Faculty of Biological Sciences

Dr Andrew Macdonald

BSc, Leeds; PhD 2001, Leeds
Associate Professor in Virology
School of Molecular and Cellular Biology

Background: Post-doctoral work in the Division of Microbiology, University of Leeds with Professor Mark Harris (2001 - 2004); MRC funded Career Development Fellow, MRC Protein Phosphorylation Unit, University of Dundee with Dr Simon Arthur (2004 - 2006). RCUK funded Independent investigator (2006 - present).

Contact:  Garstang 8.54 (lab) 8.53e (Office) | +44(0) 113 34 33053 | email address for  

You can read more about Dr Macdonald's interests here:
www.fbs.leeds.ac.uk/staff/Macdonald_A/

Research Interests

Studies of small DNA tumour viruses that cause disease in humans

Members of the Papovaviridae, which includes the Papillomaviruses and Polyomaviruses, are the causative agents of a number of severe diseases in humans. Notable examples include oral and anogenital cancers caused by human papillomavirus (HPV), kidney transplant rejection caused by BK polyomavirus (BK PyV) and brain disease caused by JC polyomavirus (JC PyV). Current therapeutic strategies to treat these viruses are lacking. 

We have established a multi-disciplinary research group to undertake a broad ranging analysis of these viruses in an effort to identify new targets for therapeutic intervention.  These studies continue to reveal novel information about this family of viruses.

Human papillomaviruses

We are focussing on the role of virus proteins both in transformation and their requirement during the virus lifecycle.  We are particularly interested in a virus oncoprotein called E5, which is poorly understood. Our research provided the first evidence that the E5 protein is a virus-encoded ion channel or viroporin (Wetherill et al., 2012).  Importantly, small molecule inhibitors against this channel prevented the transforming phenotype of this protein. E5 is the first known oncogenic virus ion channel.  We are further characterising the role of the E5 protein in the virus life cycle using three dimensional organotypic raft culture models.  These cultures recapitulate the development of the skin in culture and are the only method to study the entire HPV lifecycle in the laboratory.  We have shown that E5 is necessary for the later stages of the virus lifecycle using these  methods.  We are also mapping the E5 interactome using proteomic approaches in an effort to better understand the mechanisms of E5 pathogenesis.

In additional studies using a small molecule inhibitor screen, we have identified novel host determinants of HPV infection.  We are currently using a combination of cellular and virological techniques to understand the molecular basis for the role of these host proteins in the HPV lifecycle.  Excitingly, these host proteins may be a novel target for therapeutic intervention to treat HPV-associated disease.

 

Human polyomaviruses

We have recently started working on these disease-causing viruses and have already made great progress in our understanding of their lifecycles.  Our research again focusses both on virus and host factors that are needed for an effective infection.  We are mapping new virus targets for therapeutics and have already identified novel host proteins that are needed by BK virus to complete an infection. 

 

For more information about the research and our group at Leeds, please see the Macdonald group web page.



Potential undergraduate and post-graduate projects.
We are keen to recruit exceptional individuals and undergraduate and post-graduate level to join our multi-disciplinary team of researchers. We are a well-funded laboratory, based in refurbished laboratory space with access to state of the art molecular and cellular facilities.  We have a thriving mix of post-doctoral and graduate scientists and we publish in high impact peer reviewed journals.

 

 

Faculty Research and Innovation


Studentship information

Undergraduate project topics:

  • Human papillomaviruses and their links to cancer
  • Studying polyomavirus lifecycle and pathogenesis
  • Host factors required for virus lifecycles
  • Immune evasion strategies of viruses

Postgraduate studentship areas:

  • Human papillomaviruses and their links to cancer
  • Studying polyomavirus lifecycle and pathogenesis
  • Host factors required for virus lifecycles
  • Immune evasion strategies of viruses

See also:

Admin roles

FBS Faculty Board
School Management Committee

Modules managed

BIOC3160 - Lab/Lit/Comp Research Project
BIOL3306 - Biol Sciences Research Project
MICR3080 - Microbiology Research Programme
MICR3110 - Microbiology Research Programme
MICR3190 - Microbiology Research Programme
MICR3370 - Microbiology Research Programme

Modules taught

BIOC2301/BIOL2210 - Integrated Biochemistry/Biological Membranes
BIOC2301/MICR2120 - Integrated Biochemistry/Medical Bacteriology
BIOC3111/12/13/BIOL3112/MICR3120/BIOL5246M - ATU 19 - Immune evasion
BIOC3111/12/13/BIOL3112/MICR3120/BMSC3143/44/45/46/BIOL5246M a - ATU 20 - Innate immunity
BIOC3111/12/13/BIOL3112/MICR3120/BMSC3143/44/45/56/BIOL5246M b - ATU 01 - Adaptive immunity
BIOC3160 - Lab/Lit/Comp Research Project
BIOC3900 - Cancer Biology
BIOL1302 - Intro Skills - Biological Sci
BIOL2301 - Intermediate Skills for BioSci
BIOL2301/05/MICR2320 - Skills for Biol Sci, Biosciences and Microbiology
BIOL3112 - Adv Topics for Biol Sciences 1
BIOL3399 - Extended Research Project Preparation
MICR1120/3342 - Introduction to Microbiology
MICR1220 - Introduction to Immunology
MICR2121 - Molecular Virology
MICR2221 - Medical Immunology
MICR2222 - Medical Virology
MICR2320 - Skills for Microbiologists 2
MICR3080 - Microbiology Research Programme
MICR3080/3110/3190/3370/BIOL3306 - MICR/BIOL projects
MICR3211/BIOL3210 a - ATU 11 - Emerging infections
MICR3325 - Skills for Microbiologists 3
MICR3370 - Microbiology Research Programme

Centre membership: The Astbury Centre for Structural Molecular Biology

Group Leader Dr Andrew Macdonald  (Associate Professor in Virology )

Studies of small DNA tumour viruses that cause disease in humans 


Ms Rajni Bhardwaj  (Research Technician)

Dr Emma Prescott  (Research Fellow)

Dr Christopher Wasson  (Research Fellow)


Postgraduates

Hussein Abdul-Sada  
Samuel Dobson  
Rebecca Holdich  
Sara Jasem  
Margarita Panou  
Daniel Williamson  

Richards KH; Doble R; Wasson CW; Haider M; Blair GE; Wittmann M; Macdonald A Human Papillomavirus E7 oncoprotein increases production of the anti-inflammatory IL-18 binding protein (IL-18BP) in keratinocytes Journal of Virology 88 4173-4179, 2014
DOI:10.1128/JVI.02546-13
View abstract

Stakaitytė G; Wood JJ; Knight LM; Abdul-Sada H; Adzahar NS; Nwogu N; Macdonald A; Whitehouse A Merkel cell polyomavirus: molecular insights into the most recently discovered human tumour virus. Cancers (Basel) 6 1267-1297, 2014
DOI:10.3390/cancers6031267
View abstract

Remenyi J; van den Bosch MW; Palygin O; Mistry RB; McKenzie C; Macdonald A; Hutvagner G; Arthur JS; Frenguelli BG; Pankratov Y miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity. PLoS One 8 e62509-, 2013
DOI:10.1371/journal.pone.0062509
View abstract

Griffiths DA; Abdul-Sada H; Knight LM; Jackson BR; Richards K; Prescott EL; Peach AHS; Blair GE; Macdonald A; Whitehouse A Merkel Cell Polyomavirus Small T Antigen Targets the NEMO Adaptor Protein To Disrupt Inflammatory Signaling JOURNAL OF VIROLOGY 87 13853-13867, 2013
DOI:10.1128/JVI.02159-13

Naqvi S; Macdonald A; McCoy CE; Darragh J; Reith AD; Arthur JS Characterization of the cellular action of the MSK inhibitor SB-747651A. Biochem J 441 347-357, 2012
DOI:10.1042/BJ20110970
View abstract

Wu W; Macdonald A; Hiscox JA; Barr JN Different NF-κB activation characteristics of human respiratory syncytial virus subgroups A and B. Microb Pathog 52 184-191, 2012
DOI:10.1016/j.micpath.2011.12.006
View abstract

Wetherill LF; Holmes KK; Verow M; Müller M; Howell G; Harris M; Fishwick C; Stonehouse N; Foster R; Blair GE; Griffin S; Macdonald A High-risk human papillomavirus E5 oncoprotein displays channel-forming activity sensitive to small-molecule inhibitors. J Virol 86 5341-5351, 2012
DOI:10.1128/JVI.06243-11
View abstract

Richards KH; Macdonald A Putting the brakes on the anti-viral response: negative regulators of type I interferon (IFN) production MICROBES INFECT 13 291-302, 2011
DOI:10.1016/j.micinf.2010.12.007

McFadden N; Bailey D; Carrara G; Benson A; Chaudhry Y; Shortland A; Heeney J; Yarovinsky F; Simmonds P; Macdonald A; Goodfellow I Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4. PLoS Pathog 7 e1002413-, 2011
DOI:10.1371/journal.ppat.1002413
View abstract

Gamlen T; Richards KH; Mankouri J; Hudson L; McCauley J; Harris M; Macdonald A Expression of the NS3 protease of cytopathogenic bovine viral diarrhea virus results in the induction of apoptosis but does not block activation of the beta interferon promoter J GEN VIROL 91 133-144, 2010
DOI:10.1099/vir.0.016170-0

Emmott E; Rodgers MA; Macdonald A; McCrory S; Ajuh P; Hiscox JA Quantitative Proteomics Using Stable Isotope Labeling with Amino Acids in Cell Culture Reveals Changes in the Cytoplasmic, Nuclear, and Nucleolar Proteomes in Vero Cells Infected with the Coronavirus Infectious Bronchitis Virus MOL CELL PROTEOMICS 9 1920-1936, 2010
DOI:10.1074/mcp.M900345-MCP200

Mankouri J; Fragkoudis R; Richards KH; Wetherill LF; Harris M; Kohl A; Elliott RM; Macdonald A Optineurin Negatively Regulates the Induction of IFN beta in Response to RNA Virus Infection PLOS PATHOG 6 -, 2010
DOI:10.1371/journal.ppat.1000778

Mankouri J; Dallas ML; Hughes ME; Griffin SDC; Macdonald A; Peers C; Harris M Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence P NATL ACAD SCI USA 106 15903-15908, 2009
DOI:10.1073/pnas.0906798106

Poole E; Groves I; Macdonald A; Pang Y; Alcami A; Sinclair J Identification of TRIM23 as a Cofactor Involved in the Regulation of NF-kappa B by Human Cytomegalovirus J VIROL 83 3581-3590, 2009
DOI:10.1128/JVI.02072-08

Wittmann M; Macdonald A; Renne J IL-18 and skin inflammation AUTOIMMUN REV 9 45-48, 2009
DOI:10.1016/j.autrev.2009.03.003

Ananieva O; Macdonald A; Wang X; Mccoy CE; McIlrath J; Tournier C; Arthur JSC ERK5 regulation in naive T-cell activation and survival EUR J IMMUNOL 38 2534-2547, 2008
DOI:10.1002/eji.200737867

Mccoy CE; MacDonald A; Morrice NA; Campbell DG; Deak M; Toth R; McIlrath J; Arthur JSC Identification of novel phosphorylation sites in MSK1 by precursor ion scanning MS BIOCHEM J 402 491-501, 2007
DOI:10.1042/BJ20061183

Kaiser M; Wiggin G; Lightfoot K; Arthur JSC; Macdonald A MSK regulate TCR-induced CREB phosphorylation but not immediate early gene transcription. European Journal of Immunology 37 2583-2595, 2007
DOI:10.1002/eji.200636606

Macdonald A; Campbell DG; Toth R; McLauchlan H; Hastie CJ; Arthur JSC Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-X-L BMC CELL BIOL 7 -, 2006
DOI:10.1186/1471-2121-7-1

Macdonald A; Mazaleyrat SL; McCormick CJ; Street AA; Burgoyne NJ; Jackson RM; Cazeaux V; Shelton HA; Saksela K; Harris MPG Further studies on hepatitis C virus NS5A–SH3 domain interactions: identification of residues critical for binding and implications for viral RNA replication and modulation of cell signalling Journal of General Virology 86 1035-1044, 2005
DOI:10.1099/vir.0.80734-0
View abstract

Street A; Macdonald A; McCormick C; Harris M Hepatitis C virus NS5A-mediated activation of phosphoinositide 3-kinase results in stabilization of cellular beta-catenin and stimulation of beta-catenin-responsive transcription. J Virol 79 5006-5016, 2005
DOI:10.1128/JVI.79.8.5006-5016.2005
View abstract

Macdonald A; Chan JKY; Harris M Perturbation of epidermal growth factor receptor complex formation and Ras signalling in cells harbouring the hepatitis C virus subgenomic replicon J GEN VIROL 86 1027-1033, 2005

McCormick CJ; Challinor L; Macdonald A; Rowlands DJ; Harris M Introduction of replication-competent hepatitis C virus transcripts using a tetracycline-regulable baculovirus delivery system. J Gen Virol 85 429-439, 2004
View abstract

Street A; Macdonald A; Crowder K; Harris M The Hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase-dependent survival signaling cascade. J Biol Chem 279 12232-12241, 2004
DOI:10.1074/jbc.M312245200
View abstract

Macdonald A; Harris M Hepatitis C virus NS5A: tales of a promiscuous protein. J Gen Virol 85 2485-2502, 2004
DOI:10.1099/vir.0.80204-0
View abstract

Macdonald A; Crowder KJ; Street AA; McCormick CJ; Harris MPG The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity Journal of General Virology 85 721-729, 2004
DOI:10.1099/vir.0.19691-0

Macdonald A; Crowder KJ; Street AA; McCormick CJ; Saksela K; Harris M The hepatitis C virus non-structural NS5A protein inhibits activating protein-1 function by perturbing Ras-ERK pathway signaling Journal of Biological Chemistry 278 17775-17784, 2003
DOI:10.1074/jbc.M210900200
View abstract