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

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

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.