Natural products are rich in biologically active (bioactive) compounds and serve as great sources for drug discovery. One of the major challenges in screening drug leads from natural products is the lack of effective tools to identify and separate the bioactive compounds. This project will develop and characterize a new magnetic separation approach based on cell membrane-encapsulated iron oxide superparticles (a cluster of nanoparticles) for the separation and identification of bioactive compounds from natural products. This method overcomes limitations of costly and time-intensive conventional approaches and the nonspecific binding problems of magnetic bead separation techniques. The new approach is also broadly applicable to many different types of transmembrane drug targets. The success of this project will advance industrial processes for identification and extraction of new drug leads from complex samples. The impact of this project will be further enhanced through student-led educational and outreach activities, including: (a) establishing a goal-oriented training mechanism and relevant course work for undergraduate researchers and (b) developing a STEM lead the way program with an emphasis on math concept building. Specific science outreach projects to be developed are Science middle school-targeted Olympiad training modules and magnetic fishing experiments for elementary school students through the "Science Party for Kids" program.
The objective of this project is to develop a new magnetic separation approach based on cell membrane-encapsulated iron oxide superparticles (CSMPs) for the identification and separation of bioactive compounds from natural products. CSMPs will feature immobilized cell membranes with fully functional receptors that allow for identification of compounds specifically binding to the transmembrane receptors. The full encapsulation of magnetic superparticles inside a cell membrane overcomes the non-specific binding problems associated with the current magnetic bead separation technology. The use of magnetic superparticles enables rapid identification and extraction of compounds targeting transmembrane proteins. The CSMP approach is also easily translated to different transmembrane protein targets, which significantly broadens the applicability of this separation technique. Toward the overall objective, the PIs will develop, characterize, and evaluate the CSMP approach using cell membranes with functional nicotinic receptors to effectively identify binding compounds both in an artificial mixture (known binders and non-binders) and cigarette smoke condensates. The technique will be further verified using cell membranes with functional transient receptor potential (TRP) channels (e.g., TRPV1) and voltage-gated sodium channels. Both types of receptors have been shown as valid targets for the development of novel analgesic drugs. The outcome of the project will be fundamental knowledge related to efficient separation of bioactive compounds from complex matrices.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
