Yr Athro Colin Berry

Reader

Ysgol y Biowyddorau

Email:: berry@cardiff.ac.uk
Telephone:: +44 (0)29 2087 4508
Fax:: +44 (0)29 2087 4305
Location:: Cardiff School of Biosciences, Main Building, Park Place, Cardiff, CF10 3AT , Adeilad Syr Martin Evans, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX

: Sylwebydd y cyfryngau
: Ar gael fel goruchwyliwr ôl-raddedig

Research Overview

Work in Dr Berry’s laboratory is centred around two strategies for the control of tropical disease:

• Studies of insecticidal bacteria that can be used in the biological control of vector insects;

• Investigations of potential new drug targets in the parasites

Research Division

Organisms and Environment

BSc (Hons) Biochemistry, University of Southampton, 1984.
PhD Biochemistry, University of Bristol, 1988.
Postdoctoral Research Fellow, Institute of Molecular and Cell Biology, National University of Singapore, 1988-1992.
E. Alan Johnston Royal Society Research Fellow, Cardiff School of Biosciences, Cardiff University, 1992-2002.
Lecturer in Biochemistry, Cardiff School of Biosciences, Cardiff University, 2000-2003.
Senior Lecturer in Biochemistry, Cardiff School of Biosciences, Cardiff University, 2003-2009.
Visiting Professor, Agronomy and Veterinary Faculty, University of Brasilia, Brazil, 2008-Present.
DSc, University of Bristol, 2008.
Reader, Cardiff School of Biosciences, Cardiff University, 2009-Present.

2013

Vidal Quist, J.et al. 2013. 'Bacillus thuringiensis' colonises plant roots in a phylogeny-dependent manner. FEMS Microbiology Ecology 86(3), pp. 474-489. (10.1111/1574-6941.12175)
Pereira, E.et al. 2013. Comparative toxicity of 'Bacillus thuringiensis' Berliner Strains to larvae of simuliidae (Insecta: Diptera). Bt Research 4(2), pp. 8-13.
Berry, C. 2013. Metrics-based assessments of research: Incentives for 'institutional plagiarism'?. Science and Engineering Ethics 19(2), pp. 337-340. (10.1007/s11948-012-9352-0)
Berry, C. and Goldberg, D. E. 2013. Histo-Aspartic Proteinase. In: Rawlings, N. D. and Salvesen, G. eds. Handbook of Proteolytic Enzymes (Third Edition)., Vol. 1. Elsevier Academic Press, pp. 105-108., (10.1016/B978-0-12-382219-2.00019-3)
Berry, C. and Goldberg, D. E. 2013. Food vacuole plasmepsins. In: Rawlings, N. D. and Salvesen, G. eds. Handbook of Proteolytic Enzymes (Third Edition)., Vol. 1. Elsevier Academic Press, pp. 98-103., (10.1016/B978-0-12-382219-2.00017-X)
Berry, C. 2013. Ddi1 and related proteins. In: Rawlings, N. D. and Salvesen, G. eds. Handbook of Proteolytic Enzymes (Third Edition)., Vol. 1. Elsevier Academic Press, pp. 255-258., (10.1016/B978-0-12-382219-2.00061-2)

2012

Dehio, C., Berry, C. and Bartenschlager, R. 2012. Persistent intracellular pathogens. FEMS Microbiology Reviews 36(3), pp. 513-513. (10.1111/j.1574-6976.2012.00336.x)
Berry, C. 2012. The bacterium, Lysinibacillus sphaericus, as an insect pathogen. Journal of Invertebrate Pathology 109(1), pp. 1-10. (10.1016/j.jip.2011.11.008)
Kuadkitkan, A., Smith, D. R. and Berry, C. 2012. Investigation of the Cry4B–Prohibitin interaction in Aedes aegypti cells. Current Microbiology 65(4), pp. 446-454. (10.1007/s00284-012-0178-4)
Monnerat, R.et al. 2012. Activity of a Brazilian strain of Bacillus thuringiensis israelensis against the cotton boll weevil Anthonomus grandis Boheman (Coleoptera: Tenebrionidae). Neotropical Entomology 41(1), pp. 62-67. (10.1007/s13744-011-0008-6)

2011

McKay, P.et al. 2011. Identification of plasmepsin inhibitors as selective anti-malarial agents using ligand based drug design. Bioorganic & Medicinal Chemistry Letters 21(11), pp. 3335-3341. (10.1016/j.bmcl.2011.04.015)
White, R. E., Powell, D. J. and Berry, C. 2011. HIV proteinase inhibitors target the Ddi1-like protein of Leishmania parasites. The FASEB Journal 25(5), pp. 1729-1736. (10.1096/fj.10-178947)
Opota, O.et al. 2011. Bacillus sphaericus binary toxin elicits host cell autophagy as a response to intoxication. PLoS ONE 6(2), article number: e14682. (10.1371/journal.pone.0014682)
White, R. E.et al. 2011. The retroviral proteinase active site and the N-terminus of Ddi1 are required for repression of protein secretion. FEBS Letters 585(1), pp. 139-142. (10.1016/j.febslet.2010.11.026)
Guerra, Y.et al. 2011. Predicting functional residues of the Solanum lycopersicum aspartic protease inhibitor (SLAPI) by combining sequence and structural analysis with molecular docking. Journal of Molecular Modeling 18(6), pp. 2673-2687. (10.1007/s00894-011-1290-2)

2010

Berry, C. and Silva-Filha, M. H. N. L. 2010. Bacillus sphaericus taxonomy and genetics. In: Gilbert, L. I. and Gill, S. S. eds. Insect Control.. Elsevier, pp. 308-312.
Berry, C. and Baker, M. D. 2010. Inside protein structures: teaching in three dimensions. Biochemistry and Molecular Biology Education 38(6), pp. 425-429. (10.1002/bmb.20434)
Monnerat, R. G.et al. 2010. Selection of Bacillus thuringiensis strains toxic against cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae). BioAssay 5 (10.14295/BA.v5.0.70)

2009

Abdoarrahem, M. M.et al. 2009. A genetic basis for the alkaline-activation of germination in Bacillus thuringiensis subsp. israelensis. Applied and Environmental Microbiology 75(19), pp. 6410-6413. (10.1128/AEM.00962-09)
Monnerat, R. G.et al. 2009. Translocation and insecticidal activity of Bacillus thuringiensis living inside of plants. Microbial Biotechnology 2(4), pp. 512-520. (10.1111/j.1751-7915.2009.00116.x)
Kandil, S.et al. 2009. Discovery of a novel HCV helicase inhibitor by a de novo drug design approach. Bioorganic & Medicinal Chemistry Letters 19(11), pp. 2935-2937. (10.1016/j.bmcl.2009.04.074)
Padron-Garcia, J. A.et al. 2009. Quantitative Structure Activity Relationship of IA3-like peptides as aspartic proteinase inhibitors. Proteins: Structure, Function and Bioinformatics 75(4), pp. 859-869. (10.1002/prot.22295)
De Melo, J. V.et al. 2009. Cry48Aa/Cry49Aa binary toxin from Bacillus sphaericus displays cytopathological effects on susceptible and binary toxin-resistant Culex quinquefasciatus larvae. Applied and Environmental Microbiology 75(14), pp. 4782-4789. (10.1128/AEM.00811-09)
Ramirez, A. R.et al. 2009. Generation of an affinity matrix useful in the purification of inhibitors of plasmepsin II, an antimalarial drug target. Biotechnology and Applied Biochemistry 52(2), pp. 149-157. (10.1042/BA20080015)
Santos, K.et al. 2009. Selection and characterization of the Bacillus thuringiensis strains toxic to Spodoptera eridania (Cramer), Spodoptera cosmiodes (Walker) and Spodoptera frugiperda (Smith) (Lepidoptera:Noctuidae). Biological Control 50(2), pp. 157-163. (10.1016/j.biocontrol.2009.03.014)

2008

Jones, G. W.et al. 2008. The Cry-48Aa-Cry49Aa binary toxin from Bacillus sphaericus exhibits highly-restricted target specificity. Environmental Microbiology 10(9), pp. 2418-2424. (10.1111/j.1462-2920.2008.01667.x)
Guerra, Y.et al. 2008. Natural inhibitor of plasmepsin II from the gorgonian Plexaura homomalla: partial purification and characterization [Abstract]. FEBS Journal 275(S1), pp. 450. (10.1111/j.1742-4658.2008.06448.x)
Brancale, A.et al. 2008. Discovery of a novel HCV helicase inhibitor by a de novo drug design approach. Antiviral Research 78(2), pp. A22. (10.1016/j.antiviral.2008.01.030)
Mokarzel-Falcon, L.et al. 2008. In silico study of the human rhodopsin and meta rhodopsin II/S-arrestin complexes: Impact of single point mutations related to retina degenerative diseases. Proteins: Structure, Function and Genetics 70(4), pp. 1133-1141. (10.1002/prot.21873)
Hu, X.et al. 2008. Complete genome sequences of the mosquitocidal bacterium Bacillus sphaericus C3-41 and comparisons with closely related Bacillus species. Journal of Bacteriology 190(8), pp. 2892-2902. (10.1128/JB.01652-07)
Berry, C. 2008. Bacillus sphaericus. In: Capinera, J. ed. Encyclopaedia of Entomology., Vol. 1. London: Springer, pp. 345-348.

2007

Jones, G. W.et al. 2007. A new Cry toxin with a unique two-component dependency from Bacillus sphaericus. The FASEB Journal (10.1096/fj.07-8913com)
Winterburn, T. J.et al. 2007. N-terminal extension of the yeast IA3 aspartic proteinase inhibitor relaxes the strict intrinsic selectivity. FEBS journal 274(14), pp. 3685-3694. (10.1111/j.1742-4658.2007.05901.x)
Wu, E.et al. 2007. Characterization of a cryptic plasmid from Bacillus sphaericus strain LP1-G. Plasmid 57(3), pp. 296-305. (10.1016/j.plasmid.2006.11.003)
Wirth, M. C.et al. 2007. Mtx toxins synergize bacillus sphaericus and cry11Aa against susceptible and insecticide-resistant culex quinquefasciatus larvae. Applied and Environmental Microbiology 73(19), pp. 6066-6071. (10.1128/AEM.00654-07)
Shea, M.et al. 2007. A family of aspartic proteases and a novel, dynamic and cell-cycle-dependent protease localization in the secretory pathway of toxoplasma gondii. Traffic 8(8), pp. 1018-1034. (10.1111/j.1600-0854.2007.00589.x)
Monnerat, R. G.et al. 2007. Screening of Brazilian Bacillus thuringiensis isolates active against Spodoptera frugiperda, Plutella xylostella and Anticarsia gemmatalis. Biological Control 41(3), pp. 291-295. (10.1016/j.biocontrol.2006.11.008)
Yang, Y.et al. 2007. Proteolytic stability of insecticidal toxins expressed in recombinant bacilli. Applied and Environmental Microbiology 73(1), pp. 218-225. (10.1128/AEM.01100-06)
Martins, ?. S.et al. 2007. Characterization of Bacillus thuringiensis isolates toxic to cotton boll weevil (Anthonomus grandis). Biological Control 40(1), pp. 65-68. (10.1016/j.biocontrol.2006.09.009)

2006

Stein, C.et al. 2006. Transcriptional analysis of the toxin-coding plasmid pBtoxis from bacillus thuringiensis subsp. israelensis. Applied and Environmental Microbiology 72(3), pp. 1771-1776. (10.1128/AEM.72.3.1771-1776.2006)
Gammon, K.et al. 2006. Conjugal transfer of a toxin-coding megaplasmid from Bacillus thuringiensis subsp. israelensis to mosquitocidal strains of Bacillus sphaericus. Applied and Environmental Microbiology 72(3), pp. 1766-1770. (10.1128/AEM.72.3.1766-1770.2006)
Winterburn, T. J.et al. 2006. Key features determining the specificity of aspartic proteinase inhibition by the helix-forming IA3 polypeptide. Journal of biological chemistry 282(9), pp. 6508-6516. (10.1074/jbc.M610503200)
Andrews, K. T.et al. 2006. Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria. Antimicrobial Agents and Chemotherapy 50(2), pp. 639-648. (10.1128/AAC.50.2.639-648.2006)
Manasherob, R.et al. 2006. Cyt1Ca from Bacillus thuringiensis subsp. israelensis: production in Escherichia coli and comparison of its biological activities with those of other Cyt-like proteins. Microbiology 152(9), pp. 2651-2659. (10.1099/mic.0.28981-0)
Winterburn, T. J.et al. 2006. Adaptation of the behaviour of an aspartic proteinase inhibitor by relocation of a lysine residue by one helical turn. Biological Chemistry 387(8), pp. 1139-1142. (10.1515/BC.2006.140)
Martins, T. M.et al. 2006. The activity and inhibition of the food vacuole plasmepsin from the rodent malaria parasite Plasmodium chabaudi. Acta Tropica 97(2), pp. 212-218. (10.1016/j.actatropica.2005.11.001)

2005

Whittingham, J. L.et al. 2005. dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors. Structure 13(2), pp. 329-338. (10.1016/j.str.2004.11.015)
Wyatt, D. M. and Berry, C. 2005. Antimalarial effects of HIV proteinase inhibitors: common compounds but structurally distinct enzymes. International Journal of Infectious Diseases 192(4), pp. 705-706. (10.1086/432079)
Jones, S. M.et al. 2005. Analogues of thiolactomycin as potential antimalarial agents. Journal of Medicinal Chemistry 48(19), pp. 5932-5941. (10.1021/jm049067d)
Monnerat, R. G.et al. 2005. Screening of Bacillus thuringiensis strains effective against mosquitoes. Pesquisa Agropecuária Brasileira 40(2) (10.1590/S0100-204X2005000200001)

2004

Jones, S. M.et al. 2004. Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents. Bioorganic & Medicinal Chemistry 12(4), pp. 683-692. (10.1016/j.bmc.2003.11.023)
Gul, S.et al. 2004. Staphylococcus aureus DNA ligase: characterization of its kinetics of catalysis and development of a high-throughput screening compatible chemiluminescent hybridization protection assay. Biochemical Journal 383(3), pp. 551-559. (10.1042/BJ20040054)
Monnerat, R.et al. 2004. Screening of Brazilian Bacillus sphaericus strains for high toxicity against Culex quinquefasciatus and Aedes aegypti. Journal of Applied Entomology 128(7), pp. 469-473. (10.1111/j.1439-0418.2004.00874.x)
Berry, C. 2004. Bacillus Sphaericus. In: Encyclopedia of Entomology.. Springer, pp. 224., (10.1007/0-306-48380-7_389)
Berry, C. and Goldberg, D. E. 2004. Plasmepsin II. In: Barrett, A. J., Woessner, J. F. and Rawlings, N. D. eds. Handbook of Proteolytic Enzymes, 2nd ed., Vol. 1. Aspartic and Metallo Peptidases Amsterdam: Elsevier Academic Press, pp. 73-75., (10.1016/B978-0-12-079611-3.50023-9)
Berry, C. and Goldberg, D. E. 2004. Plasmepsins. In: Barrett, A. J., Woessner, J. F. and Rawlings, N. D. eds. Handbook of Proteolytic Enzymes (Second Edition) Volume 1: Aspartic and Metallo Peptidases.. Elsevier, pp. 70-73., (10.1016/B978-0-12-079611-3.50022-7)

2003

de Maagd, R. A.et al. 2003. Structure, diversity, and evolution of protein toxins from spore-forming entomopathogenic bacteria. Annual Review of Genetics 37(1), pp. 409-433. (10.1146/annurev.genet.37.110801.143042)
Dell'Agli, M.et al. 2003. In vitro studies on the mechanism of action of two compounds with antiplasmodial activity: ellagic acid and 3,4,5-Trimethoxyphenyl(6?-O-Galloyl)-β-D-glucopyranoside. Planta Medica 69(2), pp. 162-164. (10.1055/s-2003-37706)
Parkhill, J. and Berry, C. 2003. Genomics: Relative pathogenic values. Nature 423(6935), pp. 23-25. (10.1038/423023a)

2002

Berry, C.et al. 2002. Complete sequence and organization of pBtoxis, the toxin-coding plasmid of Bacillus thuringiensis subsp. israelensis. Applied and Environmental Microbiology 68(10), pp. 5082-5095. (10.1128/AEM.68.10.5082-5095.2002)
Partridge, M. R. and Berry, C. 2002. Insecticidal activity of the Bacillus sphaericus Mtx1 toxin against Chironomus riparus. Journal of Invertebrate Pathology 79(2), pp. 135-136. (10.1016/S0022-2011(02)00025-3)
Williamson, A. L.et al. 2002. Cleavage of hemoglobin by hookworm cathepsin D aspartic proteases and its potential contribution to host specificity. The FASEB Journal 16(11), pp. 1458-1460. (10.1096/fj.02-0181fje)
Wyatt, D. M. and Berry, C. 2002. Activity and inhibition of plasmepsin IV, a new aspartic proteinase from the malaria parasite, Plasmodium falciparum. FEBS Letters 513(2-3), pp. 159-162. (10.1016/S0014-5793(02)02241-X)

2001

Kasper, G.et al. 2001. A calreticulin-like molecule from the human hookworm Necator americanus interacts with C1q and the cytoplasmic signalling domains of some integrins. The Journal of Immunology 23(3), pp. 141-152. (10.1046/j.1365-3024.2001.00366.x)
Schwartz, J.et al. 2001. Permeabilization of model lipid membranes by Bacillus sphaericus mosquitocidal binary toxin and its individual components. Journal of Membrane Biology 184(2), pp. 171-183. (10.1007/s00232-001-0086-1)
Coombs, G. H.et al. 2001. Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets. Trends in Parasitology 17(11), pp. 532-537. (10.1016/S1471-4922(01)02037-2)

2000

Girdwood, K. and Berry, C. 2000. The disulphide bond arrangement in the major pepsin inhibitor PI-3 of Ascaris suum. FEBS Letters 474(2-3), pp. 253-255. (10.1016/S0014-5793(00)01589-1)
Delécluse, A., Juárez-Pérez, V. and Berry, C. 2000. Vector-active toxins: structure and diversity. In: Charles, J., Delécluse, A. and Nielsen-Le Roux, C. eds. Entomopathogenic Bacteria: from Laboratory to Field Application.. Springer, pp. 101-125., (10.1007/978-94-017-1429-7_6)

1999

Berry, C.et al. 1999. A distinct member of the aspartic proteinase gene family from the human malaria parasite Plasmodium falciparum. FEBS Letters 447(2-3), pp. 149-154. (10.1016/S0014-5793(99)00276-8)
Tyas, L.et al. 1999. Naturally-occurring and recombinant forms of the aspartic proteinases plasmepsins I and II from the human malaria parasite Plasmodium falciparum. FEBS Letters 454(3), pp. 210-214. (10.1016/S0014-5793(99)00805-4)
Pritchard, D. I.et al. 1999. A hookworm allergen which strongly resembles calreticulin. Parasite Immunology 21(9), pp. 439-450. (10.1046/j.1365-3024.1999.00238.x)
Humphreys, M. J.et al. 1999. The aspartic proteinase from the rodent parasite Plasmodium berghei as a potential model for plasmepsins from the human malaria parasite, Plasmodium falciparum. FEBS Letters 463(1-2), pp. 43-48. (10.1016/S0014-5793(99)01597-5)
Berry, C. 1999. Proteases as drug targets for the treatment of malaria. In: Dunn, B. M. ed. Proteases of Infectious Agents.. San Diego, CA: Academic Press, pp. 165-188., (10.1016/B9-78-012420-5/10950-0338)

1998

Humphreys, M. J. and Berry, C. 1998. Variants of theBacillus sphaericusBinary Toxins: implications for differential toxicity of strains. Journal of Invertebrate Pathology 71(2), pp. 184-185. (10.1006/jipa.1997.4711)
Moon, R. P.et al. 1998. Studies on Plasmepsins I and II from the Malarial Parasite Plasmodium falciparum and their exploitation as drug targets. Advances in Experimental Medicine and Biology 436, pp. 397-406. (10.1007/978-1-4615-5373-1_56)
Tyas, L.et al. 1998. Plasmepsins I and II from the malarial parasite Plasmodium falciparum. Presented at: 7th International Conference on Aspartic Proteinases, Banff, Canada, 22-27 October 1996 Presented at James, M. N. G. ed.Aspartic Proteinases: Retroviral and Cellular Enzymes, Vol. 436. Advances in Experimental Medicine and Biology New York, NY: Springer pp. 407-411., (10.1007/978-1-4615-5373-1_57)

1997

Charles, J.et al. 1997. Binding of the 51- and 42-kDa individual components from the Bacillus sphaericus crystal toxin to mosquito larval midgut membranes from Culex and Anopheles sp. (Diptera: Culicidae). FEMS Microbiology Letters 156(1), pp. 153-159. (10.1111/j.1574-6968.1997.tb12721.x)
Berry, C. 1997. New targets for antimalarial therapy: the plasmepsins, malaria parasite aspartic proteinases. Biochemical Education 25(4), pp. 191-194. (10.1016/S0307-4412(97)00130-1)
Moon, R. P.et al. 1997. Expression and characterisation of Plasmepsin I from Plasmodium falciparum. European Journal of Biochemistry 244(2), pp. 552-560. (10.1111/j.1432-1033.1997.00552.x)

1996

Kay, J.et al. 1996. Aspartic Proteinases from parasites. In: Advances in Experimental Medicine and Biology., Vol. 389. Springer, pp. 247-250., (10.1007/978-1-4613-0335-0_31)

1995

Berry, C.et al. 1995. Aspartic proteinases from the human malaria parasite Plasmodium Falciparum. Presented at: 5th International Conference on Aspartic Proteinases, Kawashima cho, Japan, 19-24 September 1993 Presented at Takahashi, K. ed.Aspartic Proteinases: Structure, Function, Biology, and Biomedical Implications, Vol. 362. Advances in Experimental Medicine and Biology New York, NY: Springer pp. 511-518., (10.1007/978-1-4615-1871-6_67)

1994

Dame, J. B.et al. 1994. Sequence, expression and modeled structure of an aspartic proteinase from the human malaria parasite Plasmodium falciparum. Molecular and Biochemical Parasitology 64(2), pp. 177-190. (10.1016/0166-6851(94)90024-8)
Hill, J.et al. 1994. High level expression and characterisation of Plasmepsin II, an aspartic proteinase from Plasmodium falciparum. FEBS Letters 352(2), pp. 155-158. (10.1016/0014-5793(94)00940-6)

1992

Oei, C., Hindley, J. and Berry, C. 1992. Binding of purified Bacillus sphaericus binary toxin and its deletion derivatives to Culex quinquefasciatus gut: elucidation of functional binding domains. Journal of General Microbiology 138(7), pp. 1515-1526. (10.1099/00221287-138-7-1515)

1991

Berry, C., John, H. and Coreen, O. 1991. The bacillus sphaericus toxins and their potential for biotechnological development. In: Biotechnology for Biological Control of Pests and Vectors.. CRC Press, pp. 35-52.

1990

Oei, C., Hindley, J. and Berry, C. 1990. An analysis of the genes encoding the 51.4- and 41.9-kDa toxins of Bacillus sphaericus2297 by deletion mutagenesis: the construction of fusion proteins. FEMS Microbiology Letters 72(3), pp. 265-273. (10.1111/j.1574-6968.1990.tb03900.x)
Davidson, E. W.et al. 1990. Interaction of the Bacillus sphaericusmosquito larvicidal proteins. Canadian Journal of Microbiology 36(12), pp. 870-878. (10.1139/m90-151)

1989

Berry, C.et al. 1989. Nucleotide sequence of two toxin gen fromBacillus sphaericus1AB59: sequence comparisons between five highly toxinogenic strains. Nucleic Acids Research 17(18), pp. 7516. (10.1093/nar/17.18.7516)

1988

Hindley, J. and Berry, C. 1988. Bacillus sphaericusstrain 2297: nucleotide sequence of 41.9 kDa toxin gene. Nucleic Acids Research 16(9), pp. 4168. (10.1093/nar/16.9.4168)

1987

Hindley, J. and Berry, C. 1987. Identification, cloning and sequence analysis of the Bacillus sphaericus 1593 41.9 kD larvicidal toxin gene. Molecular Microbiology 1(2), pp. 187-194. (10.1111/j.1365-2958.1987.tb00511.x)
Berry, C. and Hindley, J. 1987. Bacillus sphaericusstrain 2362: identification and nucleotide sequence of the 41.9kDa toxin gene. Nucleic Acids Research 15(14), pp. 5891. (10.1093/nar/15.14.5891)

The Insecticidal Toxins of Bacillus sphaericus and Bacillus thuringiensis

Some strains of the bacterium Bacillus sphaericus produce a variety of toxins that act specifically against mosquito larvae with few effects on non-target organisms and no harmful effects on humans. This makes it a useful agent for the biological control of mosquito populations which may constitute major pests and vectors of a range of extremely serious human diseases (including malaria, elephantiasis, yellow fever and dengue fever). Research in Dr Berry's group includes investigations of toxin mode of action, new toxin discovery, regulation of toxin gene expression and strain improvement for enhanced biological control. A recent collaboration has resulted in the complete sequencing of a Bacillus sphaericus genome and this will enhance our understanding of this biological control agent.

In order to study the genetics of the insecticidal toxins of Bacillus thuringiensis israelensis, a collaboration with the Sanger Centre was also established, which led to the elucidation of the complete sequence of the entire virulence megaplasmid (approx. 128kb) that encodes all known toxins (and helper proteins) in this bacterium. Further studies on the influence of this plasmid on its host bacterium are underway.

Parasite Aspartic Proteinases

Aspartic proteinases perform critical functions in many parasites that cause serious human or livestock diseases and are thus excellent targets for the design of novel anti-parasitic drugs. Such functions include roles in invasion of the host or as part of the parasite's digestive system. Dr Berry's group is studying these enzymes from a range of protozoan and helminthic parasites as targets for inhibitor design. The malaria parasite Plasmodium falciparum may produce up to ten aspartic proteinases (the plasmepsins). Some of these plasmepsins are involved in parasite digestion of host red cell haemoglobin and inhibition of these enzymes can lead to parasite death. Dr Berry's group has cloned and expressed plasmepsins I and II in recombinant form and has completed their full kinetic characterisation with a series of synthetic substrates and a number of inhibitors. With industrial collaborators, a compound which kills parasites in red blood cells in culture and shows selective inhibition of plasmepsin I has been identified. The results of these studies will facilitate the design of new inhibitory compounds as potential anti-malarial drugs.

Grant Funding

Dr Berry's work has received funding from a variety of sources including The Royal Society, the UK research councils, the Welsh Development Agency, the World Health Organisation, the Leverhulme Trust, the Wellcome Trust, the British Council, the Welsh Assembly Government, the Cardiff Partnership Fund & various industrial sponsors.

Current Collaborators

Prof Esther Alonso Becerra and Alexander Padrón, Faculty of Chemistry, University of Havana
Dr Daniel Bur, Actelion Ltd, Switzerland
Prof Maya Chávez, Centro de Estudio de Proteínas, University of Havana, Cuba
Dr Ana Domingos, Instituto Nacional de Engenharia e Tecnologia Industrial, Lisbon, Portugal
Prof Brian Federici and Dr Margaret Wirth, University of California, Riverside, USA
Dr James McCarthy, Queensland Institute of Medical Research, Brisbane, Australia
Dr Rose Monnerat, EMBRAPA, Brasilia, Brazil
Dr Christina Nielsen-LeRoux, Institut Pasteur, Paris, France
Dr David Powell, GlaxoSmithKline, Harlow, UK
Dr Maria Helena N.L. Silva-Filha, Centro de Pesquisas Aggeu Magalhães-FIOCRUZ, Recife, Brazil
Dr Marcelo Soares, Bthek Biotechnologia, Brasilia, Brazil
Dr Zhiming Yuan, Wuhan Institute of Virology, Wuhan, China
Prof Arieh Zaritsky, Ben Gurion University of the Negev, Israel