CAREER: Engineering cellular clearance pathways using nanoparticles

1254318隔离纳米粒子现在被设计用于各种重要的应用，从诊断和治疗到能源生产和材料。许多不同大小、形状和组成的纳米颗粒通过内吞作用进入细胞，激活细胞清除机制，特别是自噬，这是消除细胞废物和外来物质的主要分解代谢途径。有趣的是，受损或低效的自噬活动与细胞废物物质的积累和许多癌症、衰老和代谢疾病的发展有关。该项目团队最近开发了一套分析工具来量化细胞清除能力和细胞模型系统来测量细胞废物的积累。拟议项目的总体研究目标是利用纳米颗粒设计细胞清除途径。为了实现这一目标，研究小组将确定纳米颗粒，以增强对有毒细胞废物的清除，并将利用这些纳米颗粒来研究参与自噬调节的分子机制。这项研究将为开发新的治疗策略奠定基础，以治疗与自噬功能障碍相关的病理状况，从衰老、代谢疾病到癌症。该研究项目将为教育和培训平台的发展提供基础，最终的教育目标是使对生物分子工程感兴趣的学生群体多样化，并增加STEM学科中代表性不足的群体（特别是女孩和妇女）的保留率。为此，该项目整合了与高中生、本科生、研究生和教师相关的教育目标。该职业奖由生物基础设施部（DBI）通过生物研究仪器开发（IDBR）项目和化学、生物工程、环境和运输系统部（CBET）共同资助。

1254318SegatoriNanoparticles are now being engineered for a variety of important applications, ranging form diagnostics and therapeutics to energy production and materials. A number of nanoparticles of different size, shape and composition enter the cell through endocytosis and activate cellular clearance mechanisms and, particularly, autophagy, which is the main catabolic pathway that eliminates cellular waste and foreign material. Interestingly, impaired or inefficient autophagic activity is linked to accumulation of cellular waste material and development of a number of cancers, ageing and metabolic diseases. The project team recently developed a set of analytical tools to quantify the cellular clearance capacity and cell model systems to measure the accumulation of cellular waste. The overall research goal of the proposed project is to engineer the cellular clearance pathway using nanoparticles. To achieve this goal, the research team will identify nanoparticles that enhance clearance of toxic cellular waste material and will use these nanoparticles to investigate the molecular mechanism involved in regulation of autophagy. This study will lay the groundwork for developing novel therapeutic strategies to treat pathologic conditions associated with autophagy dysfunction, ranging from ageing and metabolic diseases to cancer. This research project will provide the basis for the development of educational and training platforms, with the ultimate educational goal of diversifying the pool of students interested in biomolecular engineering and of increasing the retention of underrepresented groups - particularly girls and women - in STEM disciplines. To this end, the project integrates educational objectives relevant to high school students, undergraduate students, graduate students, and faculty.This CAREER award is co-funded by the Division of Biological Infrastructure (DBI) through the Instrument Development for Biological Research (IDBR) program, and by the Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET).