Infection Medicine

Dr Gracjan Michlewski awarded new BBSRC grant

Dr Gracjan Michlewski has been awarded a grant worth £510,000 to investigate the role of novel RNA-binding protein TRIM25 in viral nucleic acids sensing and signalling.

Dr Gracjan Michlewski of Infection Medicine is leading a £510k project, funded by the UK Government’s Biotechnology and Biological Sciences Research Council, which aims to investigate the role of novel RNA-binding protein TRIM25 in viral nucleic acids sensing and signalling.

TRIM25 inhibits IAV infection by directly binding to viral RNAs and mRNAs through yet uncharacterised molecular mechanism.

Investigating the role of novel RNA-binding protein TRIM25 in viral nucleic acids sensing and signalling

E3 ubiquitin ligase TRIM25 is emerging as a key factor in the innate immune response to RNA viruses, including influenza A virus (IAV), HIV, SARS, dengue virus and many others. We have recently discovered that TRIM25 possesses RNA-binding activity. Despite the essential involvement of TRIM25 in viral RNA-induced innate immune pathways, its RNA-binding functions are still poorly understood. In this project we will study the role of RNA-binding activity of TRIM25 in innate immune pathways in the context of IAV infections.

The importance of the project

RNA viruses are an important class of pathogen that continue to cause devastating epidemics in the 21st century. Taking IAV as an exemplar, it threatens periodic pandemics, kills 250,000 to 500,000 people annually even in epidemic phases, generating a significant socioeconomic burden. The impact of IAV infections on livestock animals is equally tremendous. During a 2005 bird flu outbreak the total economic losses in South East Asia alone were calculated at around $10 billion. However, we still do not know all of the molecular mechanisms of key host proteins that sense and restrict human and animal IAV infections.