和用于超特异性逻辑分析的微结合物设计方法
具有两种复合蛋白组分的CSF颗粒的门控检测。结局将是(i)特定CSF
用于AD和其他年龄相关的神经退行性疾病的生物标志物捕获和检测系统,和(ii)
一个集成的计算实验管道,用于快速按需工程化新蛋白质,
一般用于神经变性疾病的诊断剂。因此,项目4依赖于关闭
与高度互动的U19计划中的项目1-3和核心1-4合作。
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)
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{{ truncateString('DAVID BAKER', 18)}}的其他基金
De Novo Design of Minibinder Antagonists for COVID-19 and Future Pandemics
针对 COVID-19 和未来大流行病的 Minibinder 拮抗剂的从头设计
- 批准号:
10296596 - 财政年份:2021
- 资助金额:
$ 44.88万 - 项目类别:
De Novo Design of Minibinder Antagonists for COVID-19 and Future Pandemics
针对 COVID-19 和未来大流行病的 Minibinder 拮抗剂的从头设计
- 批准号:
10460648 - 财政年份:2021
- 资助金额:
$ 44.88万 - 项目类别:
De Novo Design of Minibinder Antagonists for COVID-19 and Future Pandemics
针对 COVID-19 和未来大流行病的 Minibinder 拮抗剂的从头设计
- 批准号:
10672446 - 财政年份:2021
- 资助金额:
$ 44.88万 - 项目类别:
Project 4: Novel reagent development to enable molecular characterization
项目 4:开发新型试剂以实现分子表征
- 批准号:
10573273 - 财政年份:2020
- 资助金额:
$ 44.88万 - 项目类别:
Designed Vehicles for Blood Brain Barrier Traversal
设计用于穿越血脑屏障的车辆
- 批准号:
10400878 - 财政年份:2019
- 资助金额:
$ 44.88万 - 项目类别:
Designed Vehicles for Blood Brain Barrier Traversal
设计用于穿越血脑屏障的车辆
- 批准号:
10200639 - 财政年份:2019
- 资助金额:
$ 44.88万 - 项目类别:
Design of de novo interleukin mimics for targeted immunotherapy
用于靶向免疫治疗的从头白细胞介素模拟物的设计
- 批准号:
9796930 - 财政年份:2019
- 资助金额:
$ 44.88万 - 项目类别:
Designed Vehicles for Blood Brain Barrier Traversal
设计用于穿越血脑屏障的车辆
- 批准号:
10614470 - 财政年份:2019
- 资助金额:
$ 44.88万 - 项目类别:
Design of de novo interleukin mimics for targeted immunotherapy
用于靶向免疫治疗的从头白细胞介素模拟物的设计
- 批准号:
10475003 - 财政年份:2019
- 资助金额:
$ 44.88万 - 项目类别:
Designed Vehicles for Blood Brain Barrier Traversal
设计用于穿越血脑屏障的车辆
- 批准号:
9796948 - 财政年份:2019
- 资助金额:
$ 44.88万 - 项目类别:
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