Responsive Vesicles from Recombinant Oleosin

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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.