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Laurence Tiley

Control of influenza virus replication

My research focuses on three areas of virology:

Superchicken
Is it a bird… is it a plane… or a flu-resistant super-chicken?
1. Transgenic strategies for controlling influenza virus replication in livestock hosts. We are exploring molecular approaches to interfere with influenza virus replication in vivo and testing these using transgenic livestock (chickens and pigs). 

 

2. Enhancing vaccine production in eggs: By altering the expression pattern of viral receptors and disrupting antiviral pathways of host cells (specifically chick embryos in fertilised eggs) we are generating eggs that can propagate a wider range of viruses and produce higher yields for vaccine production.

 

3. Investigating the dynamics of influenza virus mixed infections in cell culture and in vivo. Using "barcoded" viruses we are investigating the frequency and consequences of mixed infections by influenza virus. We are particularly interested in how viral quasispecies can support the persistence of lower-fitness but evolutionarily significant variants within the population.


 

Key Publications

Asparagine 631 variants of the Chicken Mx protein do not inhibit influenza replication in primary chicken embryo fibroblast cells or in vitro surrogate assays. Benfield C., Lyall, J., Kochs, G. and Tiley, L.S. 2008. J. Virol 82:7533-7539

Suppression of avian influenza transmission in genetically modified chickens. Lyall. J.E., Irvine R.M., Sherman A., McKinley T.J., Núñez A., Purdie A., Outtrim L., Brown I., Rolleston-Smith G., Sang H. and Tiley L.S. 2011 Science. 331:223-226

Bourret, V., Lyall, J., Ducatez, M.F., Guérin, J.L. and  Tiley, L. 2012. Development of an improved polykaryon-based influenza virus rescue system. BMC Biotechnol. 12:69. 

The role and assembly mechanism of nucleoprotein in influenza A virus ribonucleoprotein complexes Turrell, L., Lyall, J.E., Tiley, L.S., Fodor, E. and Vreede, F.T. 2013. Nature Comms. 4:1591. 

Whole-genome, deep pyrosequencing analysis of a duck influenza A virus evolution in swine cells. Bourret V, Croville G, Mariette J, Klopp C, Bouchez O, Tiley L, Guérin JL. 2013. Infect Genet Evol. 18:31-41. doi: 10.1016/j.meegid.2013.04.034. Epub 2013

 

Dr Laurence Tiley

Senior Lecturer in Molecular Virology

Lst21@cam.ac.uk

Contact details: 

Group members:  Ian Mickleburgh (Post-doc), JinQi Fu (Ph.D student)

Plain English

Introducing new genes into chickens and pigs to make them resistant to virus infection. The goal is to reduce the economic and welfare impact of influenza virus in livestock and also to reduce the possibility of the virus using these species as "bridges" to cross over from the natural reservoir of flu (the wild aquatic bird population) into humans (that could potentially lead to a new pandemic).

Many vaccines are produced in eggs. We are genetically modifying chickens to produce eggs that grow a wider range of viruses  and  produce greater yields.

Under normal infection conditions, host cells are rarely infected by a single virus particle. Usually they will be infected by many particles and this has consequences for how the virus is able to overcome host defences and how it evolves. We are using viruses with unique molecular "fingerprints" or "barcodes" that enable mixed infections to be identified and studied in the laboratory and in infected animals.

Funding

BBSRC
Industrial partnership funding

Laurence is accepting PhD Student applications

Laurence is also available for consultancy