Leighton Pritchard
Current research interests
- Computational biology and bioinformatics.
- Oomycete and bacterial plant pathogens.
- Systems biology of plant-pathogen interactions.
- Comparative genomics of plant pathogens.
Research interests
My research centres around plant-pathogen interactions. Primarily, I aim to understand what it is about microbial plant pathogens that enables them to infect plants, and what it is is about plants that allows microbes to cause disease on them. As a computational biologist, most of my work involves the computational and mathematical analysis of biological data such as genome sequences, microarray gene expression profiles, and networks of metabolic and regulatory processes.
Systems biology
- Plant cells contain complex systems of signalling, regulatory and metabolic networks (Pritchard and Birch, 2011). These are perturbed by invading microbes, which introduce effector proteins and other molecular species into the plants they infect. Invaded plants detect molecular components of the invading pathogen and changes to their cellular networks, usually responding with effective resistance. I am interested in the implications of the dynamics and structure of these cellular networks, for the development of plant disease caused by microbial pathogens.
Genomics and comparative genomics of plant pathogens
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Genome sequencing has changed the face of biology, and revolutionised our understanding of the molecular biology of microbes. Sequenced genomes provide an opportunity for comparative genomics to determine which features might confer particular functions and behaviours on an organism. Sequence annotation also remains a challenge, even for well-studied organisms. I use computational and machine-learning approaches to aid classification of genome features and identify features that may be associated with the ability of a microbe to cause disease.
Phytophthora infestans (Haas et al. 2009) and Pectobacterium atrosepticum (Bell et al. 2004) genome projects. Comparative genomics of plant pathogens (Toth et al. 2006), including microarray comparative genomic hybridisation (Pritchard et al. 2009). Identification and classification of pathogen effectors (McNally et al. 2012, Whisson et al. 2007, Haas et al. 2009) and other genomic features (Jupe et al. 2012, Avrova et al. 2007, Kikuchi et al. 2007, Whisson et al. 2005, Bell et al. 2004). Diagnostic assays from rough draft genome sequences (Pritchard et al. in preparation).
Oomycete and bacterial plant pathogens
- Much of my work is directed towards providing insight into and understanding of plant-pathogen interactions. This is in support of the practical goal of reducing the impact of severe and financially significant crop diseases caused by oomycete and bacterial plant pathogens, such as Phytophthora infestans and Dickeya species. In order to understand the relationship between our models and the outcome of infection, we need to appreciate both the biological and the mathematical details of the problem. Oomycete effector proteins (Birch et al. 2009, Birch et al. 2006, Armstrong et al. 2005), and interactions with plant defences (Gilroy et al. 2007). Microarray design and analysis of gene expression profiles in bacterial plant pathogens (McNally et al. 2012, Antunez-Lamas et al. 2009, Ravirala et al. 2007). Persistence of human pathogenic bacteria on plants (Holden et al. 2008).
Computational Biology and Bioinformatics
- Bioinformatics and mathematics are the tools that I use to study and make sense of biological sequences and other data. I am interested in visualisation tools for large datasets, and a collaboration in this area with Ian Toth, Michel Perombelon, and Prof. Elaine Shemilt of the Duncan of Jordanstone College of Art and Design resulted in exhibitions in Dundee and Singapore. I have also contributed code to open source bioinformatics projects, including Biopython. Visualisation of comparative genomic data (Pritchard et al. 2006). Directed evolution and error-prone PCR (Pritchard et al. 2005). Protein sequence-structure-function analysis, including covariation analysis (Pritchard et al. 2003, Pritchard et al. 2001, Pritchard and Dufton 2000, Pritchard and Dufton, 1999)
Collaborations
- Plant pathogen research is a multidisciplinary effort, and I collaborate with a number of researchers in a range of fields, in the UK and internationally.
Bibliography
- Pritchard, L., Holden, N.J., Bielaszewska, M., Karch, H., Toth, I.K. 2012 Alignment-Free Design of Highly Discriminatory Diagnostic Primer Sets for Escherichia coli O104:H4 Outbreak Strains. PLoS ONE 7: e34498.(doi:10.1371/journal.pone.0034498.t001)
- Rio-Alvarez, I., Rodríguez-Herva, J.J., Cuartas-Lanza, R., Toth, I., Pritchard, L., et al. 2012 Genome-Wide Analysis of the Response of Dickeya dadantii 3937 to Plant Antimicrobial Peptides. Mol Plant Microbe Interact 25: 523–533. (doi:10.1094/MPMI-09-11-0247)
- Milne, I., Stephen, G., Bayer, M., Cock, P.J.A., Pritchard, L., et al. 2012 Using Tablet for visual exploration of second-generation sequencing data. Brief Bioinformatics. (doi:10.1093/bib/bbs012)
- Jupe, F., Pritchard, L., Etherington, G.J., Mackenzie, K., Cock, P.J., Wright, F., Sharma, S.K., Bolser, D., Bryan, G.J., Jones, J.D., Hein, I. 2012. Identification and localisation of the NB-LRR gene family within the potato genome. BMC Genomics 2012 13:75. (doi:10.1186/1471-2164-13-75)
- McNally, R.R., Toth, I.K., Cock, P.J.A., Pritchard, L., Hedley, P.E., Morris, J.A., Zhao, Y., Sundin, G.W. 2012 Genetic characterization of the HrpL regulon of the fire blight pathogen Erwinia amylovora reveals novel virulence factors. Mol Plant Pathol 13: 160–173. (doi:10.1111/j.1364-3703.2011.00738.x)
- Gilroy, E.M., Breen, S., Whisson, S.C., Squires, J., Hein, I., Kaczmarek, M., Turnbull, D., Boevink, P.C., Lokossou, A., Cano, L.M., Morales, J., Avrova, A.O., Pritchard, L., Randall, E., Lees, A., Govers, F., van West, P., Kamoun, S., Vleeshouwers, V.G., Cooke, D.E., Birch, P.R. 2011. Presence/absence, differential expression and sequence polymorphisms between PiAVR2 and PiAVR2-like in Phytophthora infestans determine virulence on R2 plants. New Phytologist 2011 191:3 763-776 (doi: 10.1111/j.1469-8137.2011.03736.x)
- Pritchard L., Birch P.R. 2011 A systems biology perspective on plant-microbe interactions: Biochemical and structural targets of pathogen effectors. Plant Science180: 584-603. doi:10.1016/j.plantsci.2010.12.008.
- Antunez-Lamas,M., Cabrera, E, Lopez-Solanilla, E., Solano, R., González-Melendi, P., Chico, J.M., Toth, I.K., Birch, P.R.J., Pritchard, L., Liu, H., and Rodriguez-Palenzuela, P. 2009. Bacterial chemoattraction towards jasmonate plays a role in the entry of Dickeya dadantii through wounded tissues. Molecular Microbiology 74(3), 662-671. (doi:10.1111/j.1365-2958.2009.06888.x)
- Haas, B.J., Kamoun, S., Zody, M.C., [+59 authors+] Pritchard, L. [+29 authors+] Birch, P.R.J., Whisson, S.C., Judelson, H.S. & Nusbaum, C. 2009. Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans. Nature 461, 393-398. (doi:10.1038/nature08358)
- Pritchard, L., Liu, H., Booth, C., Douglas, E., Francois, P., Schrenzel, J., Hedley, P., Birch, P.R.J. and Toth, I.K. 2009. Microarray comparative genomic hybridisation analysis incorporating genomic organisation, and application to enterobacterial plant pathogens. PLoS Computational Biology 5(8), e1000473.
- Birch, P.R.J., Armstrong, M.A., Bos, J., Boevink, P.C., Gilroy, E.M., Taylor, R.M., Wawra, S., Pritchard, L., Conti, L.., Ewan, R., Whisson, S.C., van West, P., Sadanandom, A., and Kamoun, S. 2009. Towards understanding the virulence functions of RXLR effectors of the oomycete plant pathogen Phytophthora infestans. Journal of Experimental Botany 60, 1133-1140. (doi:10.1093/jxb/ern353)
- Holden, N., Pritchard, L. and Toth, I.K.. 2008. Colonization outwith the colon:plants as an alternative environmental reservoir for human pathogenic enterobacteria. FEMS Microbiology Reviews 33, 689-703. (doi:10.1111/j.1574-6976.2008.00153.x)
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