Current Research

• The Pectobacterium atrosepticum:potato pathosystem.
• The Phytophthora infestans:potato pathosystem.
• Comparative genomics of plant pathogens.
• Systems biology of pathogen:host interactions.

Research History

• Bacterial Comparative Genomics. I arrived at SCRI in 2003, just prior to the complete sequencing of Pectobacterium atrosepticum (Pba; formerly Erwinia carotovora subsp. atroseptica). I worked with the Toth group to initiate and complete large-scale comparative genomic analyses of this organism against over 200 other bacterial genome sequences, establishing the strong influence of horizontal gene transfer on this organism’s adaptation to its environment, and on development of its mechanisms of pathogenicity (Bell et al., 2004). This work has since been extended to the full set of sequenced bacterial genomes, though we concentrate our efforts largely on the plant pathogenic bacteria (Toth et al., 2006). These comparative genomic analyses of Pba and its bacterial relatives have been used to elucidate the evolutionary history of this organism and its genetic relationship with other plant and animal pathogens, leading to work with a number of collaborators in the UK and abroad.
• As part of this work, I developed the Python library GenomeDiagram for comparative genomic analyses and visualisation of the resulting large datasets. The GenomeDiagram software was announced in Pritchard et al. (2006). Images generated by GenomeDiagram led to collaboration (with Ian Toth) with Professor Elaine Shemilt at the Duncan of Jordanstone College of Art and Design. Exhibitions of the resulting print, music and computer animation works have been displayed at the Biopolis centre in Singapore, at the Dundee Contemporary Arts centre, and reported in The Scotsman. This work has also featured many times in newsletters and other literature from the University of Dundee.
• Oomycete Genome Comparisons and Annotation. Shortly after arriving at SCRI, I annotated several Phytophthora infestans and Hyaloperonospora parasitica BACs containing avirulence loci, and performed comparative genomic analyses on these in relation to the sequenced genomes of Phytophthora sojae, and Phytophthora ramorum. This work, with the Birch and Whisson groups, was a contribution towards the identification and evolutionary characterisation of the first P. infestans avirulence effector to be characterised (Armstrong et al., 2005).
• I have since, with the Whisson and Birch groups, annotated a number of other sequence families in the P. infestans genome, including fifteen families of short interspersed elements (SINEs) (Whisson et al., 2005), the Pinci1 family of infection stage-specific noncoding sequences (Avrova et al., 2007), and over 100 candidate translocated virulence effectors (Whisson et al., in press).
• Protein Structure-Function Relationships. Protein functions are determined by the interactions they can make with other chemical moieties. These interactions are in turn determined by the shapes into which their amino-acid chains can fold, and these shapes are (mostly) determined by the sequence of amino acids on that chain. I began my research career with my Ph.D. at the University of Strathclyde under the supervision of Dr Mark Dufton, where I worked from 1996-1999, primarily on structure-function relationships of protein components of snake venom. I applied Evolutionary Trace and covariation analyses to several families of snake venom toxins (Pritchard and Dufton, 1999; Pritchard et al., 2001) and co-developed the SID structural analysis (Pritchard et al., 2003). I also developed a model of protein functional evolution analogous to memory recall in a Hopfield neural network (Pritchard and Dufton, 2000).
• Systems Biology. From 1999-2003 I was a postdoc in the Kell group at the University of Wales, Aberystwyth, where I carried out ODE modelling of metabolic processes. I used evolutionary computing to parameter fit ODE models of yeast glycolysis to experimentally-determined metabolic data. I then explored the fitted models under a range of further parameter settings corresponding to a number of experimental and/or environmental conditions. This work established the existence of a number of modes of metabolic flux control in yeast glycolysis, and the conditions under which they operated (Pritchard and Kell, 2002). I also extended a model of the polymerase chain reaction (PCR) in support of directed evolution experiments (Pritchard et al., 2005).
• My current interests in systems biology centre on the elucidation and characterisation of mechanisms of virulence in plant pathogens, and of the response to pathogens in the host plant (Birch et al., 2006). I supervise a University of Dundee PhD student on a SEERAD FF systems biology grant to evaluate methods for the identification of regulatory binding sites in Pba, and to map their locations and predict and reconstruct the corresponding regulatory networks. As part of this work I designed microarrays for bacterial potato pathogens, and for potato stress and disease response, which also find use with our collaborators (Ravirala et al., 2007).
• My ambitions in systems biology require ‘closing the loop’: ensuring that theoretically or mathematically-derived hypotheses are tested experimentally. In the context of systems biology, SCRI is uniquely placed to exploit extensive scientific knowledge and expertise, plant science/growing facilities, and access to collections of crops and pathogens, not only to ‘close the loop’, but to do so in a way that delivers meaningful end products for stakeholders and the community.

Recent Publications

• 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)
• Birch, P.R.J., Boevink, P.C., Gilroy, E.M., Hein, I., Pritchard, L., and Whisson, S.C. 2008. Oomycete RXLR effectors: delivery, functional redundancy and durable disease resistance. Current Opinion in Plant Biology 11, 373-379. (doi:10.1016/j.pbi.2008.04.005)
• Liu, H., Coulthurst, S.J., Pritchard L., Hedley, P.E., Ravensdale, M., Humphris, S., Burr, T., Takle, G., Brurberg, M-B., Birch, P.R.J., Salmond, G.P.C., and Toth, I.K. 2008. Quorum Sensing Coordinates Brute Force and Stealth Modes of Infection in the Plant Pathogen Pectobacterium atrosepticum. PLoS Pathogens 4, e1000093. (doi:10.1371/journal.ppat.1000093)
• Whisson, S.C., Boevink, P.C., Moleleki, L. , Avrova,  A.O., Morales, J.G., Gilroy, E.M., Armstrong,  M.R.,  Grouffaud, S., van West, P., Chapman, S., Hein, I., Toth, I.K., Pritchard, L. and Birch, P.R.J. 2007. A translocation signal for delivery of oomycete effector proteins into host plant cells. Nature 450, 115-118. (doi:10.1038/nature06203)
• Gilroy, E.M., Hein, I., van der Hoorn, R., Boevink, P.C., Venter, E., McLellan, H., Kaffarnik, F., Hrubikova, K., Shaw, J., Holeva, M., López, E.C., Borras-Hidalgo, O., Pritchard, L., Loake, G.J., Lacomme, C. and  Birch, P.R.J. 2007.  Involvement of cathepsin B in the plant disease resistance hypersensitive response.  The Plant Journal 52, 1-13. (doi:10.1111/j.1365-313X.2007.03226.x)
• Avrova, A.O., Whisson, S.C., Pritchard, L., Venter, E., De Luca, S., Hein, I. and Birch, P.R.J. 2007. A novel, non-protein coding infection-specific gene family is clustered throughout the genome of Phytophthora infestans. Microbiology 153, 747-759. (doi:10.1099/mic.0.2006/002220-0)
• Ravirala, R.S., Barabote,  R.D., Wheeler, D.M., Reverchon, S., Tatum, O., Malouf, J., Liu, H., Pritchard,  L., Hedley, P.E., Birch, P.R.J., Toth, I.K., Payton, P. and San Francisco, M.J.D. 2007. Efflux Pump Gene Expression in Erwinia Chrysanthemi is induced by Exposure to Phenolic Acids. Molecular Plant-Microbe Interactions 20, 313-320. (doi:10.1094/MPMI-20-3-0313)
• Kikuchi, T., Aikawa, T., Kosaka, H., Pritchard, L., Ogura, N. and Jones, J.T. 2007. EST analysis of the pine wood nematode Bursaphelenchus xylophilus and B. mucronatus. Molecular and Biochemical Parasitology 155, 9-17. (doi: 10.1016/j.molbiopara.2007.05.002)
• Toth, I.K., Pritchard, L. and Birch, P.R.J. 2006. Comparative Genomics Reveals What Makes an Enterobacterial Plant Pathogen. Annual Review of Phytopathology 44, 305-336. (doi:10.1146/annurev.phyto.44.070505.143444)
• Toth, I.K., Moleleki, L., Pritchard, L., Liu, H., Humphris, S., Hyman, L., Axelsen, G.W., Brurberg, M.B., Ravensdale, M., Gilroy, E. and Birch, P.R.J. 2006. Erwiniae: Genomics and the Secret Life of a Plant Pathogen. In Bailey, M.J. et al. eds. Microbial Ecology of Aerial Plant Surfaces, pp191-201; CABI Publishing; ISBN: 978-1-84593-061-5.
• Pritchard, L., White, J.A., Birch, P.R.J., Toth, I.K. 2006. GenomeDiagram: A Python Package for the Visualisation of Large-Scale Genomic Data. Bioinformatics 22, 616-617. (doi:10.1093/bioinformatics/btk021)
• Birch, P.R.J., Rehmany, A.P., Pritchard, L., Kamoun, S. and Beynon, J.L. 2006. Trafficking arms: oomycete effectors enter host plant cells. Trends in Microbiology 14, 8-11. (doi:10.1016/j.tim.2005.11.007)
• Armstrong, M.R., Whisson, S.C., Pritchard, L., Bos, J.I.B., Venter, E., Avrova, A.O., Rehmany, A.P., Böhme, U., Brooks, K., Cherevach, I., Hamlin, N., White, B., Fraser, A., Lord, A., Quail, M.A., Churcher, C.,  Hall, N., Berriman, M., Huang, S., Kamoun, S., Beynon, J.L. and Birch, P.R.J. 2005. An ancestral oomycete locus contains late blight avirulence gene Avr3a, encoding a protein that is recognized in the host cytoplasm . Proceedings of the National Academy of Sciences, USA 102, 7766-7771. (doi:10.1073/pnas.0500113102)
• Pritchard, L., Corne, D.W., Kell, D.B., Rowland, J.J. and Winson, M.K. 2005. A general model of error-prone PCR. Journal of Theoretical Biology 234, 497-509. (doi:10.1016/j.jtbi.2004.12.005)
• Whisson, S.C., Avrova, A.O., Lavrova, O., Pritchard, L. 2005. Families of short interspersed elements in the genome of the oomycete plant pathogen, Phytophthora infestans. Fungal Genetics and Biology 42, 351-365. (doi:10.1016/j.fgb.2005.01.004)
• Bell, K.S., Sebaihia, M., Pritchard, L., Holden, M.T.G., Hyman, L.J., Holeva, M.C., Thomson, N.R., Bentley, S.D., Churcher, L.J.C., Mungall, K., Atkin, R., Bason, N., Brooks, K., Chillingworth, T., Clark, K., Doggett, J., Fraser, A., Hance, Z., Hauser, H., Jagels, K., Moule, S., Norbertczak, H., Ormond, D., Price,  C., Quail, M.A., Sanders, M., Walker, D., Whitehead, S., Salmond, G.P.C., Birch, P.R.J., Parkhill,  J. and Toth, I.K. 2004. Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors. Proceedings of the National Academy of Sciences, USA 101, 11105-11110. (doi:10.1073/pnas.0402424101)

Posters

(View all posters)

Attachment	Size
Identification Of Novel Erwinia Genes Involved In Disease	133.37 KB
Post-Genomic Analysis of Erwinia Carotovora Virulence Responses in In Vitro and In Planta Environments	119.48 KB
Expression profiles of RXLR motif-containing sequences during Phytophthora infestans-potato interactions	1.4 MB
A step closer to blackleg control: Genomics opens our eyes to the true nature of Erwinia and its interaction with plants	212.62 KB
Genomics approaches uncover an alternative life-style of the plant pathogen Pectobacterium atrosepticum	210.23 KB
A whole genome transcriptomics approach to determine the quorum sensing regulon of Pectobacterium atrosepticum during infection	176.37 KB
Comparative Genomic Analysis of Erwinia carotovora subsp atroseptica: Evidence For Extensive Horizontal Gene Transfer with Plant Associated Bacteria	613.23 KB
Prediction of transcription factor binding sites in bacterial genomes: case study with Pectobacterium atrosepticum	405.75 KB
Development of a Computational Pipeline For Automated Prediction of Bacterial Transcription Factor Binding Sites	1.39 MB
Functional characterization of the RxLR-EER translocation signal for delivery of oomycete effector proteins into host plant cells	162.54 KB
Methods to investigate interactions between human pathogenic enterobacteria and plant hosts	235.09 KB
Comparative and functional genomics identifies major differences between genomic islands in soft rotting enterobacterial plant pathogens	414.25 KB
Bioinformatic Analysis of Palindromes in Bacterial Genome Sequences	412.45 KB
Exploiting the Phytophthora infestans genome to determine targets for sustainable potato protection	597.58 KB