Nanomedicine Center for Protein Deposition Diseases(RMI)

UNMC纳米药物开发中心的主题是蛋白质错误折叠现象。蛋白质的错误折叠会导致不同形态的蛋白质纳米颗粒的自发形成，特别是纳米纤维。蛋白质的错误折叠和聚集是许多重要的人类健康问题背后的共同线索。对导致各种神经退行性疾病中蛋白质错误折叠和自我聚集的分子过程的基本了解将提供关键信息，以帮助确定控制这些过程的适当治疗途径。尽管蛋白质错误折叠及其自组装成聚集体至关重要，但目前对这些过程背后的分子机制知之甚少。导致蛋白质聚集的因素有 人们对蛋白质纳米颗粒的形成知之甚少，更不用说不同形态的蛋白质纳米颗粒的形成了，首先是纳米孔。目前还不清楚为什么即使是同一种蛋白质的聚集有时也会导致纤维状、孔状物和无定形聚集，以及如何防止聚集。了解聚集的分子机制可能具有巨大的实际意义。它将有助于合理设计旨在抑制和控制蛋白质聚集的方法，模拟和操纵细胞内的聚集过程。控制这些过程的能力提高了药物输送的效率，最终将导致预防和治疗蛋白质沉积疾病。为了实现这些目标，我们将开发基于纳米技术的新方法来观察和测量 单个分子之间的相互作用，在体外操纵相互作用的分子，将开发出控制细胞内蛋白质聚集过程的实用解决方案。我们的最终目标是开发纳米医学方法来修复有缺陷的机器或用人造纳米系统取代它们。我们组建了一个由12名研究人员组成的多学科团队，他们在纳米生物学、成像、光谱学、单分子生物物理学、蛋白质组学、药物输送和医学方面拥有广泛的专业知识。

The main theme of the UNMC Nanomedicine Development Center is the protein misfolding phenomenon. Protein misfolding leads to spontaneous formation of protein nanoparticles of different morphologies, nanofibrils in particular. Misfolding and aggregation of proteins is a common thread behind a number of important human health problems. A fundamental understanding of molecular processes leading to misfolding and self-aggregation of proteins involved in various neurodegenerative diseases will provide critical information to help identify appropriate therapeutic routes to control these processes. Despite crucial importance of the protein misfolding and its self-assembly into aggregates, very little is currently known about the molecular mechanism underlying these processes. Factors that lead to protein aggregation are poorly understood not to mention the formation of the protein nanoparticles with different morphologies, the nanopores in the first place. It is unclear why aggregation even of the same protein sometimes leads to fibrillar, pore-like and amorphous aggregates and how aggregation may be prevented. Understanding the molecular mechanism of aggregation could have tremendous practical importance. It will facilitate the rational design of approaches aimed at inhibiting and controlling protein aggregation, modeling and manipulating the aggregation process within cells. The ability to control these processes increases the efficiency of drugs delivery, and eventually will lead to prevention and cure of protein deposition diseases. To achieve these goals we will develop novel nanotechnology based approaches for observation and measuring the interaction between individual molecules, manipulating with interacting molecules in vitro and will develop practical solutions for controlling protein aggregation process within cells. Our ultimate goal is the development of nanomedicine approaches to repair defective machines or to replace them with artificial nanosystems. We assembled a multidisciplinary team of 12 investigators with broad expertise in nanobiology, imaging, spectroscopy, single molecule biophysics, proteomics, drug delivery and medicine.