Collaborative Research: EAGER: Uncovering the role of Golgi organization on function

合作研究:EAGER:揭示高尔基组织对功能的作用

基本信息

  • 批准号:
    1935370
  • 负责人:
  • 金额:
    $ 18.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-08-15 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Synthetic cell engineering has the potential to reveal insights into the fundamental chemical and physical processes that underlie the function of biological cells and organelles as well as advance the design of biologically-inspired devices and materials with applications ranging from medicine to biotechnology. Recently, it has become clear that the function of many proteins and lipids in biological cells depends on posttranslational modifications, covalent additions to the surface of proteins after their synthesis. A majority of these modifications are performed by the Golgi apparatus, a central membrane organelle in mammalian cells with a unique and dynamically changing structure. Yet neither the features of the Golgi that facilitate the synthesis of these highly complex chemical structures nor how those reactions are spatially and temporally controlled is fully understood. To better understand the regulatory mechanisms of the Golgi structure, this proposal will reconstitute chemical and physical features of the Golgi in an in vitro system. This proposal will develop new strategies to uncover how physical features of membranes influence an essential posttranslational modification, glycosylation. Specifically, it will recreate a model multi-step glycosylation modification of lipid carriers in vitro using both microfluidic and vesicle-based platforms and uncover the rules of membrane spatial and physical features required to recapitulate the posttranslational modification process. Successful completion of these studies will reveal design rules that will enable creation of other posttranslational modifications through re-organization of these reactions, including synthetic modifications. With these insights, it will be possible to extend these findings to influence the activity and function of modified proteins and lipids in order to impact biological processes. This project will bridge a variety of interdisciplinary techniques in membrane biophysics, membrane protein reconstitution, protein engineering, microfluidics, transport phenomena, and chemical kinetics necessary to realize the project goals. The knowledge developed here will benefit the biotechnology and pharmaceutical industries and have potential biomanufacturing applications in the design of therapeutic compounds. This project is jointly funded by the Cellular Dynamics and Function and Systems and Synthetic Biology Clusters, Division of Molecular and Cellular Biosciences, Directorate for Biological Sciences and by the Cellular and Biochemical Engineering Program, Division of Chemical, Bioengineering, Environmental and Transport Systems, Directorate for Engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
合成细胞工程有可能揭示生物细胞和细胞器功能基础的基本化学和物理过程,并推进生物启发设备和材料的设计,应用范围从医学到生物技术。最近,已经清楚的是,生物细胞中的许多蛋白质和脂质的功能取决于翻译后修饰,即在蛋白质合成后共价添加到蛋白质表面。大多数这些修改是由高尔基体,一个中央膜细胞器在哺乳动物细胞中具有独特的和动态变化的结构。然而,无论是促进这些高度复杂的化学结构合成的高尔基体的特征,还是这些反应在空间和时间上是如何控制的,都没有得到充分的理解。为了更好地了解高尔基体结构的调控机制,本研究将在体外系统中重建高尔基体的化学和物理特征。这项建议将开发新的策略,以揭示膜的物理特性如何影响一个重要的翻译后修饰,糖基化。具体而言,它将使用微流体和基于囊泡的平台在体外重建脂质载体的多步糖基化修饰模型,并揭示再现翻译后修饰过程所需的膜空间和物理特征的规则。这些研究的成功完成将揭示设计规则,这些规则将使通过重组这些反应,包括合成修饰,创造其他翻译后修饰成为可能。有了这些见解,将有可能扩展这些发现,以影响修饰蛋白质和脂质的活性和功能,从而影响生物过程。该项目将在膜生物物理学,膜蛋白质重组,蛋白质工程,微流体,运输现象和化学动力学实现项目目标所需的各种跨学科技术之间架起桥梁。这里开发的知识将有利于生物技术和制药工业,并在治疗化合物的设计中具有潜在的生物制造应用。该项目由生物科学理事会分子和细胞生物科学部细胞动力学、功能和系统及合成生物学集群以及化学、生物工程、环境和运输系统部细胞和生物化学工程项目共同资助,该奖项反映了NSF的法定使命,并被认为是值得通过评估使用基金会的知识优点和更广泛的影响审查标准。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Small tools for sweet challenges: advances in microfluidic technologies for glycan synthesis
Cell-Free Synthesis of a Transmembrane Mechanosensitive Channel Protein into a Hybrid-Supported Lipid Bilayer
将跨膜机械敏感通道蛋白无细胞合成到混合支持的脂质双层中
  • DOI:
    10.1021/acsabm.0c01482
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    4.7
  • 作者:
    Manzer, Zachary A.;Ghosh, Surajit;Jacobs, Miranda L.;Krishnan, Srinivasan;Zipfel, Warren R.;Piñeros, Miguel;Kamat, Neha P.;Daniel, Susan
  • 通讯作者:
    Daniel, Susan
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Susan Daniel其他文献

Membrane protein synthesis: no cells required
膜蛋白合成:不需要细胞
  • DOI:
    10.1016/j.tibs.2023.03.006
  • 发表时间:
    2023-07-01
  • 期刊:
  • 影响因子:
    11.000
  • 作者:
    Zachary A. Manzer;Ekaterina Selivanovitch;Alexis R. Ostwalt;Susan Daniel
  • 通讯作者:
    Susan Daniel
Studying Fusion of Influenza to Supported Lipid Bilayers using Individual Virion Imaging Techniques
  • DOI:
    10.1016/j.bpj.2011.11.2332
  • 发表时间:
    2012-01-31
  • 期刊:
  • 影响因子:
  • 作者:
    Deirdre A. Costello;Susan Daniel
  • 通讯作者:
    Susan Daniel
A reconstitutive platform for biophysical dissection of the Nipah virus fusion cascade
  • DOI:
    10.1016/j.bpj.2023.11.1517
  • 发表时间:
    2024-02-08
  • 期刊:
  • 影响因子:
  • 作者:
    Sreetama Pal;Hector C. Aguilar;Susan Daniel
  • 通讯作者:
    Susan Daniel
Recreating the Biological Steps of Viral Infection on a Bioelectronic Platform to Profile Viral Variants of Concern
在生物电子平台上重现病毒感染的生物学步骤,以分析值得关注的病毒变体
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Zhongmou Chao;Ekaterina Selivanovitch;K. Kallitsis;Zixuan Lu;Ambika Pachaury;Róisín M. Owens;Susan Daniel
  • 通讯作者:
    Susan Daniel
Impedance sensing of antibiotic interactions with a pathogenic emE. coli/em outer membrane supported bilayer
抗生素与致病性大肠杆菌外膜支持的双层膜相互作用的阻抗传感
  • DOI:
    10.1016/j.bios.2022.114045
  • 发表时间:
    2022-05-15
  • 期刊:
  • 影响因子:
    10.500
  • 作者:
    Surajit Ghosh;Zeinab Mohamed;Jung-Ho Shin;Samavi Farnush Bint E Naser;Karan Bali;Tobias Dörr;Róisín M. Owens;Alberto Salleo;Susan Daniel
  • 通讯作者:
    Susan Daniel

Susan Daniel的其他文献

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{{ truncateString('Susan Daniel', 18)}}的其他基金

NSF/MCB-BSF: Revealing the steps and modulators of coronavirus fusion using single-molecule tools
NSF/MCB-BSF:使用单分子工具揭示冠状病毒融合的步骤和调节剂
  • 批准号:
    2207688
  • 财政年份:
    2022
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
I-Corps: Cell-free Biosensors
I-Corps:无细胞生物传感器
  • 批准号:
    2229505
  • 财政年份:
    2022
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
2020 SynCell Meeting
2020 SynCell 会议
  • 批准号:
    2024029
  • 财政年份:
    2020
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
RAPID: Revealing the intermolecular interactions between the SARS-CoV-2/COVID-19 fusion peptide and the host cell membrane that underlie its flexibility in host tropism
RAPID:揭示 SARS-CoV-2/COVID-19 融合肽与宿主细胞膜之间的分子间相互作用,这是其宿主向性灵活性的基础
  • 批准号:
    2027070
  • 财政年份:
    2020
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
EAGER: Plant membrane on-a-chip for the genome wide studies of plant transport processes
EAGER:芯片上的植物膜,用于植物运输过程的全基因组研究
  • 批准号:
    2016107
  • 财政年份:
    2020
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
Bio-nanomanufacturing of Protein Therapeutics Using Membrane Microfluidics
使用膜微流体的蛋白质治疗药物的生物纳米制造
  • 批准号:
    1728049
  • 财政年份:
    2017
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
Collaborative Research: Microbial Fuel Cell Optimization through Digital Microfluidic Electrochemistry in Single-Bacterial Drops
合作研究:通过单细菌液滴中的数字微流体电化学优化微生物燃料电池
  • 批准号:
    1605787
  • 财政年份:
    2016
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
ISS: Unmasking contact-line mobility for Inertial Spreading using Drop Vibration and Coalescence
国际空间站:利用液滴振动和聚结揭示惯性传播的接触线移动性
  • 批准号:
    1637960
  • 财政年份:
    2016
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
Viral coat protein arrays for rapid development and screening of anti-fusogenic antivirals against Ebolavirus
用于快速开发和筛选埃博拉病毒抗融合抗病毒药物的病毒外壳蛋白阵列
  • 批准号:
    1504846
  • 财政年份:
    2015
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Standard Grant
A Single Particle Imaging Approach for the Detection of Virus Phenotypes in a Mixture
用于检测混合物中病毒表型的单粒子成像方法
  • 批准号:
    1263701
  • 财政年份:
    2013
  • 资助金额:
    $ 18.31万
  • 项目类别:
    Continuing Grant

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相似海外基金

Collaborative Research: EAGER: IMPRESS-U: Groundwater Resilience Assessment through iNtegrated Data Exploration for Ukraine (GRANDE-U)
合作研究:EAGER:IMPRESS-U:通过乌克兰综合数据探索进行地下水恢复力评估 (GRANDE-U)
  • 批准号:
    2409395
  • 财政年份:
    2024
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    $ 18.31万
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    Standard Grant
EAGER/Collaborative Research: An LLM-Powered Framework for G-Code Comprehension and Retrieval
EAGER/协作研究:LLM 支持的 G 代码理解和检索框架
  • 批准号:
    2347624
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    2024
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    $ 18.31万
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    Standard Grant
EAGER/Collaborative Research: Revealing the Physical Mechanisms Underlying the Extraordinary Stability of Flying Insects
EAGER/合作研究:揭示飞行昆虫非凡稳定性的物理机制
  • 批准号:
    2344215
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    2024
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Collaborative Research: EAGER: Designing Nanomaterials to Reveal the Mechanism of Single Nanoparticle Photoemission Intermittency
合作研究:EAGER:设计纳米材料揭示单纳米粒子光电发射间歇性机制
  • 批准号:
    2345581
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    2024
  • 资助金额:
    $ 18.31万
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    Standard Grant
Collaborative Research: EAGER: Designing Nanomaterials to Reveal the Mechanism of Single Nanoparticle Photoemission Intermittency
合作研究:EAGER:设计纳米材料揭示单纳米粒子光电发射间歇性机制
  • 批准号:
    2345582
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    2024
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    $ 18.31万
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Collaborative Research: EAGER: Designing Nanomaterials to Reveal the Mechanism of Single Nanoparticle Photoemission Intermittency
合作研究:EAGER:设计纳米材料揭示单纳米粒子光电发射间歇性机制
  • 批准号:
    2345583
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Collaborative Research: EAGER: The next crisis for coral reefs is how to study vanishing coral species; AUVs equipped with AI may be the only tool for the job
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  • 批准号:
    2333604
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Collaborative Research: EAGER: Energy for persistent sensing of carbon dioxide under near shore waves.
合作研究:EAGER:近岸波浪下持续感知二氧化碳的能量。
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    $ 18.31万
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    2333603
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    $ 18.31万
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EAGER/Collaborative Research: An LLM-Powered Framework for G-Code Comprehension and Retrieval
EAGER/协作研究:LLM 支持的 G 代码理解和检索框架
  • 批准号:
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