Protein Vesicles: Understanding Self-Assembly of Fusion Proteins into Vesicles to Engineer Structures and Biofunctional Properties

蛋白质囊泡：了解融合蛋白自组装成囊泡以设计结构和生物功能特性

• 批准号: 1709428
• 负责人: Julie Champion
• 金额: $ 39.36万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709428&HistoricalAwards=false
• 关键词: Protein; Vesicles; Understanding; Self; Assembly

Non-technical:This award supports the study and development of vesicles made from functional proteins. Vesicles are micro or nano-scale hollow containers that can be loaded with cargo and used for drug delivery, bioimaging, or as tiny bioreactors. Functional proteins can be therapeutic or perform reactions, and vesicles made from these proteins gain their function. The proposed studies are expected in developing an understanding on how the properties of the proteins and the fabrication conditions affect the size and structure of the formed vesicles so that one may control these properties for each application. To demonstrate their use, vesicles will be formed from a breast cancer binding protein and loaded with chemotherapeutic cargo and tested for their ability to kill breast cancer cells. Overall, this research will contribute to the development of protein vesicles for a variety of applications that support human health and the results will be published for public dissemination. During this work, a postdoctoral student and undergraduates will be trained in state of the art methods that integrate materials engineering and biology and they will be prepared for careers in engineering, biomaterials, or drug delivery. Additionally, this award will support activities to recruit, mentor and retain women in STEM at education levels ranging from middle school to post-doctoral, including hands-on experiments for middle school girls in the lab.Technical:This award supports the study of fusion protein self-assembly into vesicles using techniques such as light scattering and electron microscopy. The knowledge generated will be applied to fine tune vesicle properties, including size and membrane structure, through simple changes in assembly conditions. The proposed studies are expected to produce vesicles ranging from ~100 nanometer to 2 micro meter with single or double layer membranes while maintaining the functionality of proteins that form the vesicle membrane and cargo loading ability. Functional application will be demonstrated by assembling vesicles from fusion proteins containing single chain antibody fragments that bind the Her2 receptor on breast cancer cells and carry chemotherapeutic. The ability of these functional vesicles to specifically target and kill Her2+ breast cancer cells will be assessed in vitro. The results will be published for public dissemination. During this work, a postdoctoral student and undergraduates will be trained in methods including recombinant protein design and production, materials characterization, and cell culture assays. They will be mentored and prepared for careers in engineering, biomaterials, or drug delivery. Additionally, this award will support activities to recruit and retain women in STEM at education levels ranging from middle school to post-doctoral, including hands-on experiments for middle school girls in the lab.

非技术性：该奖项支持由功能蛋白质制成的囊泡的研究和开发。囊泡是微米或纳米级的中空容器，可以装载货物并用于药物输送，生物成像或作为微型生物反应器。功能性蛋白质可以是治疗性的或执行反应，并且由这些蛋白质制成的囊泡获得它们的功能。预计拟议的研究将有助于了解蛋白质的性质和制造条件如何影响所形成的囊泡的大小和结构，以便人们可以控制每种应用的这些性质。为了证明它们的用途，囊泡将由乳腺癌结合蛋白形成，并装载化疗货物，并测试它们杀死乳腺癌细胞的能力。总的来说，这项研究将有助于蛋白质囊泡的开发，用于支持人类健康的各种应用，研究结果将公布于众。在这项工作中，博士后学生和本科生将接受最先进的方法培训，将材料工程和生物学相结合，他们将为工程，生物材料或药物输送的职业生涯做好准备。此外，该奖项还将支持在STEM领域招募、指导和留住从中学到博士后的教育水平的女性的活动，包括在实验室中为中学女生进行动手实验。技术：该奖项支持使用光散射和电子显微镜等技术研究融合蛋白自组装成囊泡。所产生的知识将被应用于微调囊泡的性质，包括大小和膜结构，通过简单的改变组装条件。预计拟议的研究将产生具有单层或双层膜的约100纳米至2微米的囊泡，同时保持形成囊泡膜的蛋白质的功能和货物装载能力。功能性应用将通过从含有单链抗体片段的融合蛋白组装囊泡来证明，所述单链抗体片段结合乳腺癌细胞上的Her2受体并携带化疗剂。将在体外评估这些功能性囊泡特异性靶向和杀死Her2+乳腺癌细胞的能力。结果将公布，供公众传播。在这项工作中，博士后学生和本科生将接受包括重组蛋白设计和生产，材料表征和细胞培养测定方法的培训。他们将接受指导，并为工程，生物材料或药物输送的职业生涯做好准备。此外，该奖项将支持在从中学到博士后的教育水平上招募和留住STEM女性的活动，包括在实验室中为中学女生进行动手实验。

项目成果

Photocrosslinked, Tunable Protein Vesicles for Drug Delivery Applications

用于药物输送应用的光交联、可调蛋白囊泡

• DOI: 10.1002/adhm.202001810
• 发表时间: 2021
• 期刊: Advanced Healthcare Materials
• 影响因子: 10
• 作者: Li, Yirui;Champion, Julie A.
• 通讯作者: Champion, Julie A.

Protein Vesicles Self-Assembled from Functional Globular Proteins with Different Charge and Size

• DOI: 10.1021/acs.biomac.0c00671
• 发表时间: 2021-01-01
• 期刊: BIOMACROMOLECULES
• 影响因子: 6.2
• 作者: Dautel, Dylan R.;Champion, Julie A.
• 通讯作者: Champion, Julie A.

Understanding the Coacervate-to-Vesicle Transition of Globular Fusion Proteins to Engineer Protein Vesicle Size and Membrane Heterogeneity

• DOI: 10.1021/acs.biomac.9b00773
• 发表时间: 2019-09-01
• 期刊: BIOMACROMOLECULES
• 影响因子: 6.2
• 作者: Jang, Yeongseon;Hsieh, Ming-Chien;Champion, Julie A.
• 通讯作者: Champion, Julie A.