Professor Peter Stockley

Profile

My laboratory has recently made a major discovery concerning the self-assembly of single-stranded, positive-sense RNA viruses. These comprise very many major pathogens including those infecting humans and for which there are no current anti-viral drugs or vaccines. In a ground breaking series of papers we have overturned the existing paradigm that invoked simple charge neutralisation between negatively charged RNA and positively charge coat proteins (CPs) as the only interaction between assembling molecules. Instead it appears that such ssRNA genomes encode a self-assembly instruction manual as well as the genetic information for viral gene products. This manual is written in the form of multiple, dispersed and sequence degenerate RNA sequence motifs/secondary structures that each have affinity for their cognate CPs. These sequence-specific contacts act co-operatively to ensure faithful virions assembly in the complex milieu of the cell. This mechanism cam be studied in vitro using very dilute samples that are dye-labelled and assayed by single molecule spectroscopy. We have shown that a similar mechanism drives assembly in bacterial, plant, animal and human viruses, including the para-retrovirus Hepatitis B Virus (HBV). The latter forms its nucleocapsid initially around a single-stranded pgRNA form of its normally DNA genome. In every system where we have sufficient data to analyse it appears that the PS-CP contacts are evolutionarily conserved, i.e. they represnt a stable and novel anti-viral drug target. We have used this insight to isolate many small molecules that inhibit HBV in cell and organoid cultures more effectively than the currently used clinical drugs. This has important consequences for the estimated 400 million chronic carriers of the virus, which is the biggest cause of liver cancer worldwide. Current work focusses on understanding this fundamental mechanism in additional human pathogens such as the emerging alphaviruses and more established picornviruses. Our approach is highly interdisciplinary combining state of the art biochemical, structural and biophysical assays with traditional virology. We collaborate extensively with the theory and mathematical modelling group led by Prof Reidun Twarock at the University of York.

I studied Chemistry at Imperial College, London, before completing my PhD on Chromatin Structure in Prof. Dame Jean Thomas' laboratory in Cambridge. I subsequently worked with Prof. Steve Harrison at Harvard on the mechanisms of virus assembly before joining the staff in Leeds in 1986. Head of Department Genetics (1993-97); Deputy Director Astbury Centre for Structural Molecular Biology (1997- 2001) and then Director (2001-08); Director Interdisciplinary Institute for Bionanosciences (2002-08).

Research interests

Protein-nucleic acid interactions, genetic regulatory mechanisms, virus assembly and infection mechanisms in ssRNA virions.

• Live cell imaging capability for research on pathogenic viruses
• Mass spectrometry infrastructure for in-cell structural biology
• State of the art electron detection for cyoEM at the Astbury Biostructure Laboratories
• Structural & Functional Investigations Of A Murderous Enzyme in a Native-like Context

Qualifications

• BSc, London; PhD 1980, Cambridge.

Student education

Protein-nucleic acid interactions, eukaryotic gene expression, Virus assembly, RNA aptamers as amyloid and virus inhibitors, bionanotechnology

• Analysing transcription of chromatin templates
  Keywords: Transcription, recombinant protein purification, surface plasmon resonance
  (Laboratory)
• Biochemical dissection of transcriptional initiation
  (Laboratory)
• From RNA-protein interactions to virsu assembly
  (Laboratory)
• Protein-nucleic acid interactions, eukaryotic gene expression, Virus assembly, RNA aptamers as amyloid and virus inhibitors, bionanotechnology

Studentship information

• FindaPhD Project details:
  • Project 24367

See also:

• Faculty Graduate School

Research groups and institutes

• Structural Biology