◼ Research Field
  - Infectious disease research, virology

◼ Required Research Field of Study
  - Virology

◼ Description of Research Activities During the Program
  - Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in infants and young children worldwide and remains a major clinical challenge for the elderly and immunocompromised. While vaccines and monoclonal antibodies have recently expanded preventive options, our understanding of host-intrinsic factors that determine disease severity is still incomplete. In particular, human genetic variation affecting innate antiviral immunity is emerging as a key determinant of severe RSV outcomes.

This project aims to identify and mechanistically dissect genetic risk factors that compromise antiviral defense against RSV. Building on our recent genome-wide CRISPR/Cas9-based survival screen, we have identified critical host genes that modulate RSV infection at the cellular level. Using RSV reporter viruses, live-cell imaging, and interferon-responsive reporter systems, we demonstrated that tyrosine kinase 2 (TYK2), a central component of type I interferon signaling, plays a pivotal role in restricting RSV replication. Loss or functional impairment of TYK2 leads to attenuated antiviral signaling and enhanced viral replication in vitro.

Extending these findings, we now focus on coding TYK2 variants identified in human populations, particularly in children with severe RSV disease. These naturally occurring variants provide a unique opportunity to link human genetics with viral pathogenesis. Loss-of-function mutations and hypomorphic alleles will be functionally characterized to uncover how specific molecular defects weaken interferon-mediated antiviral responses. A broad spectrum of state-of-the-art cell biological, molecular, and virological techniques will be employed to address these questions.

By integrating human genetic data with mechanistic infection biology, this project seeks to uncover fundamental principles of RSV host defense. It offers an exciting and intellectually stimulating research environment for international Master’s students eager to gain hands-on experience at the interface of virology, immunology, and functional genomics.

◼ Research Equipment or Software to be Used
  - FACS, next generation sequencing, live cell imaging, confocal microscopy, etc.

◼ Website
  - https://twincore.de/labs/pietschmann-lab