Research Initiation Award: Nano-vehicles for delivery of small molecules to mitochondria in Saccharomyces cerevisiae model

Albany State University, Albany GA

Investigators

Abstract

Non-technical Abstract: Mitochondria are important cellular organelles that play a crucial role in cellular metabolism and provide energy for the survival of the cell. The self-destruction of the cell is also a process initiated by the mitochondria. Over the years, researchers try to engineer mitochondria to modulate the survival and efficiency of cells. Some natural small molecules and synthetic chemicals are currently available to modulate mitochondrial functions. However, their applications are restricted because of bioavailability and biotransformation issues. This project develops nanosized particles capable of safely and efficiently delivering small molecules to mitochondria in Baker’s yeast cells. The observations can be extrapolated to cells of higher organisms, including plants, animals, and humans. The principal investigator and the undergraduate students from the minority institution working on this project have the opportunity to expand their potential in interdisciplinary areas of biology while contributing to the biomanufacturing and biomedical sectors. Technical Abstract: Mitochondria are unique sub-cellular organelles in eukaryotic cells and mediate various cellular and metabolic processes. Some natural compounds like quercetin, resveratrol, and curcumin are identified to have positive modulation effects on mitochondria by their ability to alter the production of reactive oxygen, modulating gene expression, thereby changing mitochondrial dynamics, which influence the physiology and survivability of cells. But one of the major problems in mainstreaming the use of these small molecules is their bioavailability and metabolic transformation. The current project aims to develop resveratrol encapsulated nanoparticles capable of transgressing the cell boundaries and reaching the mitochondria. To address this, the current project (1) develops resveratrol encapsulated nano-vehicles and evaluates their stability using phytochemical and chromatographic tools, (2) studies the mechanisms of endocytosis, intra-cellular transport of nano-vehicles, and mitochondrial delivery of small molecules by employing genomics and proteomic analysis in Baker’s yeast, Saccharomyces cerevisiae, (3) demonstrates efficacy and safety of nano-vehicles using cell biology and microscopy techniques, and (4) provides research-based training to undergraduate students in areas of interdisciplinary research methods, nano-particle preparation and analysis, cell biology, molecular biology, and mitochondria analysis. The nano-vehicle developed has the potential applications in several biological, biomanufacturing and biomedical fields. 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.