Faculty of Biological Sciences

Prof Mark Harris

BSc, Plymouth, PhD 1987, Glasgow
Professor of Virology
School of Molecular and Cellular Biology

Background: 1987-1988, Post-doctoral position with Dr Possee, NERC Institute of Virology, Oxford; 1988-1993 PostDoctoral Research Fellow, MRC Retrovirus Research Laboratory, Department of Veterinary Pathology, Glasgow; 1993-1998 MRC Senior Research Fellowship, MRC Retrovirus Laboratory, Glasgow, Department of Microbiology, University of Leeds.

Contact:  Garstang 8.59, +44(0) 113 34 35632, email address for  

You can read more about Prof Harris's interests here:
www.astbury.leeds.ac.uk/People/staffpage.php?StaffID=MH


Research Interests

Virus-host interactions in hepatitis C virus and HIV-1

Studies on the replication and assembly of hepatitis C virus

Hepatitis C virus is an important human pathogen that infects an estimated 170 million people worldwide. My laboratory is interested in understanding the molecular mechanisms by which this virus replicates its genome and assembles into new virus particles, with a particular focus on the virus-host interactions that underpin these processes. The ultimate goal of this research is to identify new targets for the development of novel antivirals. Work in my laboratory is funded mainly by the Wellcome Trust, principally via a recent Senior Investigator Award.

Specific projects include:

1) Functional studies on the non-structural NS5A protein. 

NS5A is a phosphoprotein that plays as yet undefined but essential roles in both genome replication and virus assembly. We are using a combination of techniques to investigate these roles, for example mutagenesis to define key residues, protein-protein interaction analysis to identify cellular (and viral) partners and mass spectrometry to identify phosphorylation sites. We are also investigating the interaction of NS5A with viral RNA, with the aim of identifying RNA–binding motifs within NS5A and defining the RNA sequences that are bound by the protein. 

NS5A also perturbs cellular physiology by modulating a number of signalling pathways, eg MAP kinases, PI3K. In this regard we have a particular interest in the interactions of NS5A with cellular SH3 domain containing proteins such as Src-family kinases. These interactions mediate (amongst others) inhibition of a pro-apoptotic potassium channel (Kv2.1), rendering infected cells resistant to oxidative stress induced apoptosis.

2) Understanding the structure and composition of the RNA replication complex. 

We are using both proteomic and imaging techniques to probe the multiprotein complex that replicates the viral genome. For example – purifying the nascent RNA from infected cells and identifying the associated proteins by mass spectrometry and genetically tagging the virus to enable either high resolution EM or fluorescent imaging.

3) Application of structure-based drug design to develop new HCV therapeutics.

In collaboration with Prof Colin Fishwick (Chemistry) we are exploiting the existing structural information about HCV non-structural proteins (in particular NS2 and NS5A) to identify candidate antivirals. These will be tested using established methodologies (sub-genomic replicons, infectious virus assays) and then subject to iterative SAR to optimise their potential to inhibit virus replication.

HIV Nef studies

In addition to studies on HCV, we are using structure-based drug design to design inhibitors of the HIV-1 Nef protein. Nef is a key protein in HIV pathogenesis and we have determined the crystal structure of the full-length myristoylated HIV-1 Nef (in collaboration with Dr Jo Jaeger – currently in Albany, NY).  These studies have identified compounds that have been assayed using FACS to demonstrate inhibition of Nef induced CD4 and MHC-I down-modulation, and shown by ITC to bind to Nef.

We are part of the Virology and Structural Molecular Biology groups
Research in my laboratory is funded by the Wellcome Trust, studentships are funded by the Wellcome Trust and  BBSRC.
 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Virus-host interactions in hepatitis C virus and HIV-1.
  • Replication of hepatitis C virus.

See also:

Modules managed

MICR2121 - Molecular Virology
MICR2222 - Medical Virology

Modules taught

BIOC3221/22/BIOL3210/MICR3211 a - ATU - World of Viruses
BIOL2301 - Intermediate Skills for Biological Sciences
BIOL2301/03/05/MICR2320 - Skills for Biol Sci, Biosciences and Microbiology
BIOL3305/3400/BIOC3303/MICR3325 - BIOL/BIOC/MICR advanced skills
BIOL5171M - Infectious & Non-infectious Diseases
BIOL5312M - Bioimaging
BIOL5371M - Research Planning and Scientific Communication
BIOL5373M - Protein Engineering Laboratory Project
BMSC2210 - Chemotherapy
MICR2121 - Molecular Virology
MICR2222 - Medical Virology
MICR3211 - Advanced Topics in Microbiology 2
MICR3325 - Skills for Microbiologists 3

Committees

Member of Masters Taught Student Education Committee (Co-opted member)

Centre membership: The Astbury Centre for Structural Molecular Biology

Group Leader Prof Mark Harris  (Professor of Virology)

Virus-host interactions in hepatitis C virus and HIV-1 

Dr Niluka Goonawardane  (Research Fellow)

Dr Roland Remenyi  (Research Fellow)

Developing research tools to visualise viral infection by advanced microscopy 

Mr Carsten Zothner  (Technician)


Postgraduates

Christopher Bartlett (Primary supervisor) 50% FTE
Michalis Christoforou (Primary supervisor) 50% FTE
Yanni Gao (Primary supervisor) 50% FTE
Lorna Kelly (Primary supervisor) 100% FTE
Joseph Lattimer (Primary supervisor) 50% FTE
Raymond Li (Primary supervisor) 50% FTE
Grace Roberts (Primary supervisor) 50% FTE
Chunhong Yin (Primary supervisor) 50% FTE
Lauren Branfield (Co-supervisor) 33% FTE
Eleni-Anna Loundras (Co-supervisor) 50% FTE