Methamphetamine and HIV-1 Infection: Targeted Nanoparticles for Gene Silencing.

描述（由申请人提供）：收到K 01奖将允许申请人成功地过渡到一个独立的调查员，通过在快速发展的纳米技术领域进行进一步的研究，为获得新知识和技术技能提供受保护的时间。该应用程序的目标是通过将纳米技术与药物滥用在HIV-1感染中的作用研究相结合来弥合2个科学学科。后者是申请人获得由国家研究服务奖资助的博士后研究金的基础。纳米技术方面的额外培训将大大有助于申请人扩大其研究方向，将这种新的专门知识应用于开发控制与药物滥用有关的HIV-1感染的创新方法。在国际知名的纳米材料专家Paras Prasad博士的赞助下，并在她的共同赞助人Stanley Schwartz博士的指导下，申请人将接受将纳米技术应用于生物医学应用的教学和实验室培训。生物共轭纳米粒子具有很大的潜力，在单细胞水平上使用高分辨率成像研究细胞内过程。本提案将研究有机改性二氧化硅（ORMOSIL）纳米颗粒作为平台递送靶向与HIV-1感染相关的特定基因（半乳糖凝集素-1、蛋白质二硫键异构酶、硫氧还蛋白和过氧化物酶）的小干扰（siRNA）的有效性，申请人已证明HIV-1感染的表达受甲基苯丙胺调节。ORMOSIL纳米颗粒的惰性和无毒性使其成为生物医学和临床应用的有前途的材料。跨学科的环境，涉及基础科学（化学）和临床（医学）部门，支持这个项目是独一无二的最先进的设施。布法罗总医院医学系的研究实验室位于布法罗-尼亚加拉医学院，包括生物信息学和生命科学卓越中心以及罗斯韦尔公园癌症研究所。她还将利用布法罗大学主校区的激光、光子学和生物光子学研究所的设施。申请人的职业目标是成为一名独立资助的学术科学家，指导自己的研究实验室。通过连接纳米技术、成瘾研究和逆转录病毒学领域，这些研究可能会产生一种创新的、强大的新方法，为药物滥用和HIV-1感染等严重的公共卫生问题提供进一步的见解和新的干预措施。

DESCRIPTION (provided by applicant): Receipt of a K01 award will allow the applicant to successfully transition into an independent investigator by providing protected time for the acquistion of new knowledge and technical skills by undertaking further research in the rapidly advancing field of nanotechnology. The objective of this application is to bridge 2 scientific disciplines by integrating nanotechnology with research on the role of drug abuse in HIV-1 infections. The latter was the basis for the applicant's post-doctoral fellowship funded by a National Research Service Award. Additional training in nanotechnology will significantly assist the applicant to expand her research direction by applying this new expertise to the development of innovative methods to control HIV-1 infections associated with drug abuse. Under the sponsorship of Dr. Paras Prasad, an internationally known expert in nanomaterials, and with guidance from her co-sponsor Dr. Stanley Schwartz, known for his research in drugs of abuse and HIV-1 infections, the applicant will receive didactic and laboratory training in applying nanotechnology to biomedical applications. Bioconjugated nanoparticles have great potential for studying intracellular processes at the single-cell level using high-resolution imaging. This proposal will investigate the effectiveness of organically modified silica (ORMOSIL) nanoparticles as a platform to deliver small interfering (siRNA) targeted to specific genes (galectin-1, protein disulfide isomerase, thioredoxin and peroxiredoxin) relevant to HIV-1 infections whose expression has been shown by the applicant to be modulated by methamphetamine. The inertness and non-toxicity of ORMOSIL nanoparticles render them promising materials for biomedical and clinical applications. The interdisciplinary environment, involving both basic science (Chemistry) and clinical (Medicine) departments, supporting this project is unique with state of the art facilities. The research laboratories of the Department of Medicine in the Buffalo General Hospital are on the Buffalo-Niagara Medical Campus including the Center of Excellence in Bioinformatics and Life Sciences and the Roswell Park Cancer Institute. She also will utilize the facilities of the Institute for Lasers, Photonics and Biophotonics on the main campus of the University at Buffalo. The applicant's career goals are to become an independently funded, academic scientist, directing her own research laboratory. By bridging the fields of nanotechnology, addiction research, and retrovirology, these studies may yield an innovative and powerful, new methodology providing further insight into and new interventions for the serious public health issues of drug abuse and HIV-1 infections.