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Andrew Woodman


Hello, and welcome to my ePortfolio!


About me

I have recently completed my Ph.D in the Lab of Professor David Evans (www.evanslab.org.uk). I chose to continue my studies at Warwick after graduating with a first class degree in Microbiology and Virology (2011). During my undergraduate degree, I was fortunate to have completed a BBSRC funded summer placement in the Lab of Dr. Keith Leppard (2010). This gave me a great insight for the Ph.D that I have just completed. I will be taking up my first Post-doctoral position in the lab of Professor Craig Cameron at Penn State University in August 2015, continuing my research on recombination.


My Research

The Evans Lab bases its research on positive sense RNA viruses. I am currently investigating the viral and host factors that influence genetic recombination in enteroviruses, with poliovirus being the type species.

Briefly, genetic recombination involves the exchange of sequences between segmented and non-segmented genomes. Single stranded RNA viruses, like poliovirus, are believed to exchange sequences via a ‘copy-choice’ mechanism (Kirkegaard & Baltimore, 1986). In its simplest form the model requires two RNA templates and the viral replication machinery for successful template switching to occur. The ‘donor’ template recruits the replicase leading to replication initiation. At a point during mid-elongation the replicase leaves the ‘donor’ strand and associates with an ‘acceptor’ template, where replication of the nascent RNA continues (figure 1). Indeed, experimental evidence has suggested that template switching occurs during negative strand synthesis (Kirkegaard & Baltimore, 1986).


Copy choice mechanism

Figure 1: Copy-choice mechanism
The replication machinery is shown in purple. During anti-sense strand synthesis the viral RNA dependent RNA polymerase (replicase) along with the nascent RNA switches template strands from donor to acceptor. The replication machinery continues along the acceptor template. The final anti-sense strand produced contains sequences from both donor and acceptor strands. Image adapted from Flint, S. J., Enquist, L. W., Racaniello, V. R. & Skalka, A. M. (2004). Principles of Virology, 2 edn, pp. 918. Washington: ASM Press.

Enteroviruses have evolved an error-prone RNA dependent RNA polymerase (3Dpol). Some mutations within a population may provide a selective advantage and therefore predominate in the population at any one time. However, far greater genetic diversity occurs by recombination events, where vast areas of the non-structural coding region of the virus genome change in one step. Interestingly, many of the current circulating enteroviruses have arisen from recombination events, emphasising the importance of this evolutionary mechanism. Additionally, vaccine derived outbreaks of Poliomyelitis have been directly linked to recombination (Kew et al 2000).

We have developed a system that utilises two replication deficient viral genomes that alone cannot produce virus (figure 2). However, when co-transfected into permissive cells, a recombination event can occur that produces viable infectious virus. Our system will allow us to manipulate host and viral factors, which will enable us to elucidate their contribution to the recombination event.


 Recombination assay

Figure 2: Recombination Assay
Genome A has a mutated CRE, depicted by the red cross. Briefly, this alteration to the RNA sequence ensures viral RNA replication is limited to anti-sense RNA only. Genome B is known as a Sub-genomic replicon, this RNA species can complete a full replication cycle, but lacks the key structural genes which have been replaced by a firefly luciferase gene. Only a recombination event, shown by recombinant genome 2, can produce a fully functional viral RNA strand.


Other interests

I have a keen interest in many sports and play for a local football team in Evesham, contributing to the group via various roles from team captain to player-manager. Travel and food are also passions of mine, and I have been very fortunate to have visited many areas, experiencing their culture and cuisine.

Andrew Woodman

Andrew Woodman

A dot Woodman at warwick dot ac dot uk




David Evans 

Supervisor

Prof. David Evans







Polio type 1

Poliovirus type 1 particle

 (Hogle, Chow & Filman, 1985)