Responsive Vesicles from Recombinant Oleosin

该奖项由宾夕法尼亚大学材料研究部的生物材料计划授予，用于开发具有特定基序的囊泡以与细胞受体结合，开发在特定pH值下分解的囊泡，以及掺入蛋白酶可切割结构域以允许可编程释放。囊泡是由双层膜包围的水溶液的球形隔室，可用于药物递送、成像和生物催化。本计画将利用重组生物技术的工具，从两亲性蛋白质基油质蛋白制备囊泡。通过重组方法的合成将通过掺入精确的氨基酸序列来产生具有设计者功能的单分子材料。油体蛋白和许多由氨基酸截短或取代引起的突变体可以在E.大肠杆菌中的表达量较高。根据分子的精确结构和溶剂条件，有几种变体可以形成囊泡。有了这个奖励，研究者将通过进一步改变油质蛋白来制备响应性囊泡。在该项目中进行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，旨在鼓励代表性不足的群体和来自高成就学校的学生体验实验室研究。囊泡是一种被膜包围的水溶液袋，是一种特别有用的材料，可以装载药物和成像剂。虽然囊泡通常由脂质制成，但研究正在进行中，以扩大可以制造具有设计师功能的囊泡的材料的调色板。本计画是利用生物技术方法，从天然植物蛋白油质蛋白制备生物相容性囊泡。通过这种方法，每个分子都是相同的，并且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，将制备油质蛋白和构建囊泡的变体，这些变体将响应于pH值的变化而分解，这对于细胞内的药物递送或响应于蛋白酶，以制造肿瘤特异性药物递送载体是有用的。这项工作将由研究生和高中生进行，旨在鼓励代表性不足的群体参与科学，并让高成就的学生对科学和技术职业更感兴趣。

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.