Engineering nanoparticles and nanostructures with precise and tunable modalities of interaction with the autophagy-lysosome system

William Marsh Rice University, Houston TX

Investigators

Abstract

Nanotechnology has led to improvements in many products. These include electronic displays, computer memory chips, lithium ion batteries, whiteners, and stronger carbon fibers, to name a few. Human exposure to these particles has skyrocketed in recent years. Surprisingly, human cells are able to take up and process these particles. This project will investigate the effect that these types of particles have on human cell metabolism. The project will also engage with local area high school students, and HS teachers, many who serve underrepresented minority (URM) populations. Doing so will strengthen the science, technology, engineering and mathematics (STEM) infrastructure, encourage greater participation in STEM careers by URM students, and support the expansion of a high-tech workforce in biomanufacturing. A variety of engineered nanomaterials (ENMs) are processed by pathways evolved to recycle and degrade intracellular nano-sized materials. Evidence points to the activation of the autophagy-lysosome (AL) system as an adaptive response to ENM uptake. We hypothesize that the AL system responds to ENMs through molecular mechanisms similar to those activated in response to natural nanomaterials. Inspired by the rules of naturally occurring nanomaterials, this project will 1) generate synthetic nanoparticles and genetically encoded nanostructures that mimic natural nanosized particles and their autophagy-evoking mechanisms; 2) elucidate the impact of these novel bio-inspired nanomaterials on the lysosomal system by monitoring lysosomal biogenesis, function, and integrity; and 3) characterize the response to these bio-inspired nanomaterials by utilizing in vitro model systems specially designed to evaluate the impact of ENMs on every step of this pathway. 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.