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个人简介

2015-current: Senior Lecturer, School of BABS 2014-2015: NHMRC Postdoctoral Researcher, Peter Doherty Institute, University of Melbourne 2010-2014: Postdoctoral Researcher, Wellcome Centre for Cell Biology & The Roslin Institute, University of Edinburgh 2007-2010: Postdoctoral Researcher, Royal (Dick) School of Veterinary Studies, University of Edinburgh

研究领域

My lab has an ongoing interest in how complex genetic traits such as virulence are assembled and selected in bacterial pathogens. Transcriptional regulation of bacterial virulence Many bacterial pathogens, including Staphylococcus, Vibrio, Salmonella spp., and E. coli have acquired the genes for pathogenesis through horizontal gene transfer. A stark example of this is Enterohaemorhaggic E. coli (EHEC), which has obtained more than a fifth of its genome (and its ability to cause disease) through acquisition of mobile genetic elements (termed pathogenicity islands or PAIs). This suggests a level of ‘plug and play’ genetics and raises the question of how this assortment of genetic material is regulated and coordinated to allow a productive virulence program. By screening mutant libraries and analysing clinical isolates of EHEC we have identified a number of regulators acquired on PAIs that control virulence. A recent example is the prophage secretion regulator (Psr) family of transcriptional regulators that coordinates expression between independent, horizontally acquired PAIs. Psr encoding islands carry virulence proteins known as ‘effectors’ that are injected into host cells by the type 3 secretion system (T3SS). Psr was found to regulate T3SS through the acid stress response - encoded within the conserved ‘core’ genome. We speculate that coordination between the pathogenicity islands positively selects for effector secretion. Post-transcriptional regulation of bacterial virulence  Non-coding RNA regulation has come to the fore with the advent of RNA sequencing. It is now abundantly apparent that all forms of life transcribe RNAs that do not encode proteins (non-coding RNAs), but regulate cellular processes through a myriad of mechanisms. Bacterial pathogens produce hundreds of non-coding RNAs, however we have a poor understanding of the function of the majority of these RNAs. UV-crosslinking and deep sequencing protein-RNA complexes (CRAC or CLIP-Seq) is a powerful technique for identifying protein interaction sites on RNAs. We have used this technique to study interactions between the ncRNA chaperone, Hfq, and the transcriptome. Using this technique, we have demonstrated that the pathogenicity islands of EHEC are rich in a class of ncRNA, termed small RNA (sRNA), and have revealed a new mechanism of ncRNA regulation. Unusally short RNAs (50-60nt) were identified that control the activity of sRNAs (as opposed to mRNAs). This new class of sRNAs have been termed ‘anti-sRNA’. We have found that anti-sRNA are required for effective growth of EHEC in bovine mucus, the environmental reservoir of EHEC, and are investigating the mechanisms behind this growth defect. RNA has two particularly useful properties for gene regulation; it is able to adopt a huge variety of conformations that can respond to environmental cues (e.g. riboswitches and RNA thermometers), and make sequence-specific interactions with RNAs through (often limited) base pairing. We anticipate that the mechanisms adopted by ncRNAs to control gene expression in bacterial pathogens will be exceptionally diverse, and are using UV-crosslinking and deep sequencing techniques to study these processes.

近期论文

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Monk IR; Tree JJ; Howden BP; Stinear TP; Foster TJ, 2015, 'Complete bypass of restriction systems for major staphylococcus aureus lineages', mBio, vol. 6, no. 3, pp. 1 - 12, http://dx.doi.org/10.1128/mBio.00308-15 Tree JJ; Granneman S; McAteer SP; Tollervey D; Gally DL, 2014, 'Identification of Bacteriophage-Encoded Anti-sRNAs in Pathogenic Escherichia coli', Molecular Cell, vol. 55, no. 2, pp. 199 - 213, http://dx.doi.org/10.1016/j.molcel.2014.05.006 Flockhart AF; Tree JJ; Xu X; Karpiyevich M; McAteer SP; Rosenblum R; Shaw DJ; Low CJ; Best A; Gannon V; Laing C; Murphy KC; Leong JM; Schneiders T; La Ragione R; Gally DL, 2012, 'Identification of a novel prophage regulator in Escherichia coli controlling the expression of type III secretion', Molecular Microbiology, vol. 83, no. 1, pp. 208 - 223, http://dx.doi.org/10.1111/j.1365-2958.2011.07927.x Xu X; McAteer SP; Tree JJ; Shaw DJ; Wolfson EBK; Beatson SA; Roe AJ; Allison LJ; Chase-Topping ME; Mahajan A; Tozzoli R; Woolhouse MEJ; Morabito S; Gally DL, 2012, 'Lysogeny with Shiga toxin 2-encoding bacteriophages represses type III secretion in enterohemorrhagic Escherichia coli', PLoS Pathogens, vol. 8, no. 5, http://dx.doi.org/10.1371/journal.ppat.1002672 Tree JJ; Roe AJ; Flockhart A; Mcateer SP; Xu X; Shaw D; Mahajan A; Beatson SA; Best A; Lotz S; Woodward MJ; La Ragione R; Murphy KC; Leong JM; Gally DL, 2011, 'Transcriptional regulators of the GAD acid stress island are carried by effector protein-encoding prophages and indirectly control type III secretion in enterohemorrhagic Escherichia coli O157:H7', Molecular Microbiology, vol. 80, no. 5, pp. 1349 - 1365, http://dx.doi.org/10.1111/j.1365-2958.2011.07650.x Wang D; Zetterström CE; Gabrielsen M; Beckham KSH; Tree JJ; Macdonald SE; Byron O; Mitchell TJ; Gally DL; Herzyk P; Mahajan A; Uvell H; Burchmore R; Smith BO; Elofsson M; Roe AJ, 2011, 'Identification of bacterial target proteins for the salicylidene acylhydrazide Class of virulence-blocking compounds', Journal of Biological Chemistry, vol. 286, no. 34, pp. 29922 - 29931, http://dx.doi.org/10.1074/jbc.M111.233858 Tahoun A; Siszler G; Spears K; McAteer S; Tree J; Paxton E; Gillespie TL; Martinez-Argudo I; Jepson MA; Shaw DJ; Koegl M; Haas J; Gally DL; Mahajan A, 2011, 'Comparative analysis of EspF variants in inhibition of Escherichia coli phagocytosis by macrophages and inhibition of E. Coli translocation through human- and bovine-derived M cells', Infection and Immunity, vol. 79, no. 11, pp. 4716 - 4729, http://dx.doi.org/10.1128/IAI.00023-11 Bail J; McAteer SP; Paxton E; Mahajan A; Gally DL; Tree JJ, 2011, 'Screening of an E. Coli O157: H7 bacterial artificial chromosome library by comparative genomic hybridization to identify genomic regions contributing to growth in bovine gastrointestinal mucus and ep', Frontiers in Microbiology, vol. 2, no. AUG, http://dx.doi.org/10.3389/fmicb.2011.00168 Achard MES; Tree JJ; Holden JA; Simpfendorfer KR; Wijburg OLC; Strugnell RA; Schembri MA; Sweet MJ; Jennings MP; McEwan AG, 2010, 'The multi-copper-ion oxidase CueO of Salmonella enterica serovar typhimurium is required for systemic virulence', Infection and Immunity, vol. 78, no. 5, pp. 2312 - 2319, http://dx.doi.org/10.1128/IAI.01208-09 Allsopp LP; Totsika M; Tree JJ; Ulett GC; Mabbett AN; Wells TJ; Kobe B; Beatson SA; Schembri MA, 2010, 'UpaH is a newly identified autotransporter protein that contributes to biofilm formation and bladder colonization by uropathogenic Escherichia coli CFT073', Infection and Immunity, vol. 78, no. 4, pp. 1659 - 1669, http://dx.doi.org/10.1128/IAI.01010-09 Mahajan A; Currie CG; Mackie S; Tree J; Mcateer S; Mckendrick I; Mcneilly TN; Roe A; La Ragione RM; Woodward MJ; Gally DL; Smith DGE, 2009, 'An investigation of the expression and adhesin function of H7 flagella in the interaction of Escherichia coli O157: H7 with bovine intestinal epithelium', Cellular Microbiology, vol. 11, no. 1, pp. 121 - 137, http://dx.doi.org/10.1111/j.1462-5822.2008.01244.x Tree JJ; Wolfson EB; Wang D; Roe AJ; Gally DL, 2009, 'Controlling injection: regulation of type III secretion in enterohaemorrhagic Escherichia coli', Trends in Microbiology, vol. 17, no. 8, pp. 361 - 370, http://dx.doi.org/10.1016/j.tim.2009.06.001 Tree JJ; Wang D; McInally C; Mahajan A; Layton A; Houghton I; Elofsson M; Stevens MP; Gally DL; Roe AJ, 2009, 'Characterization of the effects of salicylidene acylhydrazide compounds on type III secretion in Escherichia coli O157:H7', Infection and Immunity, vol. 77, no. 10, pp. 4209 - 4220, http://dx.doi.org/10.1128/IAI.00562-09 MABBETT A; ULETT G; WATTS R; TREE J; TOTSIKA M; ONG C; WOOD J; MONAGHAN W; LOOKE D; NIMMO G, 2009, 'Virulence properties of asymptomatic bacteriuria Escherichia coli', International Journal of Medical Microbiology, vol. 299, no. 1, pp. 53 - 63, http://dx.doi.org/10.1016/j.ijmm.2008.06.003 Tree JJ; Ulett GC; Ong C-LY; Trott DJ; McEwan AG; Schembri MA, 2008, 'Trade-Off between Iron Uptake and Protection against Oxidative Stress: Deletion of cueO Promotes Uropathogenic Escherichia coli Virulence in a Mouse Model of Urinary Tract Infection', Journal of Bacteriology, vol. 190, no. 20, pp. 6909 - 6912, http://dx.doi.org/10.1128/JB.00451-08 Wells TJ; Tree JJ; Ulett GC; Schembri MA, 2007, 'Autotransporter proteins: novel targets at the bacterial cell surface', FEMS Microbiology Letters, vol. 274, no. 2, pp. 163 - 172, http://dx.doi.org/10.1111/j.1574-6968.2007.00833.x Tree JJ; Ulett GC; Hobman JL; Constantinidou C; Brown NL; Kershaw C; Schembri MA; Jennings MP; McEwan AG, 2007, 'The multicopper oxidase (CueO) and cell aggregation in Escherichia coli', Environmental Microbiology, vol. 9, no. 8, pp. 2110 - 2116, http://dx.doi.org/10.1111/j.1462-2920.2007.01320.x Tree JJ; Kidd SP; Jennings MP; McEwan AG, 2005, 'Copper sensitivity of cueO mutants of Escherichia coli K-12 and the biochemical suppression of this phenotype', Biochemical and Biophysical Research Communications, vol. 328, no. 4, pp. 1205 - 1210, http://dx.doi.org/10.1016/j.bbrc.2005.01.084

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