Urs Greber

Passwords, signals and traffic in virus infections 

Viruses carry genetic information between cells and individuals. Upon entry into cells, they unfold uncharted levels of complexity in single cells, organs and individuals. This can lead to severe disease, sometimes with worldwide impact.
Research in our laboratory focuses on adenoviruses and rhinoviruses, two agents causing human respiratory disease. Human adenoviruses also elicit malignant cell transformations, and can emerge from latent stages in immune-compromised individuals, and engineered adenoviruses are used in clinical gene therapy trials. Our previous work has shown that adenoviruses employ a stepwise program for infectious entry into epithelial cells. They escape from endosomes to the cytosol, and deliver their DNA genome into the nucleus. This requires virus-induced signaling cascades, activations of membrane lytic processes, cytoskeletal tracks and molecular motors, as well as a stepwise cascade of events leading to uncoating of the viral genome.
To analyze these processes, we are using a dual approach, system-wide analyses of the infection phenotypes, and reductionist studies to elucidate the molecular mechanisms supporting the infections. We employ static and live imaging of cells and viruses and combine this with biochemical analyses and numerical models. Our overall aim is to elucidate how viruses take control over membrane and lipid functions and dynamics, cytoplasmic transport processes and metabolism to support their gene expressions, progeny formation and ultimately transmission between cells. We complement these mechanistic studies by system-wide analyses to understand how viral agents bypass the dynamic defense mechanisms of the host, and thereby establish and maintain infections.
We hope that this research will yield new insights into molecular mechanisms underlying cell functions and infection processes, and provide a basis for viral applications in clinical research and biotechnology. This may enable the design of new anti-viral agents.