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

纳米技术使许多产品得到改进。这些包括电子显示器，计算机存储芯片，锂离子电池，增白剂和更强的碳纤维，仅举几例。近年来，人类与这些颗粒的接触急剧增加。令人惊讶的是，人类细胞能够吸收并处理这些颗粒。该项目将研究这些类型的颗粒对人体细胞代谢的影响。该项目还将与当地高中生和高中教师合作，其中许多人服务于代表性不足的少数民族（URM）人口。这样做将加强科学、技术、工程和数学（STEM）基础设施，鼓励URM学生更多地参与STEM职业，并支持扩大生物制造领域的高科技劳动力。多种工程纳米材料（enm）的加工途径演变为回收和降解细胞内纳米材料。有证据表明，自噬溶酶体（AL）系统的激活是对ENM摄取的适应性反应。我们假设AL系统通过类似于天然纳米材料激活的分子机制对enm作出反应。受天然纳米材料规律的启发，该项目将1)生成合成纳米颗粒和基因编码纳米结构，模拟天然纳米颗粒及其自噬机制；2)通过监测溶酶体的生物发生、功能和完整性来阐明这些新型仿生纳米材料对溶酶体系统的影响；3)利用专门设计的体外模型系统来评估enm对该途径每一步的影响，表征对这些仿生纳米材料的反应。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.