Professor David Hornby

School of Biosciences

Professor of Biochemistry

d.hornby@sheffield.ac.uk
+44 114 222 4232
Firth Court

Full contact details

Professor David Hornby
School of Biosciences
Firth Court
Western Bank
Sheffield
S10 2TN
Profile

I started my research career interested in metabolic enzyme structure and function and along the way I have turned my attention to increasingly more complex enzymes and proteins, especially those involved in nucleic acid transactions.

This has led me to question the foundations of our understanding of enzyme catalysis.

My research currently involves a series of collaborations aimed at exploring the evolution of enzyme mechanism via random mutagenesis of several enzymes and proteins.

A more recent interest has arisen through collaboration with the Microbiology community at Sheffield and is the challenge of understanding the molecular basis of antibiotic resistance, in particular methicillin resistance.

Career history

  • 2013 - 2015: Director of Innovation, Liverpool Life Sciences UTC
  • 2012: Professor of Biochemistry Department of Molecular Biology and Biotechnology (on sabbatical leave at the Liverpool School of Tropical Medicine)
  • 2007 - 2012: Head of the Department of Molecular Biology and Biotechnology
  • 2008 - 2011: Director of Enterprise in Life Sciences
  • 1999 - 2007: Professor of Biochemistry Department of Molecular Biology and Biotechnology
  • 1999 - 2002: Director of the Transgenomic Research Laboratory
  • 1998 - 1999: Reader Department of Molecular Biology and Biotechnology
  • 1994 - 1998: Senior Lecturer Department of Molecular Biology and Biotechnology
  • 1992 - 1993: Visiting Scientist Department Molecular Biology The Scripps Research Institute California
  • 1990 - 1994: Lecturer Department of Molecular Biology and Biotechnology
  • 1990: EMBO fellowship Gene Expression Program EMBL, Heidelberg
  • 1986 - 1990: Lecturer Department of Biochemistry
  • 1985 - 1986: Postdoctoral research associate Biozentrum der Universitat Basel, Switzerland
  • 1984 - 1985: Postdoctoral research associate Departments of Biochemistry, Sheffield and Genetics, Leeds
  • 1980 - 1984: PhD (Biochemistry) University of Sheffield
Research interests

DNA Modifying Enzymes: Cytosine-C5-specific DNA methyltransferases, in particular the monospecific enzyme, M.HhaI and the multi-specific enzyme M.SPRI. The aim is to identify essential residues involved in base flipping in the former and to determine the structural basis of multiple specificity in the latter.

RNA and DNA Polymerases present opportunities for developing a range of molecular biology methods and are in themselves key enzymes in cellular physiology. The former are of interest as targets for structure determination by new cryo-EM methods and the latter is a work horse for the development of in vitro mutagenesis methods in use in my lab.

Multi-enzyme complexes often contain components that are shared by other complexes. Using random mutagenesis methods, we are interested in the evolutionary pressures facing such promiscuous subunits, such as the E3 component of bacterial oxoacid dehydrogenases.

Enzymes are thought to bring substrates into precise alignment in order to stimulate product formation. Since many naturally occurring enzymes that catalyze the same reaction exhibit significant primary structural diversity, we are using random mutagenesis combined with screening and structural methods, to identify the sensitive and essential elements of primary structure in a range of enzyme catalyzed reactions and antibiotic resistance targets.

Publications

Show: Featured publications All publications

Journal articles

  • Waghmare SP, Pousinis P, Hornby DP & Dickman MJ (2009) . J Chromatogr A, 1216(9), 1377-1382.
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All publications

Books

  • Gjerde DT, Hoang L & Hornby D (2009) . Wiley.
  • Gjerde DT, Hanna CP & Hornby D (2002) . Wiley.
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Journal articles

  • Panchal VV, Griffiths C, Mosaei H, Bilyk B, Sutton JAF, Carnell OT, Hornby DP, Green J, Hobbs JK, Kelley WL , Zenkin N et al (2020) . PLoS Pathogens, 16(7).
  • Hornby D (2017) . The Biochemist, 39(6), 51-51.
  • Snijders AP, Hautbergue GM, Bloom A, Williamson JC, Minshull TC, Phillips HL, Mihaylov SR, Gjerde DT, Hornby DP, Wilson SA , Hurd PJ et al (2015) . RNA, 21(3), 347-359.
  • Qureshi MS, Sheikh QI, Hill R, Brown PE, Dickman MJ, Tzokov SB, Rice DW, Gjerde DT & Hornby DP (2013) . Anal Biochem, 439(1), 47-49.
  • Xu W, Liu L & Hornby D (2012) . Molecules, 17(10), 12086-12101.
  • Xu W, Liu L, Brown NJ, Christian S & Hornby D (2012) . Molecules, 17(1), 796-808.
  • Waghmare SP, Pousinis P, Hornby DP & Dickman MJ (2009) . J Chromatogr A, 1216(9), 1377-1382.
  • Dickman MJ & Hornby DP (2006) . RNA, 12(4), 691-696.
  • Hanna C, Gjerde D, Nguyen L, Dickman M, Brown P & Hornby D (2006) . ANAL BIOCHEM, 350(1), 128-137.
  • Dickman MJ, Sedelnikova SE, Rafferty JB & Hornby DP (2004) . J Biochem Biophys Methods, 58(1), 39-48.
  • Brown PE, Hornby DP & Dickman MJ (2004) Identification of nuclear protein complexes using open tube capillary chromatography. AIChE Annual Meeting, Conference Proceedings, 1917.
  • Harris VH, Smith CL, Cummins WJ, Hamilton AL, Hornby DP & Williams DM (2003) . Org Biomol Chem, 1(12), 2070-2074.
  • Roberts RJ, Belfort M, Bestor T, Bhagwat AS, Bickle TA, Bitinaite J, Blumenthal RM, Degtyarev SK, Dryden DTF, Dybvig K , Firman K et al (2003) . Nucleic Acids Res, 31(7), 1805-1812.
  • Harris VH, Smith CL, Jonathan Cummins W, Hamilton AL, Adams H, Dickman M, Hornby DP & Williams DM (2003) . J Mol Biol, 326(5), 1389-1401.
  • Pinarbasi H, Pinarbasi E & Hornby DP (2003) . J Bacteriol, 185(4), 1284-1288.
  • Dickman MJ, Ingleston SM, Sedelnikova SE, Rafferty JB, Lloyd RG, Grasby JA & Hornby DP (2002) . Eur J Biochem, 269(22), 5492-5501.
  • Bahrami AR, Dickman MJ, Matin MM, Ashby JR, Brown PE, Conroy MJ, Fowler GJS, Rose JP, Sheikh QI, Yeung AT & Hornby DP (2002) . Anal Biochem, 309(2), 248-252.
  • Matin MM, Baumer A & Hornby DP (2002) . Hum Mutat, 20(4), 305-311.
  • Zhou L, Cheng X, Connolly BA, Dickman MJ, Hurd PJ & Hornby DP (2002) . J Mol Biol, 321(4), 591-599.
  • Pinarbasi H, Pinarbasi E & Hornby D (2002) . J Biochem Mol Biol, 35(3), 348-351.
  • Matin MM, Andrews PW & Hornby DP (2002) . Anal Biochem, 304(1), 47-54.
  • Ingleston SM, Dickman MJ, Grasby JA, Hornby DP, Sharples GJ & Lloyd RG (2002) . Eur J Biochem, 269(5), 1525-1533.
  • Dickman MJ, Matin MM & Hornby DP (2002) . Anal Biochem, 301(2), 290-297.
  • Dickman MJ, Conroy MJ, Grasby JA & Hornby DP (2002) . RNA, 8(2), 247-251.
  • Harris VH, Smith C, Cummins J, Hamilton A, Hornby DP & Williams DM (2002) DNA replication with the mutagenic nucleotide dPTP; Effects of tautomerism on nucleotide incorporation. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 5, 215-220.
  • Yassaee VR, Zeinali S, Harirchi I, Jarvandi S, Mohagheghi MA, Hornby DP & Dalton A (2002) . Breast Cancer Res, 4(4), R6.
  • Daniels M, Dickman M & Hornby D (2001) Rapid analysis of biochemical modifications in DNA fragments - Visualisation of phosphorylation and cytosine deamination in single 15 minute analyses.. AM J HUM GENET, 69(4), 462-462.
  • Dickman M, Piff M, Daniels M & Hornby D (2001) Rapid, high precision analysis of DNA and RNA footprinting reactions utilising the WAVE (R) Nucleic Acid Fragment Analysis System.. AM J HUM GENET, 69(4), 468-468.
  • Yassaee VR, Zeinali S, Harirchi I, Mohagheghi MA, Hornby DP & Dalton A (2001) Novel mutations in the BRCA1 and BRCA2 gene in Iranian women with early-onset Breast Cancer. J MED GENET, 38, S54-S54.
  • Dickman M & Hornby DP (2001) Analysis of nucleic acid modification enzyme reactions using IP RP HPLC. J MED GENET, 38, S71-S71.
  • Lee SE, Sidorov A, Gourlain T, Mignet N, Thorpe SJ, Brazier JA, Dickman MJ, Hornby DP, Grasby JA & Williams DM (2001) . Nucleic Acids Res, 29(7), 1565-1573.
  • Ortega B, Beesley AH, Hornby D & White SJ (2000) . Biochem Biophys Res Commun, 277(1), 147-151.
  • Rösler A, Panayotou G, Hornby DP, Barlow T, Brown T, Pearl LH, Savva R & Blackburn GM (2000) . Nucleosides Nucleotides Nucleic Acids, 19(10-12), 1505-1516.
  • Dickman M & Hornby DP (2000) . Anal Biochem, 284(1), 164-167.
  • Matin MM & Hornby DP (2000) . Anal Biochem, 278(1), 46-51.
  • Thompson MJ, Mekhalfia A, Hornby DP & Blackburn GM (1999) Synthesis of two stable nitrogen analogues of S-adenosyl-L-methionine. J ORG CHEM, 64(20), 7467-7473.
  • Hornby D (1999) . Mycologist, 13(2), 96-IBC.
  • Hurd PJ, Whitmarsh AJ, Baldwin GS, Kelly SM, Waltho JP, Price NC, Connolly BA & Hornby DP (1999) . J Mol Biol, 286(2), 389-401.
  • Fox L, Dolman E, Hornby D, Lane P, O'Rourke A, Roberts C & Roscoe T (1999) . Journal of Medical Internet Research, 1(SUPPL. 1).
  • Harris VH, Hamilton A, Williams DM & Hornby DP (1999) Studying the function of methyltransferases using nucleotide analogue based random mutagenesis. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 2, 209-212.
  • Brewis IA, Clayton R, Browes CE, Martin M, Barratt CL, Hornby DP & Moore HD (1998) . Mol Hum Reprod, 4(12), 1136-1144.
  • Matin MM & Hornby DP (1998) . Biochem Soc Trans, 26(4), S394.
  • Beesley AH, Hornby D & White SJ (1998) Novel splicing of ROMK K+ channel RNA generates new isoforms in rat kidney. JOURNAL OF PHYSIOLOGY-LONDON, 511P, 29P-29P.
  • Hornby DP & Ford GC (1998) . Curr Opin Biotechnol, 9(4), 354-358.
  • Beesley AH, Hornby D & White SJ (1998) . J Physiol, 509 ( Pt 3), 629-634.
  • Pinarbasi E, Kan MS, Duran C, Ford GC & Hornby DP (1998) Substitution of the conserved phenylalanine in the S-adenosyl-L-methionine binding site of M.MspI with tyrosine modifies the kinetic properties of the enzyme.. Biol Chem, 379(4-5), 591-594.
  • Chapman NR, Kessopoulou E, Andrews PD, Hornby DP & Barratt CLR (1998) The polypeptide backbone of recombinant human zona pellucida glycoprotein-3 initiates acrosomal exocytosis in human spermatozoa in vitro. BIOCHEM J, 330, 839-845.
  • Beesley AH, Ortega B, Parker AJ, Hornby D & White SJ (1997) Quantification of ROMK mRNA expression in rat kidney by competitive polymerase chain reaction (PCR). JOURNAL OF PHYSIOLOGY-LONDON, 505P, 115P-115P.
  • Chapman NR, Kessopoulou E, Hornby DP, Cooke ID & Barratt CL (1997) The polypeptide backbone of recombinant human ZP3 induces acrosomal exocytosis in human spermatozoa. HUM REPROD, 12(5), S13-S13.
  • Whitmarsh AJ, Woolnough MJ, Moore HD, Hornby DP & Barratt CL (1996) . Mol Hum Reprod, 2(12), 911-919.
  • Austin N, Li Q, Hornby D & White S (1996) Renal and extrarenal localization of the RACTK1 K+ channel by immunofluorescence. JOURNAL OF PHYSIOLOGY-LONDON, 497P, P94-P95.
  • Henderson RM, Schneider S, Li Q, Hornby D, White SJ & Oberleithner H (1996) Atomic force microscopy used to image the inwardly-rectifying ATP-sensitive potassium channel protein, ROMK1.. KIDNEY INTERNATIONAL, 50(5), 1780-1780.
  • Austin N, Li Q, Hornby D & White S (1996) Renal and extrarenal localisation of the RACTK and ROMK1 K+-channel proteins. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 7(9), A0139-A0139.
  • Henderson RM, Schneider S, Li Q, Hornby D, White SJ & Oberleithner H (1996) . Proc Natl Acad Sci U S A, 93(16), 8756-8760.
  • Brewis IA, Clayton R, Barratt CL, Hornby DP & Moore HD (1996) . Mol Hum Reprod, 2(8), 583-589.
  • Li Q, Parker A, Hornby D & White SJ (1996) Differential expression of ROMK1 and RACTK potassium channel mRNAs in cell lines. JOURNAL OF PHYSIOLOGY-LONDON, 493P, P92-P92.
  • Pinarbasi E, Elliott J & Hornby DP (1996) . J Mol Biol, 257(4), 804-813.
  • HENDERSON RM, SCHNEIDER S, LI Q, HORNBY D, WHITE SJ & OBERLEITHNER H (1995) A ROMK1/GLUTATHIONE-S-TRANSFERASE FUSION PROTEIN IMAGED USING THE ATOMIC-FORCE MICROSCOPE. JOURNAL OF PHYSIOLOGY-LONDON, 489P, P90-P90.
  • LI Q, COPE G, HORNBY D & WHITE S (1995) IMMUNOCYTOCHEMICAL LOCATION OF THE POTASSIUM CHANNEL ROMK1 IN RAT-KIDNEY CORTEX. JOURNAL OF PHYSIOLOGY-LONDON, 489P, P93-P94.
  • Ford KG, Hornby DP & al Harrasy WS (1995) . Biochem J, 311 ( Pt 3), 901-904.
  • Hornby DP, Whitmarsh A, Pinarbasi H, Kelly SM, Price NC, Shore P, Baldwin GS & Waltho J (1994) . FEBS Lett, 355(1), 57-60.
  • Ford K, Waltho J & Hornby D (1994) . Biochem J, 298 Pt 3, 727-732.
  • Syed SE, Hornby DP, Brown PE, Fitton JE & Engel PC (1994) . Biochem J, 298 ( Pt 1), 107-113.
  • Baldwin GS, Kelly SM, Price NC, Wilson GW, Connolly BA, Artymiuk PJ & Hornby DP (1994) . J Mol Biol, 235(2), 545-553.
  • Soultanas P, Andrews PD, Burton DR & Hornby DP (1993) . J Mol Endocrinol, 11(2), 191-200.
  • Hornby D (1993) . FEBS Letters, 323(3), 295-295.
  • Taylor C, Ford K, Connolly BA & Hornby DP (1993) . Biochem J, 291 ( Pt 2), 493-504.
  • Ford K, Taylor C, Connolly B & Hornby DP (1993) . J Mol Biol, 230(3), 779-786.
  • Blackburn GM, Hornby DP, Mekhalfia A & Shore P (1993) . Collection of Czechoslovak Chemical Communications, 58(s1), 116-119.
  • Hornby DP (1993) . Methods Mol Biol, 16, 201-211.
  • Kusiak M, Price C, Rice D & Hornby DP (1992) . Mol Microbiol, 6(21), 3251-3256.
  • Dalton A, Hornby DP, Langston SP & Blackburn GM (1992) . Biochem J, 287 ( Pt 3), 871-879.
  • Hornby D, Ford K & Shore P (1992) . Methods Mol Biol, 11, 273-286.
  • Hornby D (1991) . FEBS Letters, 287(1-2), 226-227.
  • Sharrocks AD & Hornby DP (1991) S1 nuclease transcript mapping using sequenase-derived single-stranded probes.. Biotechniques, 10(4), 426-428.
  • Sharrocks AD & Hornby DP (1991) . Mol Microbiol, 5(3), 685-694.
  • LILLEY KS, HORNBY DP & ENGEL PC (1988) PURIFICATION, CHEMICAL MODIFICATION AND ANALYSIS OF PH-DEPENDENCE OF THE NADP+-DEPENDENT GLUTAMATE-DEHYDROGENASE OF ESCHERICHIA-COLI. BIOCHEM SOC T, 16(5), 876-877.
  • Hümbelin M, Suri B, Rao DN, Hornby DP, Eberle H, Pripfl T, Kenel S & Bickle TA (1988) . J Mol Biol, 200(1), 23-29.
  • HORNBY DP (1987) ISOLATION OF 3 COMPONENTS OF THE HYDROXYGLUTARATE PATHWAY FROM CLOSTRIDIUM-SYMBIOSUM. BIOCHEM SOC T, 15(6), 1039-1040.
  • HORNBY DP & BICKLE TA (1987) CHARACTERIZATION OF ECOP1 DNA ADENINE METHYLASE. BIOCHEM SOC T, 15(6), 1039-1039.
  • Sharrocks A & Hornby DP (1987) . Nucleic Acids Res, 15(20), 8564.
  • ENGEL PC & HORNBY DP (1987) A SIMPLE METHOD FOR THE CALIBRATION OF RECORDING FLUOROMETERS BY KINETIC MEANS IN THE STUDY OF NAD(P)+-DEPENDENT DEHYDROGENASES. BIOCHEM SOC T, 15(3), 386-387.
  • Rice DW, Baker PJ, Farrants GW & Hornby DP (1987) . Biochem J, 242(3), 789-795.
  • Hornby DP, Müller M & Bickle TA (1987) . Gene, 54(2-3), 239-245.
  • Rice DW, Hornby DP & Engel PC (1985) . J Mol Biol, 181(1), 147-149.
  • Hornby DP, Engel PC & Hatanaka S (1985) . Int J Biochem, 17(7), 851-854.
  • Hornby DP, Aitchison MJ & Engel PC (1984) . Biochem J, 223(1), 161-168.
  • Hornby DP & Engel PC (1984) . Eur J Biochem, 143(3), 557-560.
  • Hornby DP & Engel PC (1984) . J Gen Microbiol, 130(9), 2385-2394.
  • HORNBY DP & ENGEL PC (1983) . Biochemical Society Transactions, 11(2), 175-176.
  • Hornby DP, Engel PC & Hatanaka S (1983) . Int J Biochem, 15(4), 495-500.
  • Thompson MJ, Mekhalfia A, Hornby DP & Blackburn GM () . ChemInform, 31(5), no-no.
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Book chapters

  • Roberts RJ, Belfort M, Bestor T, Bhagwat AS, Bickle TA, Bitinaite J, Blumenthal RM, Degtyarev SK, Dryden DTF, Dybvig K , Firman K et al (2004) , Restriction Endonucleases (pp. 1-18). Springer Berlin Heidelberg
  • Whitmarsh AJ & Hornby DP (1994) , Highly Selective Separations in Biotechnology (pp. 163-178). Springer Netherlands
  • Ford KG, Whitmarsh AJ & Hornby DP (1994) (pp. 185-197).
  • Gjerde DT, Hanna CP, Hornby D & Bonn G () Wiley-VCH Verlag GmbH & Co. KGaA
  • Hornby DP () John Wiley & Sons, Ltd
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Conference proceedings

  • Dickman M, Rose JP, Marino MA & Hornby DP (2002) Analysis of the RNA component of human telomerase and its associated activity.. AMERICAN JOURNAL OF HUMAN GENETICS, Vol. 71(4) (pp 333-333)
  • Matin MM & Hornby DP (2002) A rapid, accurate and quantitative method for analysis of the methylation status of imprinted genes, using primer extension and IP RP HPLC.. EUROPEAN JOURNAL OF HUMAN GENETICS, Vol. 10 (pp 294-294)
  • Brewis IA, Chapman NR, Barratt CLR, Hornby DP & Moore HDM (1995) The signal transduction pathway of the acrosome reaction in human spermatozoa in response to purified recombinant human ZP3. HUMAN SPERM ACROSOME REACTION, Vol. 236 (pp 426-427)
  • Chapman NR, Hornby DP, Barratt CLR & Moore HDM (1995) The production and purification of recombinant human ZP3 from E-6coli. HUMAN SPERM ACROSOME REACTION, Vol. 236 (pp 404-405)
  • Barratt CLR & Hornby DP (1995) Induction of the human acrosome reaction by rhuZP3. HUMAN SPERM ACROSOME REACTION, Vol. 236 (pp 105-122)
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Teaching activities

Level 3 modules

  • MBB308 Molecular Systems Biology and Synthetic Biology (Module Coordinator)

Level 2 modules

  • FCP201 Molecules to Market (Module Coordinator)
  • MBB267 Molecular Bioscience 2B
Professional activities and memberships
  • 2015 Fellow of the Royal Society of Biology (FRSB)

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