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.