Identification of essential virus-host cell interactions which are required for virus replication or transformation.
We are utilising a range of cutting-edge transcriptomic and quantitative proteomic approaches to globally identify how viral proteins affect the cellular environment. These interactions can then be verified using biochemical and con-focal imaging techniques. This is helping to identify essential virus-host cell interactions which we can target by novel antiviral strategies to inhibit virus replication and transformation. We are particularly interested in virus-host cell interactions which:
Regulate reactivation in Kaposi's sarcoma associated herpesvirus
Regulate virus RNA processing
Immune evasion strategies employed by oncogenic viruses
Virus-host cell interactions required for the aggressive metastatic potential of some virus-induced cancers
Structural-based rational drug design approaches to inhibit oncogenic viruses
To date, there are limited antiviral strategies for oncogenic viruses. Although vaccines have been developed for a few of these viruses, these are not available for all the 7 oncogenic viruses, incluing KSHV and MCPyV. Therefore novel antiviral straetgies are required to combat these important human pathogens. Upon identification of essential virus-host cell interactions using transcriptomic and quantitative proteomic approaches, we utilise a structural-based rational drug design approach to molecular model and design small molecules to inhibit these interactions. Virtual high-throughput screening campaigns are conducted from a large libraries of commercially available compounds. Docking routines and ligand-similarity searches are utilised to design compounds which have the potential to inhibit these essential virus-host cel interactions. Once the virtual high-throughput screening campaign has been performed selected compounds are then assessed in virus-based assays for antiviral activity.
Research is currently funded by BBSRC (PDRAs and PhDs), MRC (PDRA and PhDs), Worldwide Cancer Research (PDRA), Royal Society GCRF (PDRA), Rosetrees Trust (PhD) and Wellcome Trust (PhD).
A list of recent publications from the laboratory are listed at Recent publications
Other projects include:
Host-virus interactions in KSHV-related malignancies: evaluating the role of STIP/HOP as a therapeutic target, 2023-2028, Medical Reserach Council (MRC), £333,536
Royal proteins: role in KSHV RNA processing to novel antiviral approaches, 2023-2026, Medical Reserach Council (MRC), £1,009,794
Targeting transfer RNA-derived fragments during KSHV infection, 2021-2024, Medical Reserach Council (MRC), £824,113
Virus manipulation of host non-coding RNA regulatory networks, 2020-2023, Biotechnology and Biological Sciences Research Council (BBSRC), £791,347