GRK 2887: VISualization and structure in virus infectION (VISION)

Severe illness caused by viral pathogens constitutes a constant threat to the human society, either as acute epidemics with dramatic consequences or as chronic viral infections in individuals with an increased susceptibility, e.g., due to a compromised immune system. The development of efficient antiviral intervention strategies can be reduced to two steps: 1) a profound understanding of an essential process within the viral life cycle and 2) the capitalization on this knowledge to devise novel antiviral strategies. In this context, basic virology research has laid the grounds for a number of successful antiviral campaigns and structural studies and imaging have been a major pillar in understanding basic molecular principles occurring during viral infection. Historically, imaging-based analyses revealed molecular details at just one specific resolution level by applying classical techniques like fluorescence microscopy (lower resolution), electron microscopy (EM, intermediate resolution), X-ray crystallography or nuclear magnetic resonance (NMR, both at atomic resolution). Recent virology research has revealed the urgent need to extend our understanding to the mechanistic level, i.e., how viral proteins and protein complexes exert their functions within the host cell. To understand virus infections mechanistically, a more dynamic analysis of viral proteins is indispensable - not only in isolated form, but also in the context of their native environment. In addition, such an extended understanding requires an integrative imaging approach, i.e., the combination of data from different methodologies across a wide resolution range from live cells to individual atoms. To address these challenges a number of additional, complementary methodologies (e.g., super-resolution fluorescence microscopy, correlative light and electron microscopy, live cell fluorescence microscopy or time-resolved crystallography) have been developed. Our focus will be to train a new generation of virologists to use cutting-edge imaging techniques thereby establishing an integrative structural virology approach to better understand the complexity of mechanisms and biology in the course of viral infections. Importantly, integration of these techniques with structural virology research requires a specific training in both structural biology and functional virology to successfully address the challenges mentioned above. We therefore propose a cross-disciplinary research training group with three key aims: 1. To instruct a new generation of scientists in how to address future challenges in virology research at the interface between virology and structural biology by applying cross-disciplinary, multi-resolution techniques. 2. To further develop integrative methods that bridge different resolution scales in virology. 3.To apply these interdisciplinary approaches to challenging virological questions that pave the way for the development of novel antiviral intervention strategies.