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Dr Giselda Bucca

Research Fellow

Email:
Phone: Work: 01483 68 6498
Room no: 14 AX 02

Office hours

By appointment

Further information

Research Interests

  •  Global analysis of gene expression in bacteria and human tissues
  •  Transcriptional and translational control of stress responses in Actinimycetes
  •  Role of non-coding RNAs

My research interests are in the broad area of gene regulation and functional genomics. I am part of the Functional Genomics group of Prof Colin Smith. Much of my research exploits the use of DNA microarrays to (a) study Streptomyces biology, (b) analyse human cancers and (c) study the functional genomics of sleep and sleep deprivation.
 

Streptomyces coelicolor microarrays .

We have developed, in collaboration with Oxford Gene Technology (Oxford, UK), S. coelicolor high density IJISS microarrays covering both intergenic regions and coding regions allowing the simultaneous analysis of ChIP-on-chip and gene expression data on the same platform. A number of different collaborative projects covering different aspects of Streptomyces biology are under way in our group. These include: genome-wide transcriptional and translational analysis of stress responses (in particular heat shock) in Streptomyces, transcriptional analysis and ChIP-on-chip analysis of global regulators in Streptomyces including DasR and ROK7B7 (in collaboration with Prof. G.van Wezel, University of Leiden, Netherlands) and ChIP-on-chip analysis of RNA Polymerase distribution in different stages of the Streptomyces life cycle (in collaboration with Prof. D. Hodgson, University of Warwick, UK). Other areas of current interest in our group are the investigation, at the transcriptional level, of phosphate regulation of antibiotic production mediated by PhoP global regulator and the characterization of the networks under the genetic control of the AbsA1/AbsA2 two-component system and its interplay with the CdaR regulon. Both AbsA2 and CdaR are global regulators encoded by the cda antibiotic cluster of S. coelicolor. Other regulators under study include the atypical response regulator AbrC3 in collaboration with Dr M. Diaz and Dr R. Santamaria, University of Salamanca, Spain


We are also currently involved in a research project focussing on gene expression profiling of human metastatic colon cancer in the liver and in the detection of circulating tumor cells in blood during chemotherapy treatment of human metastatic colon cancer patients in collaboration with Prof. N. Karanjia (Royal Surrey County Hospital, Guildford, UK). Additionally, we are part of a multidisciplinary team investigating genome-wide expression in human and mouse variants of the PER3 VNTR polymorphism (in collaboration with Prof. D.J. Dijk and others, Surrey Sleep Research Centre, University of Surrey, UK).
 

One of my roles within the FHMS Core Microarray Facility is to provide advice and practical training in the field of DNA microarray-based analysis of gene expression.

Useful links: http://unis.streptobase.org





 

Publications

Highlights

  • Allenby NE, Laing E, Bucca G, Kierzek AM, Smith CP. (2012) 'Diverse control of metabolism and other cellular processes in Streptomyces coelicolor by the PhoP transcription factor: genome-wide identification of in vivo targets.'. Oxford University Press Nucleic Acids Res,
    doi: 10.1093/nar/gks766
    Full text is available at: http://epubs.surrey.ac.uk/725768/

    Abstract

    Streptomycetes sense and respond to the stress of phosphate starvation via the two-component PhoR-PhoP signal transduction system. To identify the in vivo targets of PhoP we have undertaken a chromatin-immunoprecipitation-on-microarray analysis of wild-type and phoP mutant cultures and, in parallel, have quantified their transcriptomes. Most (ca. 80%) of the previously in vitro characterized PhoP targets were identified in this study among several hundred other putative novel PhoP targets. In addition to activating genes for phosphate scavenging systems PhoP was shown to target two gene clusters for cell wall/extracellular polymer biosynthesis. Furthermore PhoP was found to repress an unprecedented range of pathways upon entering phosphate limitation including nitrogen assimilation, oxidative phosphorylation, nucleotide biosynthesis and glycogen catabolism. Moreover, PhoP was shown to target many key genes involved in antibiotic production and morphological differentiation, including afsS, atrA, bldA, bldC, bldD, bldK, bldM, cdaR, cdgA, cdgB and scbR-scbA. Intriguingly, in the PhoP-dependent cpk polyketide gene cluster, PhoP accumulates substantially at three specific sites within the giant polyketide synthase-encoding genes. This study suggests that, following phosphate limitation, Streptomyces coelicolor PhoP functions as a 'master' regulator, suppressing central metabolism, secondary metabolism and developmental pathways until sufficient phosphate is salvaged to support further growth and, ultimately, morphological development.

  • Lewis RA, Laing E, Allenby N, Bucca G, Brenner V, Harrison M, Kierzek AM, Smith CP. (2010) 'Metabolic and evolutionary insights into the closely-related species Streptomyces coelicolor and Streptomyces lividans deduced from high-resolution comparative genomic hybridization.'. BMC Genomics, England: 11
    doi: 10.1186/1471-2164-11-682
    Full text is available at: http://epubs.surrey.ac.uk/203299/

    Abstract

    Whilst being closely related to the model actinomycete Streptomyces coelicolor A3(2), S. lividans 66 differs from it in several significant and phenotypically observable ways, including antibiotic production. Previous comparative gene hybridization studies investigating such differences have used low-density (one probe per gene) PCR-based spotted arrays. Here we use new experimentally optimised 104,000 × 60-mer probe arrays to characterize in detail the genomic differences between wild-type S. lividans 66, a derivative industrial strain, TK24, and S. coelicolor M145.

  • Salerno P, Larsson J, Bucca G, Laing E, Smith CP, Flardh K. (2009) 'One of the Two Genes Encoding Nucleoid-Associated HU Proteins in Streptomyces coelicolor Is Developmentally Regulated and Specifically Involved in Spore Maturation'. AMER SOC MICROBIOLOGY JOURNAL OF BACTERIOLOGY, 191 (21), pp. 6489-6500.
    doi: 10.1128/JB.00709-09
  • de Jong W, Manteca A, Sanchez J, Bucca G, Smith CP, Dijkhuizen L, Claessen D, Wosten HAB. (2009) 'NepA is a structural cell wall protein involved in maintenance of spore dormancy in Streptomyces coelicolor'. WILEY-BLACKWELL PUBLISHING, INC MOLECULAR MICROBIOLOGY, 71 (6), pp. 1591-1603.
    doi: 10.1111/j.1365-2958.2009.06633.x
  • Bucca G, Laing E, Mersinias V, Allenby N, Hurd D, Holdstock J, Brenner V, Harrison M, Smith CP. (2009) 'Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon'. BIOMED CENTRAL LTD GENOME BIOLOGY, 10 (1) Article number ARTN R5
    doi: 10.1186/gb-2009-10-1-r5
    Full text is available at: http://epubs.surrey.ac.uk/203295/
  • Hesketh A, Bucca G, Laing E, Flett F, Hotchkiss G, Smith CP, Chater KF. (2007) 'New pleiotropic effects of eliminating a rare tRNA from Streptomyces coelicolor, revealed by combined proteomic and transcriptomic analysis of liquid cultures'. BIOMED CENTRAL LTD BMC GENOMICS, 8 Article number ARTN 261
    doi: 10.1186/1471-2164-8-261
    Full text is available at: http://epubs.surrey.ac.uk/203300/
  • Bucca G, Brassington AME, Hotchkiss G, Mersinias V, Smith CP. (2003) 'Negative feedback regulation of dnaK, clpB and lon expression by the DnaK chaperone machine in Streptomyces coelicolor, identified by transcriptome and in vivo DnaK-depletion analysis'. BLACKWELL PUBLISHING LTD MOLECULAR MICROBIOLOGY, 50 (1), pp. 153-166.
    doi: 10.1046/j.1365-2958.2003.03696.x

Journal articles

  • Swiatek MA, Gubbens J, Bucca G, Song E, Yang YH, Laing E, Kim BG, Smith CP, van Wezel GP. (2013) 'The ROK-family regulator Rok7B7 pleiotropicaly affects xylose utilization, carbon catabolite repression and antibiotic production in Streptomyces coelicolor.'. J Bacteriol,
    doi: 10.1128/JB.02191-12
  • Allenby NE, Laing E, Bucca G, Kierzek AM, Smith CP. (2012) 'Diverse control of metabolism and other cellular processes in Streptomyces coelicolor by the PhoP transcription factor: genome-wide identification of in vivo targets.'. Oxford University Press Nucleic Acids Res,
    doi: 10.1093/nar/gks766
    Full text is available at: http://epubs.surrey.ac.uk/725768/

    Abstract

    Streptomycetes sense and respond to the stress of phosphate starvation via the two-component PhoR-PhoP signal transduction system. To identify the in vivo targets of PhoP we have undertaken a chromatin-immunoprecipitation-on-microarray analysis of wild-type and phoP mutant cultures and, in parallel, have quantified their transcriptomes. Most (ca. 80%) of the previously in vitro characterized PhoP targets were identified in this study among several hundred other putative novel PhoP targets. In addition to activating genes for phosphate scavenging systems PhoP was shown to target two gene clusters for cell wall/extracellular polymer biosynthesis. Furthermore PhoP was found to repress an unprecedented range of pathways upon entering phosphate limitation including nitrogen assimilation, oxidative phosphorylation, nucleotide biosynthesis and glycogen catabolism. Moreover, PhoP was shown to target many key genes involved in antibiotic production and morphological differentiation, including afsS, atrA, bldA, bldC, bldD, bldK, bldM, cdaR, cdgA, cdgB and scbR-scbA. Intriguingly, in the PhoP-dependent cpk polyketide gene cluster, PhoP accumulates substantially at three specific sites within the giant polyketide synthase-encoding genes. This study suggests that, following phosphate limitation, Streptomyces coelicolor PhoP functions as a 'master' regulator, suppressing central metabolism, secondary metabolism and developmental pathways until sufficient phosphate is salvaged to support further growth and, ultimately, morphological development.

  • Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, Chope G, Hyppönen E, Berry J, Vieth R, Lanham-New S. (2012) 'Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis.'. American Society for Nutrition Am J Clin Nutr, United States: 95 (6), pp. 1357-1364.
    doi: 10.3945/ajcn.111.031070
    Full text is available at: http://epubs.surrey.ac.uk/725769/

    Abstract

    Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D(2) and D(3) in the raising of serum 25-hydroxyvitamin D [25(OH)D].

  • Lewis RA, Shahi SK, Laing E, Bucca G, Efthimiou G, Bushell M, Smith CP. (2011) 'Genome-wide transcriptomic analysis of the response to nitrogen limitation in Streptomyces coelicolor A3(2).'. BMC Res Notes, England: 4
    doi: 10.1186/1756-0500-4-78
    Full text is available at: http://epubs.surrey.ac.uk/203297/
  • Lewis RA, Laing E, Allenby N, Bucca G, Brenner V, Harrison M, Kierzek AM, Smith CP. (2010) 'Metabolic and evolutionary insights into the closely-related species Streptomyces coelicolor and Streptomyces lividans deduced from high-resolution comparative genomic hybridization.'. BMC Genomics, England: 11
    doi: 10.1186/1471-2164-11-682
    Full text is available at: http://epubs.surrey.ac.uk/203299/

    Abstract

    Whilst being closely related to the model actinomycete Streptomyces coelicolor A3(2), S. lividans 66 differs from it in several significant and phenotypically observable ways, including antibiotic production. Previous comparative gene hybridization studies investigating such differences have used low-density (one probe per gene) PCR-based spotted arrays. Here we use new experimentally optimised 104,000 × 60-mer probe arrays to characterize in detail the genomic differences between wild-type S. lividans 66, a derivative industrial strain, TK24, and S. coelicolor M145.

  • Salerno P, Larsson J, Bucca G, Laing E, Smith CP, Flardh K. (2009) 'One of the Two Genes Encoding Nucleoid-Associated HU Proteins in Streptomyces coelicolor Is Developmentally Regulated and Specifically Involved in Spore Maturation'. AMER SOC MICROBIOLOGY JOURNAL OF BACTERIOLOGY, 191 (21), pp. 6489-6500.
    doi: 10.1128/JB.00709-09
  • de Jong W, Manteca A, Sanchez J, Bucca G, Smith CP, Dijkhuizen L, Claessen D, Wosten HAB. (2009) 'NepA is a structural cell wall protein involved in maintenance of spore dormancy in Streptomyces coelicolor'. WILEY-BLACKWELL PUBLISHING, INC MOLECULAR MICROBIOLOGY, 71 (6), pp. 1591-1603.
    doi: 10.1111/j.1365-2958.2009.06633.x
  • Sooriakumaran P, Macanas-Pirard P, Bucca G, Henderson A, Langley SE, Laing RW, Smith CP, Laing EE, Coley HM. (2009) 'A gene expression profiling approach assessing celecoxib in a randomized controlled trial in prostate cancer.'. Cancer Genomics Proteomics, Greece: 6 (2), pp. 93-99.
    Full text is available at: http://epubs.surrey.ac.uk/203293/

    Abstract

    We performed a pilot study, looking at the COX-2 inhibitor celecoxib, on newly diagnosed prostate cancer patients in the neo-adjuvant setting using DNA microarray analysis.

  • Bucca G, Laing E, Mersinias V, Allenby N, Hurd D, Holdstock J, Brenner V, Harrison M, Smith CP. (2009) 'Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon'. BIOMED CENTRAL LTD GENOME BIOLOGY, 10 (1) Article number ARTN R5
    doi: 10.1186/gb-2009-10-1-r5
    Full text is available at: http://epubs.surrey.ac.uk/203295/
  • Hesketh A, Bucca G, Laing E, Flett F, Hotchkiss G, Smith CP, Chater KF. (2007) 'New pleiotropic effects of eliminating a rare tRNA from Streptomyces coelicolor, revealed by combined proteomic and transcriptomic analysis of liquid cultures'. BIOMED CENTRAL LTD BMC GENOMICS, 8 Article number ARTN 261
    doi: 10.1186/1471-2164-8-261
    Full text is available at: http://epubs.surrey.ac.uk/203300/
  • Takano E, Kinoshita H, Mersinias V, Bucca G, Hotchkiss G, Nihira T, Smith CP, Bibb M, Wohlleben W, Chater K. (2005) 'A bacterial hormone (the SCB1) directly controls the expression of a pathway-specific regulatory gene in the cryptic type I polyketide biosynthetic gene cluster of Streptomyces coelicolor'. BLACKWELL PUBLISHING LTD MOLECULAR MICROBIOLOGY, 56 (2), pp. 465-479.
    doi: 10.1111/j.1365-2958.2005.04543.x
  • Vinciotti V, Khanin R, D'Alimonte D, Liu X, Cattini N, Hotchkiss G, Bucca G, de Jesus O, Rasaiyaah J, Smith CP, Kellam P, Wit E. (2005) 'An experimental evaluation of a loop versus a reference design for two-channel microarrays'. OXFORD UNIV PRESS BIOINFORMATICS, 21 (4), pp. 492-501.
    doi: 10.1093/bioinformatics/bti022
  • Bucca G, Brassington AME, Hotchkiss G, Mersinias V, Smith CP. (2003) 'Negative feedback regulation of dnaK, clpB and lon expression by the DnaK chaperone machine in Streptomyces coelicolor, identified by transcriptome and in vivo DnaK-depletion analysis'. BLACKWELL PUBLISHING LTD MOLECULAR MICROBIOLOGY, 50 (1), pp. 153-166.
    doi: 10.1046/j.1365-2958.2003.03696.x
  • Chater KF, Bucca G, Dyson P, Fowler K, Gust B, Herron P, Hesketh A, Hotchkiss G, Kieser T, Mersinias V, Smith CP. (2002) 'Streptomyces coelicolor A3(2): from genome sequence to function'. ACADEMIC PRESS INC FUNCTIONAL MICROBIAL GENOMICS, 33, pp. 321-336.
  • Bucca G, Brassington AME, Schonfeld HJ, Smith CP. (2000) 'The HspR regulon of Streptomyces coelicolor: a role for the DnaK chaperone as a transcriptional co-repressor'. BLACKWELL SCIENCE LTD MOLECULAR MICROBIOLOGY, 38 (5), pp. 1093-1103.
    doi: 10.1046/j.1365-2958.2000.02194.x
  • Bucca G, Hindle Z, Smith CP. (1997) 'Regulation of the dnaK operon of Streptomyces coelicolor A3(2) is governed by HspR, an autoregulatory repressor protein'. AMER SOC MICROBIOLOGY JOURNAL OF BACTERIOLOGY, 179 (19), pp. 5999-6004.
  • BUCCA G, FERINA G, PUGLIA AM, SMITH CP. (1995) 'THE DNAK OPERON OF STREPTOMYCES-COELICOLOR ENCODES A NOVEL HEAT-SHOCK PROTEIN WHICH BINDS TO THE PROMOTER REGION OF THE OPERON'. BLACKWELL SCIENCE LTD MOLECULAR MICROBIOLOGY, 17 (4), pp. 663-674.
    doi: 10.1111/j.1365-2958.1995.mmi_17040663.x
  • BUCCA G, SMITH CP, ALBERTI M, SEIDITA G, PASSANTINO R, PUGLIA AM. (1993) 'CLONING AND SEQUENCING OF THE DNAK REGION OF STREPTOMYCES-COELICOLOR A3(2)'. ELSEVIER SCIENCE BV GENE, 130 (1), pp. 141-144.
    doi: 10.1016/0378-1119(93)90358-A
  • MAGRIN S, CRAXI A, FABIANO C, FIORENTINO G, MARINO L, ALMASIO P, PINZELLO GB, PALAZZO U, VITALE M, MAGGIO A, BUCCA G, GIANGUZZA F, SHYAMALA V, HAN JH, PAGLIARO L. (1992) 'SERUM HEPATITIS-C VIRUS (HCV)-RNA AND RESPONSE TO ALPHA-INTERFERON IN ANTI-HCV POSITIVE CHRONIC HEPATITIS'. WILEY-LISS JOURNAL OF MEDICAL VIROLOGY, 38 (3), pp. 200-206.
    doi: 10.1002/jmv.1890380309
  • BUCCA G, SEIDITA G, ALBERTI M, MISURACA F, PUGLIA AM. (1988) 'IDENTIFICATION AND ISOLATION OF STREPTOMYCES-COELICOLOR A3(2) HSP 70 GENE'. BLACKWELL SCIENCE LTD HEREDITY, 61, pp. 310-310.

Conference papers

  • Lordan J, Karanjia N, Bucca G, Laing E, Smith C. (2010) 'Prospective analysis of the gene expression signature of peri-metastasis 'halo' tissue following neo-adjuvant chemotherapy-induced tumour reduction of colorectal liver metastasis'. WILEY-BLACKWELL BRITISH JOURNAL OF SURGERY, Liverpool, ENGLAND: Electronic Poster of Distinction in Association-of-Surgeons-of-Great-Britain-and-Ireland-International-Surgical-Congress 97, pp. 61-62.
  • Sooriakumaran P, Laing R, Macanas-Pirard P, Coley H, Fox S, Bucca G, Lovell D, Henderson A, Smith C, Eden C, Miller P, Langley S. (2007) 'A blinded, randomized controlled trial of neo-adjuvant celecoxib in patients with cT1-2 prostate cancer'. ELSEVIER SCIENCE INC JOURNAL OF UROLOGY, Anaheim, CA: 102nd Annual Meeting of the American-Urological-Association 177 (4), pp. 380-380.
  • Sooriakumaran P, Macanas-Pirard P, Fox S, Coley H, Bucca G, Lovell D, Henderson A, Smith C, Langley S, Laing R. (2006) 'A blinded, randomized controlled trial of neo-adjuvant celecoxib in patients with early prostate cancer.'. AMER SOC CLINICAL ONCOLOGY JOURNAL OF CLINICAL ONCOLOGY, Atlanta, GA: 42nd Annual Meeting of the American-Society-of-Clinical-Oncology 24 (18), pp. 232S-232S.
  • Bucca G, Carruba G, Saetta A, Muti P, Castagnetta M, Smith CP. (2004) 'Gene expression profiling of human cancers'. NEW YORK ACAD SCIENCES SIGNAL TRANSDUCTION AND COMMUNICATION IN CANCER CELLS, Erice, ITALY: Conference on Signal Transduction and Communication in Cancer Cells 1028, pp. 28-37.
    doi: 10.1196/annals.1322.003