Virology

Virology research within our Institute is carried out in the MRC-University of Glasgow Centre for Virus Research (CVR). The expertise of the principal investigators of the CVR covers various aspects of virus research, ranging from molecular virology to in vivo pathogenesis, virus–cell interaction, viral immunology, viral ecology, clinical virology, virus epidemiology, mathematical modelling and bioinformatics.

PhD Research Projects

Project Title: Intrinsic immunity to HIV-1 and related retroviruses

Supervisor: Dr Sam J Wilson

  • Project outline:The ‘antiviral state’ induced by interferons attenuates the replication of most, if not all, mammalian viruses. Upon sensing of pathogens, interferon signalling results in the upregulation of hundreds of different genes. These interferon stimulated genes (ISGs) are able to mediate further signalling, modulate the cellular environment, or interfere with viruses directly, in order to impede viral replication. Despite intensive investigation, the exact contribution of individual ISGs to the antiviral state is often unknown. However, in some remarkable cases individual ISGs have been described that effectively render cells resistant to certain viruses. The extraordinary ability of these factors to restrict virus replication can protect individuals, populations and entire species from specific pathogens. This project involves searching for new antiviral factors in addition to the further characterization of antiviral molecules currently under investigation in the lab. Through expressing species variants and targeted mutants of these molecules we hope to better understand the determinants of antiviral specificity/sensitivity. Cell lines expressing putative antiviral factors will be generated and their permissivity to infection and ability to support viral replication will be investigated. Our long-term goal is to harness the information gleaned from characterising host-viral interactions to identify novel therapeutic targets and develop biotechnologies, based upon intrinsic immune factors, that could reduce the disease burden in human or livestock populations.
  • Summary Aim:This project will characterise the antiviral activity of known factors and use ISG expression screening (2) to identify novel antiviral effectors.
  • Techniques to be used:Tissue culture, virus propagation, infection and replication assays. Molecular biology, flow cytometry, confocal microscopy and biochemistry
  • References:1. Wilson SJ, Schoggins JW, Zang T, Kutluay SB, Jouvenet N, Alim MA, Bitzegeio J, Rice CM, Bieniasz PD: Inhibition of HIV-1 particle assembly by 2',3'-cyclic-ucleotide 3'-phosphodiesterase. Cell host & microbe 2012, 12(4):585-597.
    2. Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM: A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 2011, 472(7344):481-485.
    3. Wilson SJ, Webb BL, Ylinen LM, Verschoor E, Heeney JL, Towers GJ: Independent evolution of an antiviral TRIMCyp in rhesus macaques. PNAS 2008, 105(9):3557-3562.
  • Contact:Sam Wilson (sam.wilson@glasgow.ac.uk), Research Fellow, MRC - University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow

Project Title: Viral involvement in Hodgkin lymphoma

Supervisor: Professor Ruth Jarrett & Dr Alice Gallagher

  • Project outline:Hodgkin lymphoma is one of the frequently occurring lymphomas in humans and is most common in the young adult age group. A proportion of cases of Hodgkin lymphoma are associated with the Epstein-Barr virus (EBV) and we believe this association is causal. EBV-associated cases are relatively more common in childhood and older adult age groups and most young adult cases are not associated with EBV; however, epidemiological evidence suggests that infectious agents are involved in the pathogenesis of young adult Hodgkin lymphoma. A longstanding interest of our group has been to look for novel viruses in non-EBV-associated Hodgkin lymphoma in young adults. We are currently exploring the use of next generation sequencing coupled with digital transcriptome subtraction to look for novel viruses and also genetic aberrations in these cases. A challenging feature of Hodgkin lymphoma is that the tumour cells make up only ~1% of the total tumour mass; therefore these cells have to be enriched by laser microdissection or cell sorting prior to sequence analysis.
  • Summary Aim:The project will investigate viral involvement in Hodgkin lymphoma using next generation sequencing to look for viral genomes and transcripts in tumour biopsies.
  • Techniques to be used:sample processing, laser microdissection and/or cell sorting, nucleic acid extraction, next generation sequencing, bioinformatic analysis.
  • Contact:Ruth Jarrett (ruth.jarrett@glasgow.ac.uk), Professor of Molecular Pathology, Ian Botham Building, Garscube Estate, University of Glasgow, Glasgow G61 1QH

Project Title: Modelling transmission dynamics in a Drosophila model system

Supervisor: Dr Pablo Murcia

  • Project outline:Viruses cause outbreaks and epidemics that regularly pose a serious burden to both veterinary and public health, requiring effective and prompt intervention measures. A key aspect to apply proper responses to control the spread of infectious diseases is to know the transmission pathways of the viruses involved, in other words “who infected whom”. Developing tools to answer this question is a formidable task as it requires quantitative and qualitative information that is generally unavailable in the field. Our laboratory has an extensive track record on phylodynamics of influenza viruses using natural hosts at different levels (1-3). However, performing animal experiments at the population level raises ethical issues and is also logistically very difficult. We have developed a Drosophila system that allows the natural infection and transmission of viruses in flies. During this project, you will perform transmission experiments in fruit flies and recreate outbreaks in fly populations within a laboratory setting. To this end, flies will be infected with Drosophila C virus (DCV) and the presence of DCV in the flies will be determined by RT-PCR and sequencing. Transmission will also be assessed by co-housing infected and naïve flies. Parameters such as incubation period, serial interval and R0 will be determined. You will develop tools to track the spread of DCV among infected flies. This is a collaborative project between the Centre for Virus Research and the Beatson Institute for Cancer Research.
  • Summary Aim:This project will provide insight on virus transmission dynamics and develop tools to track the natural spread of viruses within a population.
  • Techniques to be used:Experimental infections- RNA extractions- RT PCR- Sequencing Sequence analysis-Modelling
  • References:1- Murcia PR, Baillie GJ, Stack JC, Jervis C, Elton D, Mumford JA, Daly J, Kellam P, Grenfell BT, Holmes EC, Wood JL (2013) Evolution of equine influenza virus in vaccinated horses. Journal of Virology. 87(8):4768-71.
    2- Hughes, J., Allen, R. C., Baguelin, M., Hampson, K., Baillie, G.J., Elton, D., Newton, J.R., Kellam, P., Wood, J.L.N, Holmes, E.C. and Murcia PR (2012) Transmission of equine influenza virus during an outbreak is characterized by frequent mixed infections and loose transmission bottlenecks. PLoS Pathogens, e1003081.
    3- Murcia, P.R., Hughes, J., Battista, P., Lloyd, L., Baillie, G.J., Ramirez-Gonzalez, R., Elton, D., Caccamo, M.J., Kellam, P., Grenfell, B.T., Holmes, E.C. and Wood, J.L.N. (2012) Evolution of an Eurasian avian-like influenza virus in naïve and vaccinated pigs. PLoS Pathogens, e1002730.
  • Contact:Pablo Murcia (Pablo.Murcia@glasgow.ac.uk, MRC - University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow. Garscube Estate, Bearsden Road, Glasgow G61 1QH, UK

Project Title: Characterization of novel antivirus compounds that inhibit hepatitis C virus infection and replication.

Supervisor: Dr Arvind H. Patel

  • Project outline:Hepatitis C virus (HCV) is a human blood-borne pathogen that causes both acute and chronic hepatitis. Over 170 million people worldwide are infected with the virus. The majority of infections progress to chronicity ultimately leading to liver cirrhosis and hepatocellular carcinoma, both necessitating liver transplantation. The efficacy of current treatment regimens has improved with the addition of new directly acting antivirals. However, there are a number of drawbacks including limitation of the therapy to patients with genotype 1 HCV infection, increased rate of adverse effects, low tolerance and high cost. Moreover, there is currently no vaccine available. A major hurdle for the design of effective treatments and vaccines is the significant genetic variation of the virus worldwide. This is a result of the inherent high mutation rate of the virus enabling it to rapidly evolve and evade the host immune responses. In order to develop new targets for effective therapy and preventative vaccines it is necessary to gain greater understanding of the processes involved in virus infection and the effect on cellular metabolism [1]. Our laboratory has developed an assay for Hepatitis C virus (HCV) infection that is suitable for high-throughput screening [2]. We have screened a large number of novel potentially anti-viral compounds against the complete virus life-cycle and also for virus entry. A cell toxicity assay was performed in parallel to rule out any false positives. This initial screen has identified several compounds of interest that target HCV infection. To date these have been further characterised into compounds that specifically inhibit virus entry and those that target a later stage of the life-cycle i.e. virus replication or assembly.
  • Summary Aim:
  • Techniques to be used:Reverse-transcription-PCR, cloning, cell culture, protein expression, ELISA, SDS-PAGE, Western immunoblotting, indirect immunofluorescence, microarrays/transcriptomics/proteomics
  • References:1. Ploss, A. & Dubuisson, J. (2012). New advances in the molecular biology of hepatitis C virus infection: towards the identification of new treatment targets. Gut 61 (Suppl 1):i25-i35. doi:10.1136/gutjnl-2012-302048.
    2. Iro, M., Witteveldt, J., Angus, A. G. N., Woerz, I., Kaul, A., Bartenschlager, R. & Patel, A. H. (2009). A reporter cell line for rapid and sensitive evaluation of hepatitis C virus infectivity and replication. Antiviral Research 83, 148-155.
  • Contact:Arvind H. Patel (Arvind.patel@glasgow.ac.uk), Programme Leader, MRC - University of Glasgow Centre for Virus Research, 8 Church Street, GLASGOW, G11 5JR,UK.

Project Title: Small molecular inhibitors of human papillomavirus replication

Supervisor: Professor Sheila V Graham

  • Project outline:Persistent infection of the epithelium with human papillomavirus type 16 (HPV16) causes ~55% of cervical cancers, other anogenital cancers and a subset of head and neck cancers [1]. Previously we demonstrated control of viral replication by serine-arginine-rich splicing factors (SRSFs) [2,3]. Moreover, recently we have also shown that expression of the viral transcription/replication factor E2 can be inhibited by small molecules that block the activity of kinases that control the functions of SRSFs. This project will assess the effect in three dimensional epithelial cell culture on HPV16 replication of a panel of five of these small molecule inhibitors. Replication will be examined using PCR to detect viral DNA, RT-PCR to quantify viral gene expression and western blotting to detect viral antigens.
  • Summary Aim:This project aims to assess the usefulness of inhibitors of cellular SRSF protein functions in controlling HPV16 replication. The outcome could be development of novel, affordable treatment for HPV-associated disease
  • Techniques to be used:Cell culture, tissue culture, viral replication assays, RT-PCR, western blotting
  • References:[1]. Bodily J, Laimins LA. Persistence of human papillomavirus infection: keys to malignant progression. Trends Microbiol. 2011 Jan;19(1):33-9.
    [2]. Mole S, Veerapraditsin T, McPhillips MG, Graham SV. Regulation of splicing-associated SR proteins by HPV-16. Biochem Soc Trans. 2006 Dec;34(Pt 6):1145-7.
    [3]. Klymenko T et al. Human papillomavirus capsid protein expression is controlled by SRSF3 in response to epithelial differentiation. Manuscript in preparation (summary available on request)
  • Contact:Shelia.graham@glasgow.ac.uk

Project Title: Innate immune responses against arboviruses

Supervisor: Dr Alain Kohl

  • Project outline:Arbovirus interactions with vectors such as mosquitoes are still poorly understood. We analyse host responses against arboviruses in vectors with an emphasis on RNA interference (RNAi) pathways. These pathways are known to have a major role in controlling arboviruses (and may influence the ability of a vector to transmit virus) yet many questions remain unanswered, in particular regarding the induction and regulation of RNAi. This project will analyse those problems by combining molecular virology and cell biology techniques.
  • Summary Aim:We aim to understand the host response in arthropod vectors of arboviruses in order to better understand the virus-host interplay and how this relates to infection efficiency. Give that vector control is key to controlling arbovirus transmission it is imperative that we understand this aspect of vector biology better.
  • Techniques to be used:Molecular virology techniques (reverse genetics etc.), cell culture techniques (including transfection), immunofluorescence, protein expression, Western and Northern blotting, deep sequencing, manipulation of mosquitoes.
  • References:Links to recent publications in Journal of Virology and PLoS Pathogens:
    http://www.ncbi.nlm.nih.gov/pubmed/23269795
    http://www.ncbi.nlm.nih.gov/pubmed/23144608
  • Contact:Centre for Virus Research, 8 Church Street, Glasgow G11 5 JR
    alain.kohl@glasgow.ac.uk

Project Title: Exploring host SUMOylation events during influenza virus infection

Supervisor: Dr Ben Hale

  • Project outline:During infection there is a struggle between virus and host as both try to create an optimal cellular environment: the host must activate self-defence mechanisms to stop virus replication, and the virus must attempt to counteract these responses whilst re-programming the cell to become a 'virus factory'. How viruses interact with the host small ubiquitin-like modifier (SUMO) proteins is currently an important area of infection biology research. SUMO acts as an important regulator of cell signalling by covalently linking to proteins and altering their structure, localization or function. As such, SUMO conjugation contributes to nearly all aspects of cell biology and can have both pro- and anti- viral functions. We are interested in trying to understand the role of SUMO modification events during influenza virus infection. We have previously shown that global cellular SUMOylation increases during influenza A virus infection of human lung epithelial cells, and have used quantitative proteomics to identify the proteins that change in SUMOylation status. We are now using influenza virus reverse genetics technologies and siRNA methods to characterise which viral and cellular factors are necessary to stimulate this response, where in the cell the response occurs, and what roles specific SUMO-modified proteins play during the virus life cycle.
  • Techniques to be used:Techniques routinely used include genetic manipulation and handling of influenza viruses, cloning and PCR mutagenesis, siRNA-mediated depletion, western blot, affinity proteomics, and immunofluorescence.
  • References:Wimmer et al., Human pathogens and the host cell SUMOylation system, J Virol, 2012, 86, 642-654.
    Everett et al., Interplay between viruses and host sumoylation pathways, Nature Reviews Microbiology, 2013, 11, 400-411.
  • Contact:Benjamin G. Hale (ben.hale@glasgow.ac.uk), Ph.D. Sir Henry Dale Fellow & Lecturer, MRC - University of Glasgow Centre for Virus Research, Scotland, UK

Project Title: Macroevolution of Gammaretroviruses

Supervisor: Dr Robert J. Gifford

  • Project outline:Vertebrate genomes typically contain thousands of DNA sequences derived from retroviruses, called ‘endogenous retroviruses’ (ERVs). These retroviral ‘fossils’ arise when retroviral infection of germ line cells leads to retroviral sequences becoming integrated into the host animal genome, so that they are vertically inherited as host alleles. ERVs range in age from hundreds to millions of years, and thus provide a unique and powerful means to investigate host-virus coevolution across long-term, macroevolutionary timescales [1, 2]. One well-studied group of infectious retroviruses are the gammaretroviruses, which cause disease in animals, and also occur in abundance as endogenous sequences in the genomes of diverse vertebrate species. I have created a database and genome mining platform for retrieving and characterizing ERVs in genome sequence databanks. This platform will be used in conjunction with phylogenetic and statistical methods to investigate the macroevolutionary history of the Gammaretrovirus genus. In particular, these approaches will be applied to describe the diversity of endogenous gammaretroviruses in distinct vertebrate lineages, to calibrate the timescale of gammaretrovirus evolution, and to reveal historical patterns of gammaretrovirus spread between species and geographic regions. This information will in turn be linked to an analysis of selection in vertebrate host genes known to restrict retroviral infection to reconstruct the history of genetic conflict between gammaretroviruses and their vertebrate hosts [3].
  • Summary Aim:Bioinformatic analysis of published genome sequence data will be used to investigate the co-evolutionary relationships of vertebrates and gammaretroviruses, and to derive general ecological and macroevolutionary principles governing the emergence and spread of blood-borne viral pathogens.
  • Techniques to be used:: bioinformatic sequence analysis, phylogenetic reconstruction, genome mining tools, statistical analysis, and optionally, PERL & PYTHON programming.
  • References:1. Katzourakis, A., et al., Macroevolution of complex retroviruses. Science, 2009. 325(5947): p. 1512.
    2. Gifford, R.J., Viral evolution in deep time: lentiviruses and mammals. Trends Genet, 2012. 28(2): p. 89-100.
    3. Compton, A.A., H.S. Malik, and M. Emerman, Host gene evolution traces the evolutionary history of ancient primate lentiviruses. Philos Trans R Soc Lond B Biol Sci, 2013. 368(1626): p. 20120496.
  • Contact:Robert Gifford (robert.gifford@glasgow.ac.uk), Senior Research Fellow, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow

Overview

The MRC – University of Glasgow Centre for Virus Research (CVR) sits within the Institute of Infection, Immunology and Inflammation. The CVR is the largest virology-focussed research centre in the UK and brings together a critical mass of researchers studying human and animal viruses and viral diseases.

The CVR provides excellent facilities and opportunities for cross-disciplinary projects and the delivery of a comprehensive programme of training in contemporary, multi-disciplinary, virology research. The Centre includes research programmes in arboviruses, Epstein Barr virus, feline calicivirus, herpes viruses, hepatitis C virus, influenza, retroviruses and papillomaviruses. Further details of our CVR research programmes.

 Cross cutting research themes and expertise include:

  • antiviral immunity, 
  • virus discovery, 
  • viral bioinformatics, mathematical modelling and genomics to guide new approaches to the understanding and management of viral infections, 
  • structural biology/cryo-electron microscopy and viral evolutionary dynamics. 
  • molecular virology to in vivo pathogenesis, 
  • virus-cell interactions, 
  • viral immunology,
  • viral ecology, 
  • viral oncology, 
  • clinical and veterinary virology, 
  • viral diagnostics, 
  • virus epidemiology

Our excellent facilities underpin a bench to bedside approach that will equip you with training complementary to a range of career options, and you can tailor your study pathway to the precise aspects of infection and immunology that suit your objectives. Through their research interests in drug development, vaccines and diagnostics, many of our project supervisors have strong links with industry.

Study options

PhD programmes in virology last 3-4 years and are based on individual research projects covering the interest of the supervisor.

 

 

Supervisors

All our postgraduate research students are allocated a supervisor who acts as the main source of academic support and research mentoring.

You may want to identify a potential supervisor and contact them to discuss your research proposal before you apply.

Entry requirements

Awarded or expected 1st class or high upper 2nd class BSc degree.

English Language requirements for applicants whose first language is not English.

Fees and funding

Fees

2016/17

  • £4,121 UK/EU
  • £18,900 outside EU

Prices are based on the annual fee for full-time study. Fees for part-time study are half the full-time fee.

Additional fees for all students:

  • Submission by a research student £440
  • Submission for a higher degree by published work £890
  • Submission of thesis after deadline lapsed £140
  • Submission by staff in receipt of staff scholarship £680
  • Research students registered as non-supervised Thesis Pending students (50% refund will be granted if the student completes thesis within the first six months of the period) £250
  • General Council fee £50
  • Depending on the nature of the research project, some students will be expected to pay a bench fee to cover additional costs. The exact amount will be provided in the offer letter.

2017/18

  • £4,195 UK/EU*
  • £19,500 outside EU

Prices are based on the annual fee for full-time study. Fees for part-time study are half the full-time fee.

* We expect that tuition fees for EU students entering in 2017 will continue to be set at the same level as that for UK students.  However, future funding arrangements for EU students will be determined as part of the UK’s discussions on its future relationship.  If you are thinking of applying for 2017 entry, we would encourage you to do so in the usual way. For further information, please see the Research Councils UK statement on international collaboration and Universities UK Brexit FAQs for universities and students.

Additional fees for all students:

  • Fee for re-submission by a research student: £460
  • Submission for a higher degree by published work: £1,050
  • Submission of thesis after deadline lapsed: £250
  • Submission by staff in receipt of staff scholarship: £730
  • Research students registered as non-supervised Thesis Pending students (50% refund will be granted if the student completes thesis within the first six months of the period): £300
  • Registration/exam only fee: £150
  • General Council fee: £50

Alumni discount

A 10% discount is available to University of Glasgow alumni. This includes graduates and those who have completed a Junior Year Abroad, Exchange programme or International Summer School at the University of Glasgow. The discount is applied at registration for students who are not in receipt of another discount or scholarship funded by the University. No additional application is required.

 

Funding

Support

The College of Medical, Veterinary and Life Sciences Graduate School provides a vibrant, supportive and stimulating environment for all our postgraduate students. We aim to provide excellent support for our postgraduates through dedicated postgraduate convenors, highly trained supervisors and pastoral support for each student.
 
Our over-arching aim is to provide a research training environment that includes:

  • provision of excellent facilities and cutting edge techniques
  • training in essential research and generic skills
  • excellence in supervision and mentoring
  • interactive discussion groups and seminars
  • an atmosphere that fosters critical cultural policy and research analysis
  • synergy between research groups and areas
  • extensive multidisciplinary and collaborative research
  • extensive external collaborations both within and beyond the UK 
  • a robust generic skills programme including opportunities in social and commercial training

Research environment

If you study with us, you will join a large community of  postgraduate taught and research students. Our institute brings together world-leading basic, applied, clinical and translational researchers to study infection with a focus on the viral, parasitic and bacterial pathogens of both humans and animals, and immunology and inflammation with a focus on chronic inflammatory diseases.

Despite the continual development of new therapies, antibiotics and vaccines, chronic inflammatory and infectious diseases still pose persistent health threats. We aim to:

  • understand the basic science of the immune systems and how the immune system can inturn affect disease outcome understand the biology of parasites, viruse and bacteria and the interactions with their hosts, that in turn leads to high levels of infectious diseases worldwide
  • develop therapies (drugs and vaccines) targeted on these processes
  • explore new treatments and strategies in clinical and translational medicine.

Research centres

We offer a wide range of cutting-edge research facilities, including core facilities in fluorescence activated cell sorting analysis, histology and state-of-the-art imaging. In addition, we offer the IVIS imaging system, high content screening microscopy, mass spectrometry, an X-ray capable FX Pro bioluminescence imaging system and a protein purification service. Also available are a wide range of molecular, immunological and biochemical analysis tools.