... understanding life in molecular detail

Prof Mark Harris

Hepatitis C virus, Chikungunya virus, Ebolavirus, RNA protein interactions, replication, assembly, antiviral development

My research seeks to understand the molecular mechanisms underpinning the replication of the important human pathogens, hepatitis C virus and Chikungunya virus. In particular we wish to understand how these viruses replicate their RNA genomes and interact with host cell proteins. We hope that this information will lead to the development of novel, much needed, therapeutics.  In a separate project we are working with colleagues in the School of Chemistry to develop novel antivirals to block Ebola virus genome replication.

Current major projects include:
  • Structure and composition of HCV and CHIKV RNA replication complexes
  • Functional studies on the HCV and CHIKV non-structural proteins
  • Structure-based drug design to develop new antivirals

Research areas:

My laboratory works on three important human viruses - hepatitis C virus (HCV), Chikungunya virus (CHIKV) and Ebolavirus (EBOV).  

Our primary aim is to understand mechanisms of virus replication and pathogenesis with a view to developing new therapeutic options.
For HCV and CHIKV we are applying similar range of technical approaches – for example proteomic analysis to determine the interactomes of key viral non-structural proteins (HCV NS5A and CHIKV nsP3).  A major focus is the role of phosphorylation in regulating the interactome and the different functions of these proteins.   We are following our mass spectrometric analysis of sites of phosphorylation in NS5A with a functional analysis of the role of this post-translational modification in virus replication. 

We are using imaging techniques to probe the multiprotein complexes that replicate the viral genome.  These include genetically tagging these viruses to enable either high resolution EM or fluorescent imaging, in collaboration with Michelle Peckham (Leeds) we are utilising both super-resolution and confocal microscopy, the latter located within a category III containment facility – a unique resource within the UK for the study of HCV. 

In collaboration with Colin Fishwick (Leeds) we are applying structure-based drug design methodology to viral proteins.  In particular we have established a new research project to use this approach to develop small molecule inhibitors of EBOV replication which we hope that these may form the basis for a novel future therapeutic approach.  This project utilises a mini-genome system which does not require growth of this highly pathogenic virus, but recapitulates key events in the virus lifecycle. An alternative approach to development of antivirals comes from a collaboration with colleagues in Brazil (Carol Jardim and Paula Rahal) to exploit the unique flora of that country for potential pharmacologically active compounds.  Recent publications have exemplified both of these antiviral strategies.  

Recently, homologues of HCV have been identified in other species, the closest relative is the non-primate hepacivirus (NPHV) identified in both dogs and horses.  We have begun a programme of work on this virus, both as a model system to study HCV but also for comparative studies – although closely genetically related to HCV, NPHV does not appear to cause disease and this difference may shed light on some of the pathogenic mechanisms specific to HCV.

Detailed research programme                  Close ▲

Professor of Virology
PhD (Glasgow)

MRC Fellowship (Glasgow) 1994-1997
Lecturer (Leeds) 1997-2001
Senior Lecturer (Leeds) 2001-2005
Reader (Leeds) 2005-2006

Garstang 8.59
School of Molecular and Cellular Biology
0113 343 5632

Selected Publications

  1. Mankouri J, Walter C, Stewart H, Bentham M, Park WS, Heo WD, Fukuda M, Griffin SD and Harris M. Release of infectious hepatitis C virus from Huh7 cells occurs via a trans-Golgi network to endosome pathway independent of very-low-density lipoprotein secretion. J Virol. in press doi:10.1128/JVI.00826-16

  2. Stewart H, Bingham RJ, White SJ, Dykeman EC, Zothner C, Tuplin AK, Stockley PG, Twarock R and Harris M. Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging. Scientific Reports, 6 22952 2016 doi:10.1038/srep22952

  3. Ross-Thriepland D, Mankouri J, Harris M. Serine phosphorylation of the hepatitis C virus NS5A protein controls the establishment of replication complexes. J Virol. 89 3123-3135 2015 doi: 10.1128/JVI.02995-14

  4. Ross-Thriepland D, Harris M  Insights into the complexity and functionality of hepatitis C virus NS5A phosphorylation.  J Virol 88 1421-1432 2014 DOI: 10.1128/JVI.03017-13