Capturing highly dynamic beasts: Integrative characterisation of dynamic viral complexes using cryo-EM, NMR, MD, and molecular virology

该项目的目标是了解丙型肝炎病毒（HCV）复制机制的结构和动力学。这是一个巨大的结构挑战，因为它涉及到几种具有挑战性的蛋白质和RNA。各种蛋白质结构域（膜相关的/细胞质的，结构化的/无序的）的独特结构特征，加上它们的高度动态性质，都为表征该复合体带来了巨大的结构挑战。该学生将通过结合核磁共振波谱（NMR）、冷冻电子显微镜（cryo-EM）和分子动力学模拟（MD）等多种方法，以及细胞内病毒学分析，阐明HCV中RNA复制的结构细节。

The goal of this project is to understand the structure and dynamics of the replicationmachinery in hepatitis C virus (HCV). This is an enormous structural challenge as itinvolves several challenging proteins and RNA. The distinct structural features ofvarious protein domains (membrane-associated/cytosolic, structured/disordered),coupled with their highly dynamic nature, all contribute to the enormous structuralchallenge of characterising this complex. The student will elucidate the structuraldetails of RNA replication in HCV by bringing together diverse approaches such asNuclear Magnetic Resonance spectroscopy (NMR), cryo-Electron Microscopy (cryo-EM),and Molecular Dynamics simulations (MD), with in-cell virology assays.