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James Murphy

James Murphy

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PhD - University of Leeds 2016 to Present (Wellcome Trust - Molecular Basis of Biological Mechanisms)

Research interests

Viruse Induced Specalised Ribosomes:

Historically, ribosomes have been viewed as unchanged homogeneous units with no intrinsic regulatory capacity for mRNA translation. Recent research is shifting this paradigm of ribosome function to one where ribosomes may exert a regulatory function or specificity in translational control. Emerging evidence has identified heterogeneity of ribosome composition in specific cell populations, leading to the concept of specialised ribosomes. Viruses manipulate many cellular pathways to enhance their replication, therefore we have examined whether Kaposi’s sarcoma associated herpes virus (KSHV) alters host cell ribosome composition to enhance the production of viral proteins.

Using a B cell line containing latent KSHV episomes, we have produced eight cell lines that stably express different ribosomal associated proteins containing tandem affinity purification (TAP) tags. Using TAP we have isolated precursor ribosome complexes from latent and lytically replicating KSHV infected cells. TMT-labelling coupled to LC-MS/MS was used to identify changes in the stoichiometry and composition of the precursor ribosomal complexes during lytic vs latent KSHV infection. Using a variety of molecular biology techniques, we are currently confirming these changes and detailing how they affect virus replication. We are also using cryo-EM to solve the structure of isolated precursor ribosome complexes and modeling these structures against high-detail cryo-EM ribosome maps to help further identify loss or gain of proteins from these complexes throughout KSHV infection.   

Our research will demonstrate how viruses can engineer specific specialised ribosomes that could preferentially translate viral mRNAs over host mRNAs by altering ribosome composition.      

Qualifications

  • PhD, Molecular Basis of Biological Mechanisms, University of Leeds
  • BSc, Biological Sciences, University of Leeds