Dobbin, Paul - University of Essex - School of Biological Sciences

个人简介

2001 - present Lecturer in Biochemistry, Dept. of Biological Sciences, University of Essex 1993 - 2000 Senior Research Associate, School of Biological Sciences, UEA Norwich 1987 - 1992 Research Assistant, Dept. of Pharmacy, King's College London PhD (London) 1992 - Medicinal Chemistry. Thesis title "Chelators Suitable for the Nutritional Supply of Metals" BSc Hons (Leicester) 1986 - Chemistry

研究领域

In the late 1980's it was first demonstrated that the anaerobic growth of Shewanella and Geobacter species could be supported by using insoluble Fe(III) as a respiratory substrate. These findings attracted attention from bioenergeticists, who were curious to know how electrons were transferred from primary dehydrogenases to the cell exterior with the concomitant generation of a proton electrochemical gradient. Subsequent experiments have revealed that electron transport to Fe(III) in Shewanella is via a network of multiheme c-type cytochromes, located at the inner membrane, in the periplasmic compartment, and at the outer membrane (where the terminal reduction of Fe(III) to Fe(II) occurs). Workers in the nuclear power industry are also interested in Fe(III) respiring microorganisms due to their tendency to reduce other metal cations, including soluble U(VI) and Tc(VII), which are then precipitated as insoluble lower valence forms. We are currently investigating the structures and functions of Shewanella multiheme cytochromes by a variety of techniques, including: (1) X-ray crystallography, which has yielded the molecular structure of an iron-induced flavocytochrome c3 (Ifc3); (2) magneto-optical spectroscopies (UV-VIS, EPR, MCD), which have shown the cytochromes to normally feature low-spin bis-His ligated c-hemes; (3) electochemistry, which has demonstrated different routes of electron passage into Ifc3, and has the potential for monitoring reconstitution of the electron transport chain to Fe(III) in vitro; and (4) protein engineering, which will enable identification of amino acid residues that are crucial to the cytochromes' involvement in Fe(III) respiration. We have noted a number of cytochromes in Shewanella to be specifically synthesised during growth with Fe(III), including the aforementioned Ifc3. Recent experiments have identified a transcription factor of the LysR family to positively regulate Ifc3 expression, and we are currently studying in more detail the molecular basis for Fe(III) responsive gene transcription in the bacterium. The importance of Fe(III) respiration has been recognized by the United States Department of Energy (DOE), who are funding the sequencing of the Shewanella putrefaciens MR-1 and Geobacter sufurreducens genomes. Exploitation of pre-published data generated in these programs is enabling us to identify the range of redox proteins involved in the anaerobic respiration of Fe(III) and other substrates by the use of 2D gel electrophoresis, microarray gene hybridization, and chromosomal mutations. Geobacter species also have potential applications in the field of bioremediation, which arise from their ability to couple the reduction of Fe(III) with the complete oxidation (to carbon dioxide) of petroleum components such as benzene and toluene under the anoxic conditions normally prevalent in polluted sites. We are currently seeking to identify and characterize the novel proteins involved in the anaerobic degradation of aromatic hydrocarbons by Geobacter using the genomic and proteomic techniques mentioned above. Finally, we are attempting to isolate novel Fe(III) respiring bacteria from microbial communities present in a number of different habitats. These include the human colonic microflora, where the reduction of Fe(III) to Fe(II) might lead to the onset of inflammatory disease states in the large intestine. Our studies on bacterial Fe(III) respiration in the Department of Biological Sciences at Essex are aided by external collaborations with: Workers in the Centre for Metalloprotein Spectroscopy and Biology, University of East Anglia, Norwich, which is jointly directed by Dr David Richardson and Prof Andrew Thomson, FRS; Prof Graeme Reid and co-workers in the Institute of Cell and Molecular Biology, University of Edinburgh

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Sinan Battah, Sherina Balaratnam, Adriana Casas, Sophie O’Neill, Christine Edwards, Alcira Batlle, Paul Dobbin and Alexander J MacRobert Macromolecular delivery of ALA for photodynamic therapy using dendrimer conjugates. Molecular Cancer Therapeutics, 2007, vol 6, pp 876-885 Gabriela M. Di Venosa, Adriana G. Casas, Sinan Battah, Paul Dobbin, Haydée Fukuda, Alexander J. MacRobert and Alcira Batlle (2006) Investigation of a novel dendritic derivative of 5-aminolaevulinic acid for photodynamic therapy, International Journal of Biochemistry & Cell Biology, Vol. 38, Issue 1, Pages 82-91 . Sinan Battah, Sophie O’Neill, Christine Edwards, Sherina Balaratnam, Paul Dobbin and Alexander J. MacRobert (2006) Enhanced porphyrin accumulation using dendritic derivatives of 5-aminolaevulinic acid for photodynamic therapy: An in vitro study, International Journal of Biochemistry & Cell Biology, Vol. 38, Issue 8, Pages 1382-1392. Lorena Rodriguez, Alcira Batlle, Gabriela Di Venosa, Sinan Battah, Paul Dobbin, Alexander J MacRobert and Adriana Casas (2006) Mechanisms of 5-aminolevulic acid ester uptake in mammalian cells, British Journal of Pharmacology, Vol. 147, Issue 7, Pages 825-833 SJ Field, PS Dobbin, MR Cheesman, NJ Watmough, AJ Thomson & DJ Richardson. Purification and magneto-optical spectroscopic characterization of cytoplasmic membrane and outer membrane multiheme c-type cytochromes from Shewanella frigidimarina NCIMB400. Journal of Biological Chemistry 275, 8515-8522 (2000) JN Butt, J Thornton, DJ Richardson & PS Dobbin. Voltammetry of a flavocytochrome c3: the lowest potential heme modulates fumarate reduction rates. Biophysical Journal 78, 1001-1009 (2000) V Bamford, PS Dobbin, DJ Richardson & AM Hemmings. Open conformation of a flavocytochrome c3 fumarate reductase. Nature Structural Biology 6, 1104-1107 (1999) PS Dobbin, JN Butt, AK Powell, GA Reid & DJ Richardson. Characterization of a flavocytochrome that is induced during the anaerobic respiration of Fe(III) by Shewanella frigidimarina NCIMB400. Biochemical Journal 342, 439-448 (1999) PS Dobbin, JP Carter, C Garcia-Salamanca San Juan, M von Hobe, AK Powell & DJ Richardson. Dissimilatory Fe(III) reduction by Clostridium beijerinckii isolated from freshwater sediment using Fe(III) maltol enrichment. FEMS Microbiology Letters 176, 131-138 (1999) V Bamford, PS Dobbin, S Lee, A Reilly, AK Powell, DJ Richardson & AM Hemmings. Crystallization and preliminary X-ray crystallographic analysis of a periplasmic tetraheme flavocytochrome c3 from Shewanella frigidimarina NCIMB400 which has fumarate reductase activity. Acta Crystallographica Section D 55, 1222-1225 (1999)