Developing Individual Particle Electron Tomography (IPET) for the Study of Protein Dynamics via the Structure Determination of a Single Protein

Proteins are one of the most fundamental building blocks of life, involved in virtually all cell functions and biological processes; yet, due to their size and constantly fluctuating structure, they remain one of the least understood. The research objective of this laboratory is to develop a technique for the direct determination of the high-resolution structure (better than 1nm) of a single protein (an individual object, no average) using intermediate resolution imaging (1-2nm). The dynamic personalities and structural heterogeneity of proteins are essential for their proper functions, but structural determination of dynamic and heterogeneous proteins is very challenging by conventional approaches. X-ray, NMR, and single-particle Electron Microscopy (EM) techniques all require the averaging of thousands to millions of different proteins without known if these proteins share an identical same structure. The averaging of different protein structures will result missing leading in structure and will lose the information about protein naturally fluctuation. This lab utilizes a high-resolution structural determination method, named individual particle electron tomography (IPET), to determine an individual protein structure near an intermediate resolution (1-2 nm). We continue to develop this approach by optimizing through empirical and computational methods to achieve high-resolution structures of single proteins. This knowledge will become invaluable for addressing the most important questions in both biology and soft-materials. For more details on what The Ren Group is doing, look at our Research page.