Responsive Vesicles from Recombinant Oleosin

来自重组油质蛋白的响应性囊泡

• 批准号: 1309556
• 负责人: Daniel Hammer
• 金额: $ 42万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1309556&HistoricalAwards=false
• 关键词: Responsive; Vesicles; Recombinant; Oleosin

This award by the Biomaterials program in the Division of Materials Research to University of Pennsylvania is for the development of vesicles endowed with specific motifs to bind with cell receptors, the development of vesicles that disassemble at specific pH's, and for the incorporation of protease cleavable domains to allow programmable release. Vesicles, spherical compartments of aqueous solution surrounded by a bilayer membrane, can be used for drug delivery, imaging, and biocatalysis. With this project, vesicles will be prepared from amphiphilic protein based oleosin using the tools of recombinant biotechnology. Synthesis by recombinant methods would produce monomolecular materials with designer functionality through the incorporation of precise amino acid sequences. Oleosin, and numerous mutants resulting from either truncation or substitution of amino acids, can be expressed in E. coli with high yields. Several variants make vesicles, depending on the precise architecture of the molecules and solvent conditions. With this award, the investigator will prepare responsive vesicles by further alterations of oleosin. Students doing research in this project will be trained in multidisciplinary areas. This work will be conducted by graduate students and by high school students in a unique outreach program designed to encourage both underrepresented groups and students from high achieving schools to experience laboratory research.There is an increasing need to make biocompatible materials that can carry bioactive agents. A vesicle, a bag of aqueous solution surrounded by a membrane, is a particularly useful material which can be loaded with drugs and imaging agents. Although vesicles are often made from lipids, research is ongoing to expand the palette of materials that can make vesicles with designer functionality. This project is to prepare biocompatible vesicles from a naturally occurring plant protein, oleosin, which the investigator has demonstrated using the biotechnology methods. With this approach, every molecule would be identical, and embedding specific functionality could be straight forward through simply changing the gene. With this project, variants of oleosin and construct vesicles will be prepared that will fall apart in response to changes in pH, which are useful for drug delivery inside of a cell, or in response to proteases, to make tumors-specific drug delivery vehicles. This work will be conducted by graduate students and by high school students, in an outreach program designed to both encourage underrepresented groups to participate in science and to get high achieving students more interested in careers in science and technology.

这一奖项由宾夕法尼亚大学材料研究部的生物材料计划授予，以表彰具有与细胞受体结合的特定基序的囊泡的开发，在特定pH下分解的囊泡的开发，以及加入蛋白酶可切割结构域以允许可编程释放的奖项。囊泡是由双层膜包围的水溶液的球形隔间，可用于药物输送、成像和生物催化。在这个项目中，将使用重组生物技术工具从两亲性蛋白质基油球蛋白中制备囊泡。通过重组方法的合成将通过加入精确的氨基酸序列来产生具有设计功能的单分子材料。油球蛋白和许多因氨基酸截断或取代而产生的突变体可以在大肠杆菌中高产率地表达。根据分子的精确结构和溶剂条件，有几种变体可以产生囊泡。获得这一奖项后，研究人员将通过进一步改变油球蛋白来制备响应性囊泡。在这个项目中从事研究的学生将接受多学科领域的培训。这项工作将由研究生和高中生在一个独特的推广计划中进行，该计划旨在鼓励代表不足的群体和成绩优异的学校的学生体验实验室研究。人们越来越需要制造能够携带生物活性物质的生物兼容材料。囊泡是一种特别有用的材料，它是一种特别有用的材料，可以装载药物和显像剂。虽然囊泡通常是由脂质制成的，但研究正在进行中，以扩大材料的调色板，可以制造具有设计者功能的囊泡。这个项目是从一种自然产生的植物蛋白油球蛋白中制备生物相容的囊泡，研究人员已经使用生物技术方法证明了这一点。使用这种方法，每个分子都是相同的，通过简单地改变基因就可以直接嵌入特定的功能。通过该项目，将制备油球蛋白和构建囊泡的变体，这些变体将随着pH的变化而崩解，pH变化对细胞内的药物输送有用，或者对蛋白酶的反应，以制造肿瘤特异性药物输送载体。这项工作将由研究生和高中生进行，这项推广计划旨在鼓励代表性不足的群体参与科学，并让成绩优异的学生对科学和技术职业更感兴趣。